| 00:01 | But uh, let's see here. . Ok, folks. Um thanks |
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| 00:17 | coming. Yeah, 123 look like people there. Yeah, maybe close |
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| 00:25 | 100 I guess 35 100. That's bad. So, um, that's |
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| 00:33 | and 3rd, 3rd of you, like that. Anyway, thanks for |
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| 00:40 | . Um I'd rather have class and this way than being in my office |
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| 00:45 | myself, recording, you know, posting it. So anyway, |
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| 00:51 | the, uh, let me turn down a little bit. Ok. |
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| 00:56 | Let's see. Let's see. um, we're gonna continue on with |
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| 01:02 | six. Of course. Uh We , we won't, we'll leave some |
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| 01:08 | left on Tuesday. Uh I think we won't be here the whole |
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| 01:13 | maybe an hour, I'm guessing. Of course you have questions, |
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| 01:18 | uh, let me know and, , so we leave a little bit |
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| 01:22 | , for next Tuesday and so Tuesday be probably be, will be a |
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| 01:26 | class. Ok. And, anyway, so we start on unit |
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| 01:32 | , uh, next Thursday. So , I haven't posted stuff yet. |
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| 01:36 | , I'll do that today and tomorrow my goal there to get that all |
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| 01:41 | um for the next unit. uh what else? Um so smart |
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| 01:48 | assignment due Monday and uh unit unit . So remember that's gonna be a |
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| 01:53 | lengthier, more comprehensive. So, so and and a little bit longer |
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| 01:59 | have longer to do these obviously. um just be aware of that and |
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| 02:04 | I think that's it uh for that of stuff. So let's look at |
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| 02:09 | uh like we always do kind of recap of what we've been doing. |
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| 02:16 | . So we started this unit uh viruses Tuesday and went through kind of |
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| 02:23 | structure. So it's a kind of bit of a road map of the |
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| 02:29 | virals virus structure to remember all virus at their most basic uh level, |
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| 02:37 | a protein coat captured in a So they, they all have that |
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| 02:41 | of course, I mean, they're have viral proteins obviously as well. |
|
| 02:45 | , um so, but we you know, it can be different |
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| 02:49 | shapes, right, asymmetric symmetric uh icosahedron, those geometric shapes. |
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| 02:57 | And then beyond that, uh some of the viral protein structures like |
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| 03:02 | and other things typically for certainly for of a host cell, uh gaining |
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| 03:09 | into the host cell, these kind things. Um And so the |
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| 03:13 | of course, so acquiring an making it a envelope virus obviously, |
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| 03:18 | naked virus is lacking the envelope. . Um So those are most of |
|
| 03:23 | , in terms of classification. We at that, basically, the classification |
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| 03:28 | used that Baltimore system is based on type and the route it takes to |
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| 03:35 | to the MRN A. Right. so we'll go into life cycles, |
|
| 03:39 | went into a little bit of it last time, kind of just in |
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| 03:43 | generic way, so to speak. These are all, these are all |
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| 03:51 | down here at the lower uh So kind of a basic viral replication |
|
| 03:58 | . Obviously, it all starts or . If the virus, you |
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| 04:01 | recognizing the hose can get inside and takes it over and makes it a |
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| 04:05 | to make uh viruses. Um genome enters and uh uh copy |
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| 04:12 | So always remember the end game. I always think in terms of uh |
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| 04:18 | is what's coming in, this is going out, right? And you |
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| 04:24 | to, in order to make you've got, of course, requires |
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| 04:29 | of protein, right? Putting together proteins, putting them together and then |
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| 04:34 | genomes of stuff into each of right? So, um and |
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| 04:38 | of course, we're gonna see today different variations uh along the way, |
|
| 04:44 | in terms of uh how they enter viral types have um uh have different |
|
| 04:50 | that kind of do their things in cells, particularly animal viruses. |
|
| 04:54 | So there's gonna be some variations we'll mention. And so what we |
|
| 04:59 | was with uh our first example of was with a a bacterial virus. |
|
| 05:04 | phage bacteria, p bacterial virus, meaning the same thing. OK. |
|
| 05:11 | uh so virulent and temperate pha so virulent, their mode is basically just |
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| 05:16 | do the light. That's all they , right? So virulent sage |
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| 05:21 | just does this. OK. And and they're, and they um basically |
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| 05:30 | over the the host cell and once enter, they chop up the host |
|
| 05:35 | , they um they can then recycle right. Reuse those nucleotides for their |
