| 00:01 | OK, folks. Um Welcome. As I expected several started spring break |
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| 00:10 | . So don't blame me. Um remember, don't come to school next |
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| 00:17 | . Uh There's no classes. So um do do uh don't make it |
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| 00:25 | work next week, do take do, do something fun next |
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| 00:29 | whatever that may be. Um So that point, uh that's kind of |
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| 00:35 | the nine weeks. So basically get another six weeks once we come back |
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| 00:41 | the end of the semester. um so we'll continue on with chapter |
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| 00:47 | , which is the end of the two stuff, which will finish up |
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| 00:52 | we come back and then uh the week on the 25th starting the third |
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| 01:00 | . And so um the uh so exams at the end of the |
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| 01:05 | So remember that, that scheduler opens Thursday, the 14th. OK. |
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| 01:12 | And you remember the, the new for that? Uh So anyway, |
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| 01:18 | uh the quiz, so this is one canvas quiz that uh you have |
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| 01:24 | uh 10 days, 10 days to . It's not due until the Monday |
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| 01:29 | the week we come back. And um smart work as well. Not |
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| 01:34 | due until 18th. So lots of for those. So, uh what |
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| 01:40 | ? So what we're gonna do today finish up viruses in terms of like |
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| 01:48 | the structure and um make up, up a virus and then get into |
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| 01:53 | cycles. Um We start with kind start with simple life cycles which involve |
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| 01:59 | bacterial viruses. And then when we back, we'll, we'll get into |
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| 02:04 | animal virus life cycles uh which are little bit more complicated only because they |
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| 02:12 | in a more complicated host cell host , right? Ear cells a little |
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| 02:17 | complicated than a bacterial cell. and as a result, the virus |
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| 02:22 | is a little, a little more by comparison. But uh we'll go |
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| 02:27 | all that. Uh So let's just look at um uh recap. |
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| 02:35 | So he went through definition of a , how to describe them a little |
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| 02:40 | about um a little bit about structure not completely. And so remember that |
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| 02:47 | number one thing is they're not OK. So I remember they do |
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| 02:51 | some cell properties, right? Like they can um evolve, they can |
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| 03:00 | um they do uh replicate but they only inside of a cell, |
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| 03:05 | Not, not outside of the They um they rely on the host |
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| 03:11 | most things. OK? But not we'll talk about a little bit about |
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| 03:15 | . Here in a second. So because we need a host, we |
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| 03:19 | them uh parasites. OK. Uh obligate because they are required to do |
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| 03:28 | . That's the only way they can . They're tied to that host |
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| 03:33 | OK. And of course, they their activities inside the cell, hence |
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| 03:38 | . OK. So the most, viruses had the most basic structure of |
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| 03:44 | protein covering what they call a Uh And the genome inside RN A |
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| 03:52 | , single or double stranded. That all viruses have that. |
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| 03:57 | We'll see that you can build on and have variations and additional things and |
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| 04:02 | forth. OK. Um Also know we're also gonna talk about thyroids and |
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| 04:11 | in a little bit. Those are viruses. OK? So think of |
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| 04:16 | is, that's why there's kind of categories here, the viruses, virus |
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| 04:20 | prions because these, these differ, don't have that this kind of a |
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| 04:26 | . OK. Uh They're simpler, fact. OK. Um And so |
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| 04:32 | in terms of, you know, um uh other like uh like |
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| 04:37 | cells can have different sizes and so . So can viruses, they can |
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| 04:40 | different uh shapes and uh lengths, and so forth. But they're mostly |
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| 04:47 | the nanometer scales, right? So than one micron, uh we'll see |
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| 04:53 | variations on that. But for the part, that's where they reside. |
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| 04:58 | um the uh all right, are , so, and then we looked |
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| 05:10 | a little bit of a basic life . So remember the part that all |
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| 05:15 | do, it's gonna be this, ? This part will vary, |
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| 05:26 | Not all viruses can integrate into a chromosome, but they'll all, you |
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| 05:32 | . And so it really begins or here with recognizing the host, then |
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| 05:37 | is inside the cell gets copied, , translated to make viruses, viruses |
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| 05:42 | . So that's, that's common to kind of virus. OK. |
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| 05:46 | there's gonna be variations in how this and, and done in different |
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| 05:52 | Um What they need from the hosts vary. Some come with their own |
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| 05:57 | , some do not, but they will need uh ribosomes, Trnas and |
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| 06:03 | to do protein symptoms. They don't that with them. OK. Uh |
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| 06:07 | of course, these other things. uh so again, remember they don't |
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| 06:11 | a metabolism, you can't say here's glucose, start respiring, they |
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| 06:15 | do that. OK. So, uh using the host for these |
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| 06:20 | OK. So remember though, always in mind that while doing this, |
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| 06:26 | ? The the effects on the host , right? Because the host cell |
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| 06:32 | getting its resources used to support this while it's replicating. So that means |
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| 06:39 | host cell suffers in terms of how it can grow and these kinds of |
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| 06:44 | . OK. We'll see that the especially with animal viruses and, and |
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| 06:49 | bacterial viruses, the whole cell can a whole spectrum of virus infects, |
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| 06:55 | cell. Boom. That's it. virus can just live inside the cell |
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| 06:59 | a long time before it does anything it, to everything in between. |
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| 07:04 | . That's especially true. Uh, animal viruses. They have so many |
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| 07:08 | types of um life cycles and variations they can do. OK. Um |
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| 07:17 | of course, those, those, know whether and those will have differing |
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| 07:22 | on the whole self and being killed to almost immediately to, to be |
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| 07:26 | to live a somewhat normal life to between. OK. Um All |
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| 07:35 | let's see. Oh, when we on this right host range and, |
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| 07:38 | tropism. So remember uh all that really about the interactions right between the |
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| 07:46 | and host, right? Um recognizing specific proteins, glycoproteins molecules on the |
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| 07:56 | many times what these are on the cell are already existing um receptors of |
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| 08:04 | types that the cell would use for functions. So one example is our |
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| 08:10 | have receptors for cholesterol, right? is part of our membrane in our |
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| 08:15 | . And so our cells take these and there are viruses that use those |
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| 08:20 | their way to get in. So very often is gonna be existing receptors |
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| 08:25 | of different types of viruses that use well. OK. But it's it's |
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| 08:29 | specific interaction though. OK. So Coronavirus recognizes, recognizes these specific receptors |
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| 08:37 | are present on cells in your in lungs. Ok. Uh But another |
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| 08:43 | type won't recognize that. So a virus which is also a respiratory infection |
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| 08:49 | flu virus will recognize other types of . Ok. Um Now remember the |
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| 08:56 | versus narrow, right? And in of host range and what I call |
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| 09:02 | specificity. The fancy name is Ok. So uh rabies virus is |
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| 09:09 | good way to remember this. So rabies can infect all different types of |
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| 09:13 | , right? Dogs, cats, , rats, mice, whatever. |
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| 09:17 | within that specific host, it can infect nerve cells, right? So |
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| 09:23 | a squirrel, a cat and a and a bat, they're only gonna |
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| 09:27 | nerve cells. So it's a very in terms of tissue specificity. |
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| 09:32 | Um But broad in terms of the of different types of animals, they |
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| 09:37 | infect. Ok. So viruses vary on that. So uh HIV has |
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| 09:42 | narrow host range and also a narrow specificity. Um The uh Ebola narrow |
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| 09:54 | , in fact, bats but uh humans but um broad tissue specificity in |
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| 10:01 | many different types of of tissue Ok. And um that's generally, |
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| 10:08 | was if I was gonna say a rule here is that most viruses do |
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| 10:14 | a narrow tissue specificity, ok. either cells to the respiratory system. |
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| 10:21 | a if it's a respiratory virus or system. So for the most |
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| 10:25 | they're narrow, it's Ebola is kind one of those types, uh, |
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| 10:30 | can infect different tissues and there's, some others, right? But those |
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| 10:34 | do that tend to be pretty right? Because they, they can |
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| 10:39 | different tissue types in your body. a lot to have to overcome. |
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| 10:44 | . It's no wonder that Ebola has a very high mortality rate. |
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| 10:50 | , if you contract Ebola it's upwards 90% mortality, only 10% chance of |
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| 10:56 | . And that's, and it's really of different tissue types, it can |
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| 11:00 | . OK. So uh so all this um is all about this |
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| 11:06 | . OK. What does it recognize ? Um All right, any questions |
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| 11:12 | that? OK. So let's look this question. So we'll get into |
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| 11:15 | little more about structure of a So let's look at this question |
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| 11:20 | So the naked virus is lacking or what? So remember as with any |
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| 11:29 | these kinds, these kinds of if you don't see an answer, |
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| 11:34 | , then that's your answer, Yeah. OK. Speed this up |
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| 11:53 | little bit here. So, all . Thank you now. Mhm |
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| 12:13 | Um So the thing that's missing is envelope? Yeah, it's envelope. |
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| 12:22 | you don't see envelope listed here. it's uh that on the lope. |
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| 12:31 | . Um All right structure. So granite, the classification here is kind |
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| 12:36 | based on symmetry. So uh s viruses um you know, you can |
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| 12:42 | it, cut it in half and have identical halves, right? That's |
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| 12:45 | . So uh very often these types a um this icosahedra that's a 20 |
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| 12:53 | uh geometric structure. Uh So remember caps is made up of capsule |
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| 13:01 | And so, but don't think every uh in this diagram, every |
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| 13:06 | block right is a one of those , the capsule. OK. So |
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| 13:12 | , this will have lots of capsule . But in terms of being different |
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| 13:19 | , in terms of structure, this has three, right? 123, |
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| 13:23 | one has four I'm sorry, uh . So they have um on the |
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| 13:29 | the surface. So three different caps proteins on the surface, right? |
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| 13:34 | so um but remember that the genome a virus is pretty small. So |
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| 13:39 | can't have a lot of genes for things. So you kind of consolidate |
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| 13:44 | you you, you limit your different types to maybe 3 to 4 |
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| 13:49 | 5 in that range and then they of assemble the form of structure. |
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| 13:54 | . Um The oops sorry, the envelope viruses. So this this right |
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| 14:01 | as shown would be a naked right? It's just a capsule. |
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| 14:07 | if it's doesn't has an envelope, you're gonna have a layer around |
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| 14:11 | OK? As you see here, is the caps structure, there's a |
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| 14:17 | there and surrounding it is an OK. So um so the envelope |
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| 14:22 | from the host cell, right? this is basically a lipid bilayer coming |
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| 14:27 | the, that that originates from the cell membrane. So as the virus |
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| 14:32 | assembled and exits the cell, that wraps around it. OK. But |
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| 14:39 | the course of the infection, as see, I'm talking about this uh |
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| 14:44 | when we come back. But uh the virus is being um replicates, |
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| 14:49 | genome makes vowel proteins, many of proteins then go to the surface of |
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| 14:55 | host cell. And then as the exits, it gets the envelope plus |
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| 15:01 | viral proteins on the surface that it's to have, right? So that's |
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| 15:06 | of how that works. And so the envelope is a feature as far |
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| 15:14 | I know of only animal viruses, ? Because uh typically with bacterial |
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| 15:22 | uh they don't have an envelope, have uh just a capsid uh but |
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| 15:28 | don't have some other different structures. , envelopes are typically only a feature |
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| 15:31 | animal viruses. OK? Um uh let's see here. OK. |
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| 15:38 | glycoprotein spikes, OK. So these a feature of many viruses. Um |
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| 15:44 | may not be uh so prominent and like like these are OK. But |
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| 15:52 | these are gonna be um you anything on the surface generally is about |
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| 15:56 | the host attaching. Uh it it also be for help helping in in |
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| 16:02 | from the cell as well, So that's kind of what the features |
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| 16:06 | of these surface viral proteins. Um, filamentous types. So, |
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| 16:14 | types are gonna be like strings like . Um, they can, uh |
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| 16:19 | will have a, can have a on as well as you see |
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| 16:23 | Ok. Um Tobacco mosaic virus uh have the capsule has, doesn't have |
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| 16:30 | uh envelope, sorry, but it have the capsules here. You see |
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| 16:33 | blue red is the genome. Uh it will be a long kind of |
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| 16:38 | strand. OK. The um tailed , depending on the textbook, they |
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| 16:45 | these different things. Uh some can call these uh complex viruses because they're |
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| 16:50 | of a combination of forms. So see the the geometric caps in |
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| 16:56 | but then it has in addition to um these other structures. So this |
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| 17:01 | of tube here is a um will . So when this thing attaches to |
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| 17:08 | cell and this is a typical for bacterial virus, OK. So it |
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| 17:14 | a whole cell sitting here. It , it will recognize the whole hotel |
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| 17:22 | tail fibers. OK. So that's of what rests on the cell. |
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| 17:28 | this part comes down and it will compress and pressure shoots the genome into |
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| 17:37 | cell, right. So the genomes here and it will enter the cell |
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| 17:43 | all this will stay behind. Stays outside the cell. And that's |
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| 17:49 | for bacterial virus. Genome comes Everything else stays out. OK. |
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| 17:56 | um so asymmetrical viruses are not so viruses. You can, you can |
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| 18:02 | identical halves of the virus, more kind of think of it as |
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| 18:09 | , a roundish roundish blob ish OK. Not completely symmetrical but kind |
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| 18:18 | some are more blobby than others. . Uh COVID is like this flu |
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| 18:23 | has this shape. Um uh And they're more kind of amorphous in a |
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| 18:29 | , not a uniform circle. Uh But aside from the shape, |
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| 18:34 | know, they do have the typical , right? Uh This one has |
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| 18:37 | envelope flu virus has an envelope, have the capsid, then you have |
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| 18:41 | thing called the nucleo protein. We're gonna talk about that here. |
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| 18:48 | . So um Coronavirus has that as . And so for Coronavirus, we |
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| 18:55 | the envelope structure here, right? Despike proteins. OK? And then |
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| 19:02 | this genome. OK? This is A genome. So you don't see |
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| 19:08 | little house, that's the caption, ? Something like this. All |
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| 19:14 | This is what we've been seeing. . This one uh has its genome |
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| 19:22 | of covered with a capsule that looks this. So this is what we |
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| 19:28 | nucleo N because it, it attaches the nucleic acid in this case, |
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| 19:33 | A. OK. So these are and this is in essence the cap |
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| 19:39 | if you will. OK. So not a structure like this, it's |
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| 19:44 | attached to the chrome to the to genome. OK? And in that |
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| 19:49 | serves the same purpose it, it , it, protects the genome. |
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| 19:54 | . So, um, but that's a variation, you'll see. |
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| 19:57 | even the, um, going back , even the, uh flu |
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| 20:03 | it does have a capsule in but it has that as well on |
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| 20:06 | genome. Those nucleocapsid proteins. So, actually has both, uh |
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| 20:13 | has just the one type. Um, and you'll see this variation |
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| 20:19 | , with different viral types. Um, what is it, what |
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| 20:25 | it mean to have one over the ? I don't know if it |
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| 20:27 | I don't think there's, it's known the significance is of that, but |
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| 20:31 | you know, it is a way starting to protect the, protect the |
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| 20:36 | . OK. Uh OK. So just talking only in general terms about |
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| 20:43 | genomes, right? Just a couple things to point out. So one |
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| 20:47 | , the size is based on the of the virus, right? Smaller |
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| 20:51 | , smaller genome can accommodate fewer right? Larger spectrum. So something |
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| 20:56 | a poliovirus is pretty big in terms genome sizes for viruses, it'll have |
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| 21:02 | , more genes. OK. Um types of genes you find and you |
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| 21:07 | need to know this uh memorize but the types of genes you find |
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| 21:13 | of course, are are virus specific , right? So what is |
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| 21:16 | what's the it the virus needs a to replicate? But even having said |
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| 21:23 | the virus does have to contribute some things to it, right? Because |
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| 21:30 | virus is made up of virus specific , right? So you have capsid |
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| 21:36 | are gonna be things that are encoded the genome. Um you know the |
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| 21:40 | spike proteins and things on the surface are part of recognition are viral. |
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| 21:45 | that's gonna be coded for. And may be enzymes like you see here |
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| 21:50 | are involved in the assembly and the the um exiting of the virus. |
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| 21:56 | th those those will be virus So you'll have some of those in |
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| 22:00 | . And so again, anything that help the virus replicate and exit the |
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| 22:05 | or um um uh recognize, attach the cell or be be part of |
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| 22:13 | catch. Those are all gonna be specific uh structures. OK? And |
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| 22:19 | when we talk about uh dimensions are segmented, OK. So most viruses |
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| 22:28 | will have a genome, something like . OK? It's one piece, |
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| 22:34 | ? One piece. And um that's called non segmented. OK? You |
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| 22:41 | the one thats what flu virus OK. So you see eight different |
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| 22:46 | . Wow, eight different segments. . And uh that's a genome, |
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| 22:52 | segments. OK. And so what enables and, and of course, |
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| 22:58 | viruses, all viral types can, mutate, of course, and, |
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| 23:03 | change. Um uh and also um for like say for a flu virus |
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| 23:11 | , more than one flu virus can the same cell. OK? And |
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| 23:17 | and so can other viral types. . And what that can do is |
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| 23:21 | can have recombination of genomes in in the cell being infected. |
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| 23:28 | So, especially with the flu virus has segments, these segments can |
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| 23:33 | OK. And so when we look , for example, the there's different |
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| 23:38 | of flu viruses, OK. And designated by the, OK. The |
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| 23:52 | ones are involved in um attachment and getting into the host. The |
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| 23:58 | ones are actually involved in exit. . But they, but they |
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| 24:03 | they produce an immune response in the . Ok. Um And this is |
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| 24:09 | changes, you know, because flu vary from year to year because the |
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| 24:14 | is changing and, and the changes particularly in those in those outer ancient |
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| 24:19 | proteins. OK. And so V flu virus originated in uh aquatic, |
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| 24:26 | , birds of various like ducks, of wild, uh wild aquatic |
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| 24:33 | And then, uh, then also the jump into uh domestic birds, |
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| 24:42 | chickens, um uh domestic ducks, like that and then into swine, |
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| 24:49 | ? Because there's swine flu as And so you can see the evidence |
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| 24:54 | that in the genomes of viruses. this is kind of, you |
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| 24:57 | simplifying it for you. But uh , they're, they're color coded here |
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| 25:02 | the origins from the various bird species swine. OK. And so, |
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| 25:09 | , and of course, one of forms of balance between humans OK. |
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| 25:15 | so, you know, and all involves is getting changes in these proteins |
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| 25:20 | the surface such that they, such they recognize um will recognize this receptors |
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| 25:27 | a, on a human cell or virus re respiratory cells, right. |
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| 25:32 | uh so they find the right change the right key to fit the lock |
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| 25:36 | they get in right and cause So, uh so these of course |
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| 25:42 | evolve uh year to year, of . And so we um we sequence |
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| 25:49 | the, so we have a huge of, of information about the uh |
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| 25:56 | sequence of the, of this And we look to see your year |
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| 26:01 | changing, right? So specifically looking changes in these outer proteins, |
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| 26:07 | then you try to predict OK, , what can we, what can |
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| 26:11 | um put in our vaccine to uh ? You know, maybe, maybe |
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| 26:16 | it'll morph into this form and that's of how we'll formulate our vaccine. |
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| 26:22 | so a vaccine will be a combination different of these spike proteins in |
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| 26:28 | And so the idea is that uh know, some years, it's |
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| 26:31 | some years, it's not so And so it's all because you can |
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| 26:34 | absolutely nail down how it's what form will evolve into. You can kind |
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| 26:39 | just make a educated guess. um but that's, that's kind of |
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| 26:44 | they do that. OK. Um general rule is, and this is |
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| 26:50 | RN A virus. RN A viruses more prone to mutating because there's really |
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| 26:58 | repair systems to fix mistakes. So we have repair systems without, |
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| 27:04 | have DNA. Right. And, so D nav, uh D nav |
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| 27:11 | A DNA viruses, uh can have ability to have mistakes fixed because of |
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| 27:17 | because as humans have those capabilities. um ARN viruses can have more mutations |
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| 27:24 | they can evolve uh a little bit in some cases. OK? Um |
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| 27:30 | again, the, the changing is about acquiring changes in the genome to |
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| 27:36 | change these outer proteins because that will how um the body sees it, |
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| 27:43 | ? So it was, if it , if it was a new form |
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| 27:46 | infectious, but the body hasn't seen before, then it, then, |
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| 27:49 | you're, then you're more susceptible. anyway, so you, you |
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| 27:52 | you try to come up with vaccines can hopefully deal with that variation. |
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| 27:58 | ? Uh It's a, again, , it's, it's always a constant |
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| 28:02 | battle. OK? Um Any questions genome structure thing? OK. So |
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| 28:11 | uh switch gears a bit and look prions and thyroids. All right. |
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| 28:17 | as you read these, uh you wanna pick the one, there's |
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| 28:23 | true statement, the whole thing has be true. It could be |
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| 28:28 | that some of these have half of right, half of it's wrong. |
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| 28:32 | just make sure the whole thing is . OK. OK. Let's |
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| 29:18 | So we'll flip ahead. We're gonna this question here again. OK. |
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| 29:27 | let's um move ahead. So we'll with prions first. So pri uh |
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| 29:33 | , excuse me, vids, so . Um So the, the neither |
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| 29:39 | nor, nor prions uh well, with prions, it's the um mad |
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| 29:45 | disease. Ok. Um That's the human disease caused by a prion and |
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| 29:54 | chances of you catching that are next zero. There haven't been any cases |
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| 29:58 | that in. I, I don't how many decades. Ok. So |
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| 30:03 | I was gonna say was you, , you don't need to worry about |
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| 30:05 | or prions as causing you an Ok. Um What's unique about these |
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| 30:12 | things is that they are basically each infectious molecule. That's it. One |
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| 30:19 | an RN A vy roids and one's protein and that's essentially the, the |
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| 30:25 | in terms of structure. There's nothing to it than an RN A for |
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| 30:29 | vid, a protein for prime. it. Ok. So they're not |
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| 30:33 | because they don't have the typical virus . A protein coat a genome. |
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| 30:39 | don't have that. Ok. So why they're kind of their own |
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| 30:43 | Ok. Um Thyroids are a problem many, not many, but for |
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| 30:50 | number of crops, particularly potatoes. That's probably the most well studied. |
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| 30:56 | And so RNAs of course, aren't stranded like DNA, but they can |
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| 31:03 | these secondary structures, right? It's all complementary base a AUGC, |
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| 31:09 | And so, and that's secondary structure important for their functioning. OK. |
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| 31:14 | what do they do? So they uh they um combined co again, |
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| 31:35 | base pairing. So you may have message an MRN A by the |
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| 31:39 | for example. And this RN it's give it the shape here, |
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| 31:49 | ? And this would be the um , it could just buying complementary base |
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| 31:58 | to AM RN A and that in can block a ribosome from translating |
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| 32:04 | OK. So that's how it can uh gene expression. OK. Um |
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| 32:11 | , it replicates itself by simply using host or a pli to make |
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| 32:17 | OK. Um How it's transmitted to plants. Uh I don't know that |
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| 32:25 | known, but it could be through seeds are formed. Perhaps. Um |
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| 32:32 | if it's carried from plant to it would likely have to be some |
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| 32:37 | of a, I would guess uh kind of insect carrying it from plant |
|
| 32:41 | plant. Uh because plants generally aren't to penetrate. And so usually it's |
|
| 32:46 | , a vector of some sort that a, like a, an insect |
|
| 32:49 | some sort that does that. Uh But anyway, so, you |
|
| 32:54 | , yeah, the uniqueness here, an infectious piece of RN A is |
|
| 32:58 | it is. OK. No human are known to be caused by these |
|
| 33:03 | . OK. Now, the prion uh again, infectious protein. All |
|
| 33:10 | . So that, and that's There's no other structures associated with |
|
| 33:13 | The um so mad cow disease, was kind of a bit of a |
|
| 33:19 | back in the eighties, but that really confined to England. Had, |
|
| 33:25 | some reported cases of this. Uh was one fatality in the US that |
|
| 33:31 | from a person who had come over England. So, uh I'm not |
|
| 33:36 | of any fatalities of this in the . But um it was discovered, |
|
| 33:41 | think in sheep, that's what scrapey to. This is what they called |
|
| 33:45 | in sheep. Um Apparently you can it if you're one of these tribes |
|
| 33:50 | the remote areas that practice cannibalism, can get it that way. Um |
|
| 33:56 | you know, if you do catch typically from um from contaminated meat, |
|
| 34:02 | ? Um Thing about this disease, a very slow progressive disease, |
|
| 34:08 | You don't even know you've ingested infected because you won't, you experience symptoms |
|
| 34:14 | it could be years, you before you experience any symptoms. |
|
| 34:18 | Uh And, and there is no for it. So if you do |
|
| 34:21 | symptoms, that's, you know, much it. But, you |
|
| 34:25 | it is a slow progressing illness. And so the uh there is some |
|
| 34:33 | to support that there may be a component. So apparently it can be |
|
| 34:38 | , I think they've traced some families generations have contracted this. Uh But |
|
| 34:42 | don't know how extensive that is, there is some evidence for that. |
|
| 34:46 | Now what? So, so the about this is there is a normal |
|
| 34:53 | of the protein, right? And part of your body, it um |
|
| 34:59 | a molecule in your cells, it's the membrane. OK? And you |
|
| 35:04 | uh a good portion of it in uh nerve cells in your central nervous |
|
| 35:08 | . OK. Now, what the form does? There's been a lot |
|
| 35:13 | debate. Uh Strangely enough, they it has something to do with copper |
|
| 35:20 | of all things. OK. So they know that if it becomes this |
|
| 35:26 | form, which is the normal, , it is all about the |
|
| 35:29 | OK. So you can see the here are these alpha heli helices. |
|
| 35:35 | the blue are kind of those beta if you remember your protein structure. |
|
| 35:40 | they have no forms uh acquire a of these um have this kind of |
|
| 35:45 | sheet structure, OK? And less . So, in any case, |
|
| 35:50 | so, ingestion of these normal forms through the 10 of meat can induce |
|
| 35:57 | formation of uh from normal to So it kind of looks something like |
|
| 36:02 | kind of simplistic, but you'd have prion form that can attach to a |
|
| 36:09 | form and that in itself produces the this abnormal form confirmation, right? |
|
| 36:17 | this uh keeps occurring as these ba the the mi uh shapen ones by |
|
| 36:24 | correctly shaped ones to change them into prion. And again, this process |
|
| 36:29 | over several years and the damage accumulates the cell cell dies and then those |
|
| 36:37 | can then be released and are taken by other cells and continues the |
|
| 36:42 | Ok. So what happens to a cell just quickly go, I'll come |
|
| 36:47 | to this. This could be a cell here. The green ones are |
|
| 36:52 | normal forms of the prions. Red are the misshapen ones. And so |
|
| 36:56 | they bind together, uh converting the into the red forms, uh these |
|
| 37:02 | in the cell and of course, damages function of the neuron. The |
|
| 37:07 | dies. Ok. And what's left because nerves don't s nerves to the |
|
| 37:13 | nervous system don't generally regenerate themselves. , um you're left behind holes in |
|
| 37:19 | brain tissues. This is a slice brain tissue of I I assume an |
|
| 37:24 | that's been infected with this uh prion protein and you see the results. |
|
| 37:30 | these these hole basically holes in the tissue. So that creates a very |
|
| 37:35 | texture to the brain. Ok. , um and so encephalopathy refers |
|
| 37:42 | you know, pathology of the brain . So it becomes very uh |
|
| 37:47 | obviously severe neurological impairment, motor function stuff like that uh worse as it |
|
| 37:56 | . Ok. Um Apparently these things also, I guess because of their |
|
| 38:00 | and how they fold, they're very to temperature chemicals and things. |
|
| 38:05 | um, you know, if you , although I don't know how, |
|
| 38:08 | know it, that you're eating contaminated , I, I cook the heck |
|
| 38:13 | of it. Right. If you're eat it. But, uh, |
|
| 38:15 | don't, I don't see that that's really a problem in the US. |
|
| 38:20 | . Or, I don't even know much elsewhere in the world is a |
|
| 38:22 | . But again, like with uh , the uniqueness is the, in |
|
| 38:27 | , it's an infectious molecule basically. . Um OK. Uh Let's try |
|
| 38:36 | one again. OK. If you like changing your answer or not, |
|
| 38:41 | uh while you're looking at this, there any questions, thyroids or |
|
| 38:51 | Anything? So, remember they're not of the other, other main things |
|
| 38:55 | they are not viruses. OK? their own unique thing. OK. |
|
| 39:39 | . Let's see here. Yeah, , it's, it's the, everybody |
|
| 39:46 | much answered it right the first So um so yeah, the only |
|
| 39:50 | fitting here is completely correct is So uh this one's uh um com |
|
| 40:02 | wrong. All right. There's no in a prion thyroids or RN |
|
| 40:07 | Um That's wrong. That's wrong. ST vs can, of course, |
|
| 40:14 | can both replicate, that's wrong. There, this is wrong. Uh |
|
| 40:23 | wrong. So uh well, they, they don't, of |
|
| 40:25 | But uh so yeah, d is only completely correct statement here. So |
|
| 40:31 | get into a little bit about, look at this question and we're gonna |
|
| 40:34 | about um classification of viruses but more about um because it can be a |
|
| 40:43 | bit confusing is the nature of, uh RN A viruses. OK. |
|
| 40:50 | is why I put this question up it can be as we go through |
|
| 40:55 | more when we come back from uh their life cycles could be a |
|
| 41:00 | bit uh may not make sense, there's a reason why they do what |
|
| 41:06 | do in the order, they do in China. So it's kind of |
|
| 41:10 | do a little bit of explanation on . Uh After we do this question |
|
| 41:27 | . OK. So we're asking about , what can they, so different |
|
| 41:35 | of RN A viruses and they use genome for different purposes depending on the |
|
| 41:40 | they are. OK. So, . So yeah, they can be |
|
| 41:52 | the above, right? So that's your, we call plus on |
|
| 42:01 | virus. There is a minus RN virus and this is a retrovirus. |
|
| 42:12 | . So um well, let's look , so, classification, right? |
|
| 42:18 | had a question last time about what the things you can look at to |
|
| 42:25 | viruses? You know, some of pretty obvious, right? You can |
|
| 42:28 | at, you know, what's the genome RN A DNA? What's the |
|
| 42:33 | does it have an envelope or Does it have uh uh with the |
|
| 42:38 | uh symmetry? Uh and so So, um generally, the classification |
|
| 42:45 | used this Baltimore system is uh based really the genome number one. All |
|
| 42:53 | . Is it DNA RN A? is it double or single stranded? |
|
| 42:58 | then uh it's the route to get the MRN A? So I would |
|
| 43:05 | this box. OK. Knowing that plus RN A is the MRN |
|
| 43:14 | OK? And being an MRN A you can be translated. So ribosome |
|
| 43:20 | pop on this and start translating. ? Um We call it the sense |
|
| 43:26 | A. So whether it's DNA or A, there's always a plus sense |
|
| 43:32 | and there is a minus anti sense . OK. So, so the |
|
| 43:39 | of getting to the MRN A. , it varies depending on how |
|
| 43:42 | how you get there varies depending on viral type. OK? Of |
|
| 43:47 | it's important because remember this is gonna needed to make the captured, |
|
| 43:54 | And the other viral components uh because gonna assemble all these things and then |
|
| 43:58 | gonna put a genome in, So let's take a detour for a |
|
| 44:05 | . OK? And look at OK. So um the language of |
|
| 44:16 | of nucleic acids, like when you about nucleic acids, there's certain things |
|
| 44:20 | are a constant, right? You that there's gonna be a five prime |
|
| 44:26 | three prime end, right? This all just relates to the, the |
|
| 44:29 | of nucleotide and putting them together, ? So there's a five prime and |
|
| 44:33 | prime end, it's complementary, Basically, they are complementary to each |
|
| 44:39 | . And so, so the they're identical, right? This, this |
|
| 44:44 | uh we're going to um uh one always designated the plus strand. The |
|
| 44:50 | is the minus strand. OK. so the um the uh and so |
|
| 44:57 | same rules apply whether it's DNA which is what our chromosomes are or |
|
| 45:02 | it's DNA RN A, right? happens during transcription, right? Our |
|
| 45:07 | , one of our DNA strands are strand is, is what we're going |
|
| 45:12 | do. We're actually gonna copy the strand. OK? Because it is |
|
| 45:17 | other thing, remember when you copy strand, you're gonna copy the |
|
| 45:23 | right? So if we copy we're gonna copy the plus, we're |
|
| 45:26 | make, we're gonna make a plus by copying this one. OK? |
|
| 45:33 | that plus strand will be orientation, ? Plus a GC, you, |
|
| 45:43 | it's going to be our name, ? Mr A? And we can |
|
| 45:48 | this is identical to that, And that's so because we're copying the |
|
| 45:57 | we call the template strand template or this is a coding strand. Ah |
|
| 46:06 | . This is the coding strand here the South, the way coding |
|
| 46:13 | So that contains the essential information that the information to make a protein. |
|
| 46:19 | we don't, we don't translate we translate RN A. So we |
|
| 46:23 | to make an RN A copy of and that's how it's done. |
|
| 46:26 | we copy the template because we know the minus strand gives us a |
|
| 46:31 | right? That's gonna be, that's to the DNA. Obviously, the |
|
| 46:36 | cells are in place of thymine. . So that's how we now have |
|
| 46:41 | , the coding information in the form RN A, right? Um |
|
| 46:46 | So our, our name that you see in eukaryote prokaryotes, you see |
|
| 46:53 | in viruses, OK? Um Because except viruses are DNA, right? |
|
| 47:00 | they're gonna be DNA, either DNA in their chromosome or when they're doing |
|
| 47:06 | , right? But you don't see . OK? And um so, |
|
| 47:13 | again, so for all three of groups, right? The same rules |
|
| 47:16 | . One's a plus one's a it's all complimentary five times three prime |
|
| 47:20 | just the lingo of, of nucleic , right? And so with RN |
|
| 47:27 | viruses, right, we can have plus single stranded RNA virus, |
|
| 47:32 | Which would be that OK. And can obviously have a minus RN A |
|
| 47:38 | . OK. Which would be something this, right? So when these |
|
| 47:43 | viruses then begin to replicate, Uh And then also translate OK into |
|
| 47:52 | , we're gonna copy OK. And OK. So you might be |
|
| 47:57 | having just learned that the plus strand for reference, right? Plus RN |
|
| 48:07 | uh come on plus R A equals . OK. So, um are |
|
| 48:23 | , so um So the MRN A be translated. So the cluster and |
|
| 48:28 | go, OK. Well, that's MRN A, that's all it |
|
| 48:32 | . It doesn't need to do anything , right? It can, it |
|
| 48:35 | express proteins from this and it's on way. OK. Well, |
|
| 48:42 | OK. Because, yeah, it , it could certainly express pro viral |
|
| 48:47 | with that. But what else is ? Right. The missing part |
|
| 48:52 | you only gotta think of the end here. This is the end |
|
| 48:56 | OK? In a basic simplified OK. Here's our virus. |
|
| 49:05 | Here is host cell. OK. gonna come out? Multiple viruses? |
|
| 49:17 | . Well, OK. Yeah, can make proteins with that but I |
|
| 49:22 | to put genomes and all these capsules making, right? So we're gonna |
|
| 49:27 | to make more copies of this right that genome because that's what the virus |
|
| 49:33 | , that's infecting, right? So are we gonna do that? |
|
| 49:39 | OK, we are going to, right, do this. Let me |
|
| 49:48 | if I can get this off of screen here. OK. I, |
|
| 49:53 | do it this way. OK. . There we go. What we're |
|
| 50:01 | do is copy that. We're gonna that into this. Now, it |
|
| 50:09 | be super simple, super easy as . If life would allow us to |
|
| 50:14 | copy that into a plus strand, happen, doesn't happen on planet |
|
| 50:20 | right? Maybe somewhere in some other where things work differently. Maybe it |
|
| 50:26 | but it doesn't. Right. Because copy it into a complementary strand. |
|
| 50:32 | . So we can't do that. right. So what we do is |
|
| 50:43 | oh goodness. Uh Here we I'm playing. OK. So what |
|
| 50:47 | gonna do is um OK. Go it. This thing will not let |
|
| 50:56 | erase this. Stupid. OK. right. So what we're gonna do |
|
| 51:04 | we're gonna make lots of copies of plus strand into minus. OK? |
|
| 51:11 | we're gonna take all those and copy into plus strands. OK? So |
|
| 51:16 | other thing here is it's a numbers . So if we have just one |
|
| 51:19 | two viruses infecting, you know, need that more than just that, |
|
| 51:25 | just one template, right? If wanna make lots of protein, you |
|
| 51:28 | , rather quickly. So the way get there is to make copies, |
|
| 51:33 | we can't go directly from plus to , we have to know what, |
|
| 51:38 | nucleic gasses let us do. Which is to make the complementary |
|
| 51:41 | which is negative, copy that into positive. OK. Um And now |
|
| 51:47 | get two things. We get expression the bowel proteins to make our capsules |
|
| 51:53 | we can stuff those caps with our . OK? And so each of |
|
| 51:59 | will have a captain around it. now we've completed the viral cycle and |
|
| 52:06 | can exit the cell and infect more . OK? Similarly, with the |
|
| 52:10 | RN A virus, we need lots stuff, right? So first we |
|
| 52:15 | to, we can't translate that at . We have to make that into |
|
| 52:18 | plus string. So we do it that. Now, we can translate |
|
| 52:22 | proteins, make our capsules. And then we gotta make negative minus strands |
|
| 52:29 | that's what our virus is, It's one of these, right? |
|
| 52:33 | then we do that, then we make a little cap house around |
|
| 52:37 | Right now. We've got a complete . It connects it and affect more |
|
| 52:42 | . So you just, it's, convoluted because we're just following the rules |
|
| 52:47 | nucleic acids. OK? Uh If is not because these are RN A |
|
| 52:51 | , it's just, that's the way stuff works. OK? So with |
|
| 52:58 | this other type, it's completely right? Retroviruses, right? So |
|
| 53:04 | uh have a plus single RN OK? But what they, their |
|
| 53:09 | is to take that and to copy the name. OK. So |
|
| 53:15 | you see it's the same rules, right, plus strand of R and |
|
| 53:24 | , we copy it into DNA. a minor strand, right? And |
|
| 53:28 | it actually uses um host DNA polymerase make the complimentary copy. OK. |
|
| 53:38 | it has to do that because it into the host chromosome, right? |
|
| 53:42 | if you're gonna do that, you to be DNA double stranded to do |
|
| 53:46 | . OK? And so that's a from these two other groups. |
|
| 53:52 | So again, it's, it's literally , you know, this is how |
|
| 53:56 | has to happen, right? it's what happens in us. You |
|
| 53:59 | , when we copy a copy the strand here we are. Uh I'm |
|
| 54:06 | copy that into um A plus RN and that's, you know what gets |
|
| 54:12 | . So uh it's nothing different than what happens in us. OK? |
|
| 54:16 | any living thing. OK. the other thing here is that this |
|
| 54:22 | of copying RN A into RN A everything that's happening here is all this |
|
| 54:32 | all, this is all RN A but, right? There's no DNA |
|
| 54:40 | in any of this when it's the A virus of these two types doing |
|
| 54:45 | thing. OK? No, OK. So eu periodic systems or |
|
| 54:51 | bacterial systems do not copy RN A RN A, right? We don't |
|
| 54:58 | that. The only copying we do RN A is from DNA, DNA |
|
| 55:02 | RN A, right? Um So of this type um have to have |
|
| 55:10 | own enzyme to do this, So what we have is what's called |
|
| 55:17 | DNA dependent rnap Premera, right? what does our transcription, what these |
|
| 55:25 | have is called an RN A dependent RN A lyra. OK. And |
|
| 55:31 | that's um that let's go back this . That is what's abbreviated here. |
|
| 55:44 | Right here, this enzyme, So it's a virus specific enzyme again |
|
| 55:50 | copy RN A to RN A. And so we just looked at so |
|
| 55:56 | double stranded group I didn't mention, , you know, it's gonna, |
|
| 55:58 | gonna follow the same rules, right? So they're, they're um |
|
| 56:04 | copy as well to produce transcripts and into protein. Um We have the |
|
| 56:10 | stranded plus group we just saw and our Mrnas plus strands and then this |
|
| 56:18 | here um into, into there. remember that what's not shown here is |
|
| 56:25 | then go from here, but the enzyme RP to a minus strand because |
|
| 56:33 | what we're gonna need those genomes to into our, our capsules. |
|
| 56:38 | So, um again, it's just uh nucleic acid rules here. |
|
| 56:44 | And the last one, the retrovirus copy DNA uses host prema to get |
|
| 56:52 | uh double strand. So when it's integrated into the host chromosome, it |
|
| 56:57 | actually in that state transcribe and it make viruses. So the retrovirus, |
|
| 57:03 | talk about that when we come but it's a unique one in that |
|
| 57:07 | can um sit in the chromosome but carry out replication of viruses as |
|
| 57:13 | OK. Um So yeah, we will revisit all this or get |
|
| 57:19 | animal virus life cycles again. So just kind of wanted to bring it |
|
| 57:24 | now. So you kind of get to it and you kind of have |
|
| 57:27 | absorb this to kind of, you , the whole plus the minus the |
|
| 57:31 | thing. OK? But it's, it's not kind of any kind of |
|
| 57:35 | . It's, it's, it's what when you're dealing with the cle |
|
| 57:39 | OK. Um, any questions about ? OK. All right. |
|
| 57:47 | uh, let's go forward here OK. Don't memorize this table. |
|
| 57:53 | only bring it up just to show some representative types that you're familiar |
|
| 57:57 | So, in these, uh DNA , so things like, uh, |
|
| 58:02 | HPV, uh very common STD, , can cause cervical cancer, uh |
|
| 58:09 | viruses in this group. Um It's type that can uh both of those |
|
| 58:14 | and HPV are types that can integrate the chromosome. Um The among the |
|
| 58:21 | A viruses, many, many human caused by RN A viruses of various |
|
| 58:26 | . Uh rabies COVID flu mumps, , West Nile, which is, |
|
| 58:33 | is endemic in this part of the uh around Houston and East Texas. |
|
| 58:39 | So lots of them in that group those groups. Uh So the one |
|
| 58:43 | retrovirus, of course, the uh oddball here is this group per |
|
| 58:51 | They're kind of a variation of retrovirus that. They, they have |
|
| 58:57 | But um they have to reverse transcribe RN A into, back into |
|
| 59:07 | OK. And uh that's how they their genome. OK. It's a |
|
| 59:13 | bit, a little bit different. . The one significant one there |
|
| 59:18 | in terms of human disease is the B virus, liver, liver, |
|
| 59:22 | disease. OK. Um OK. the OK, just recapping. So |
|
| 59:30 | the structure virus, remembering this. . Uh capture type genome type, |
|
| 59:37 | your envelope spikes, et cetera. And then uh we'll, we'll get |
|
| 59:45 | uh eco ecology and uh large viruses isn't that much. But I'm afraid |
|
| 59:52 | wait until the end, it'll be applicable there. So, uh so |
|
| 59:57 | went through the basics of a life previously. Uh So we're gonna, |
|
| 60:04 | this is just really just reiterating what talked about before. So remember it's |
|
| 60:09 | about host recognition that's, that begins cycle. Um Remember how this relates |
|
| 60:15 | host range and tissue specificity of recognizing host cell um entry. So the |
|
| 60:23 | structure may come into the cell and typical for animal viruses. Uh bacterial |
|
| 60:28 | know only the genome comes in uh , it's, you know, copy |
|
| 60:34 | genome, it could be integrating into genome, that's what they do. |
|
| 60:38 | If not, whatever the case, it's gonna replicate, it's gonna go |
|
| 60:42 | all these steps here. OK. we'll see different variations depending on the |
|
| 60:47 | type. OK. So let's uh with bacterial viruses the more simpler. |
|
| 60:54 | We'll start with this question here. . So we're looking at uh so |
|
| 61:01 | , remember, page is refers to viruses. OK. So we're looking |
|
| 61:07 | um uh which is not a part Atlantic Sage cycle. Hm. So |
|
| 61:15 | the operative term there. No. . OK. So the, the |
|
| 62:10 | that are um the F is So the, the two that are |
|
| 62:13 | here are which ones? Yeah. D and E if I heard |
|
| 62:22 | So um these are virulent page, temperate and uh that's false. Only |
|
| 62:34 | genome enters the cell. OK. we look at two types here. |
|
| 62:39 | so the same um with animal the same thing applies. So there's |
|
| 62:44 | animal viruses, lytic bacterial viruses. And so basically a light sage or |
|
| 62:52 | LAIC virus, their mode of operation recognize host infect host, make viruses |
|
| 63:01 | host. That's basically it. And um of course, like with |
|
| 63:07 | viral infection, we have recognition So very typical structure for bacterial virus |
|
| 63:15 | terminus that tailed virus, your book it. So a and that, |
|
| 63:20 | I mentioned that tube in the middle and so the genome enters everything else |
|
| 63:26 | outside. OK. Um Your lysogenic . So there's an equivalent in animal |
|
| 63:33 | , we call them um uh we call them lysogenic, we call them |
|
| 63:38 | viruses. OK? They form a state here. They call them |
|
| 63:45 | OK. And so uh actual integration the viral genome into the host |
|
| 63:51 | OK. So we call them temperate they can, you know, not |
|
| 63:57 | anything to the cell, leave the alone and they then they can kill |
|
| 64:00 | cell. OK. So a like page has a part portion of their |
|
| 64:07 | where they're just integrated into the host doing nothing, right? And the |
|
| 64:11 | cell is perfectly fine, just keeps no problems. But uh eventually it |
|
| 64:17 | gonna replicate, it will have to into the light cycle and to make |
|
| 64:22 | viruses. So it kind of goes both, both uh sides. And |
|
| 64:27 | it all depends on what is the of the host cell pretty much. |
|
| 64:34 | . And that determines which way it . OK. So with the lighting |
|
| 64:39 | , OK? Um It involves, me just go real, I'm gonna |
|
| 64:44 | you. So it involves all of . OK. That's a light |
|
| 64:50 | OK. So uh enter the And so again, only the genome |
|
| 64:56 | a page is entering OK. Then has uh produces viral enzymes to degrade |
|
| 65:05 | host chromosome, which is right degrades. It uses those nucleotides for |
|
| 65:10 | own use. Um transcribes, translates protein, assembles, um inserts the |
|
| 65:18 | into the caps and heads and then . And so at 200 to 500 |
|
| 65:24 | , that's a lot of phage coming of a one host cell. |
|
| 65:30 | And typically, that's enough just to and kill the cell. They also |
|
| 65:34 | things like lysozyme that breaks apart the wall and uh basically just destroys the |
|
| 65:41 | . Um you can, and this acts very fast. So you can |
|
| 65:46 | if you have 200 to 500 of coming out, they'll quickly infect more |
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| 65:51 | . And so it actually becomes like exponential, you know, exponential |
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| 65:57 | Um And so, so that's a phase. Now, the lysogenic type |
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| 66:04 | that, but it also has this . OK. But again, just |
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| 66:10 | reiterate the lytic virus will not have as part of its thing, it |
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| 66:18 | has just this lighting cycle. So misogyny um going this route means |
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| 66:26 | integrates is the prophage uh in the . And so this is not detrimental |
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| 66:34 | the host cell at all. Um it's no burden. So the host |
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| 66:39 | can continue to replicate and this normal . OK. But even though the |
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| 66:46 | isn't technically replicating forming new pages, is replicating its genome right as the |
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| 66:54 | divides. So, of course, prophage is along for the ride, |
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| 67:00 | . So each of these generations of , each containing that prophage, |
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| 67:07 | So, you know how fast bacteria grow. So um you know, |
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| 67:12 | several 100,000 cells can form and each them carrying a part of that carrying |
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| 67:17 | prophage. OK. So then it an issue of OK. When do |
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| 67:22 | go to the lighting cycle? Because that's ultimately how it's going to |
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| 67:28 | more fate. OK. And so different cues for that. Uh very |
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| 67:34 | it's um the, the health of cell. OK. So if you |
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| 67:41 | to think in terms of, if it goes to the light |
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| 67:45 | we're going to produce page particles and perpetuate, right? The species, |
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| 67:53 | ? We want to be able to more cells, right? So you'd |
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| 67:58 | there to be a enough host cells to be infected, right? |
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| 68:05 | if you have, so the cells pretty healthy and they're growing like |
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| 68:11 | Ok, then that's probably a good to say, ok, let's let's |
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| 68:19 | cycle because we can be assured that gonna be lots of hotels around. |
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| 68:26 | . And so, uh that's makes , right? So you have lots |
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| 68:30 | susceptible hosts in the population that's growing quickly. You know, from the |
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| 68:35 | of the age, that's probably a time to, to get into the |
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| 68:39 | cycle and do that. Ok. not a good idea to do that |
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| 68:43 | the cells are kind of starving, maybe limping along growing slowly because of |
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| 68:49 | kind of a stress or something because there's probably not a lot of the |
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| 68:54 | growth rate, there's probably not a of host cells in the population |
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| 68:58 | right? So if they go through cycle, then these may not have |
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| 69:03 | host to find and replicate. So that's kind of how the nutrient |
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| 69:10 | or, or the state of the cell can kind of influence, influence |
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| 69:14 | uh which way it goes. And you know, we didn't go |
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| 69:18 | it. But, you know, prophet itself is, has some virus |
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| 69:25 | proteins being made that kind of sense going on in the cell, there's |
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| 69:29 | molecules in, in a host cell that, that, that can determine |
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| 69:34 | kind of the energy state of the . OK. And, and the |
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| 69:38 | has, has proteins that can kind sense, sense that. OK. |
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| 69:42 | so it's kind of how it bases to stay or go into lighting |
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| 69:47 | That's a fine line, right? even if the cells are stressed, |
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| 69:53 | not growing well. And the page , OK, let's not exit |
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| 69:57 | It could be that the whole cells so bad, but now they begin |
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| 70:01 | die. And so of course, know, you'll want to want to |
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| 70:06 | out of there because you're gonna go with the ship otherwise. So |
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| 70:10 | it can be a fine line in of, uh, it's its own |
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| 70:15 | preservation and when to kind of jump , so to speak. Ok. |
|
| 70:22 | , that makes sense. Yeah, think it makes sense. Um |
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| 70:29 | please stop. That's probably a good . Um, any questions? All |
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| 70:35 | . So, um, we'll see in a couple, uh, |
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| 70:39 | after next week. So you got few days, uh, 10 days |
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| 70:42 | so. So, um, have fun next week. We'll see you |
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| 70:52 | . |
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