|
| 05:41 | replication and then uh quickly assemble into particles and um burst out of the |
|
| 05:48 | . They can have lice lysozyme is enzyme that breaks down the cell wall |
|
| 05:53 | plus combined with simply just the sheer of them in the cell, they |
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| 05:58 | out. OK? And you 500 per cell, that's a |
|
| 06:03 | OK. And you consider, then can go on and infect other host |
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| 06:07 | in the, in the area. . So very this and this can |
|
| 06:10 | very quickly. I mentioned last the uh these are the t even |
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| 06:14 | as we call them T two T , et cetera. And uh uh |
|
| 06:18 | culture of a one mil culture of E coli can be obliterated in like |
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| 06:24 | or 40 minutes. You get a of P and very quickly goes through |
|
| 06:28 | . In fact, now the lysogenic that's lambda, right? So |
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| 06:32 | they can go through uh a lysogenic will have as part of the |
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| 06:38 | The light cycle because the light cycle what enables it to make new pha |
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| 06:44 | . The lyo part of the cycle where it forms a prophage inserts itself |
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| 06:50 | the chromosome. And um and then it along for the right like the |
|
| 06:55 | , the cell is literally completely Ok. It, it just does |
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| 07:01 | normal growth. It does OK? so if there's food around, it |
|
| 07:06 | like crazy. If it's not so , it doesn't grow as well. |
|
| 07:08 | just the normal, no, um I remember the batch growth, |
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| 07:13 | The lag log, et cetera. just going through this normal growth face |
|
| 07:17 | the genome is along for the ride . OK? OK. And |
|
| 07:22 | um but obviously, you can see uh under good conditions, bacteria can |
|
| 07:28 | very fast. So all these generations are forming each contain a copy of |
|
| 07:33 | prophage. And so when the pha it's time to get out, |
|
| 07:38 | It's gonna go through the light OK? And now you're talking |
|
| 07:43 | you know, lots of bacterial cells , and it doesn't all happen at |
|
| 07:47 | , right? But it does happen that eventually these can all go through |
|
| 07:53 | cycle and you're gonna have lots of at the end. OK? |
|
| 07:56 | the control, this is all um p we don't go into this, |
|
| 08:01 | the, the phage prophage itself is synthesizing synthesizing regulatory proteins to kind |
|
| 08:08 | monitor the the host cell condition if will. Ok. And so |
|
| 08:16 | it's, it's um a function of the state of the health of the |
|
| 08:23 | cell? Is it being bombarded with or high temperature or IP H or |
|
| 08:29 | ? Uh that's gonna stress the cell then of course, if they doesn't |
|
| 08:32 | to die with the cell, it then enter like cycle, make new |
|
| 08:38 | , um nutrients can have an uh less nutrients, of course, |
|
| 08:42 | as healthy. Um But also you to consider um you know, the |
|
| 08:50 | of, of, of phage that infected into the cells. How, |
|
| 08:55 | let me say it a different how many host cells are infected? |
|
| 09:00 | . Because it could be that if there's um lots of cells, |
|
| 09:04 | cells are very healthy and are Ok? That if the phage gives |
|
| 09:09 | signal, OK, let's initiate lighting . OK. Then there may not |
|
| 09:15 | uh any host cells to, to , right? Because if they all |
|
| 09:20 | of turn on relative, but at same time, then they produce phage |
|
| 09:24 | and they come out, but then host cells are all dead, there's |
|
| 09:28 | to effect, right? So it to kind of, they have to |
|
| 09:30 | of gauge both, you know, host cells themselves and their, and |
|
| 09:36 | uh state of health. And then p that have affected other host cells |
|
| 09:43 | , I read that this is relatively . Is uh there, there |
|
| 09:46 | there are ways of prophage can tell levels of host cell infectivity if you |
|
| 09:53 | , right. So, pro presumably protein signals of some sort. |
|
| 09:57 | So kind of both of those things a factor, right? Because if |
|
| 10:00 | , if you come out right right, burst out of the |
|
| 10:04 | You know, the assumption is you host cells that you can affect, |
|
| 10:08 | ? And if you don't, then in trouble if you're the virus |
|
| 10:13 | So um does that logic makes Yeah. So, uh again, |
|
| 10:20 | one thing to make viral particles, what they wanna do. But the |
|
| 10:22 | thing is make sure there's hosts around you come out. OK. So |
|
| 10:26 | of those uh uh play a OK. So, um so the |
|
| 10:33 | , the last one, so we've light P lysogenic pha, then we |
|
| 10:39 | this third group. OK. The group is kind of a kind of |
|
| 10:44 | , it's a, a not lysogenic ? Because it's not integrating into the |
|
| 10:52 | . OK. But it, but stays in the cell. OK? |
|
| 10:57 | the host cell remains alive. So it's not tic, but it's |
|
| 11:01 | lysogenic, it's kind of in OK. And so the um uh |
|
| 11:08 | M 13 is actually what we call filamentous stage. It's like a uh |
|
| 11:14 | , so to speak. Uh it um comes inside the cell but it |
|
| 11:21 | not, does not integrate, So it's not forming a oxygen. |
|
| 11:26 | . Um But what it does, will synthesize, you know, go |
|
| 11:31 | , go through it cycle, synthesize proteins. OK? Copy it, |
|
| 11:35 | assemble, right? And then the 13 page comes out. OK. |
|
| 11:41 | , this process does not kill the I mean kill the host cell, |
|
| 11:46 | does not kill the host cell. . So what is the effect of |
|
| 11:51 | host cell? Well, um it because the virus is in there using |
|
| 11:58 | resources uh in, in, in in carrying out protein expression in copying |
|
| 12:06 | genome, right? It does take E that has an effect on the |
|
| 12:10 | , right? Obviously, it would much happier and growing much faster if |
|
| 12:14 | didn't have that to deal with, ? But it does. And so |
|
| 12:18 | effect comes and now it has the cells don't grow so fast. |
|
| 12:23 | They're still alive, right? But , they're kind of just kind of |
|
| 12:26 | the slower growth mode now. Um what happens is uh then, you |
|
| 12:33 | , m 13 continues to replicate and out at a low rate. And |
|
| 12:38 | the other thing is it has to out at, it can't come out |
|
| 12:43 | this rate. Let me just back for a second at this, this |
|
| 12:49 | where you have 200 to 500 the can't survive that. It's too much |
|
| 12:53 | it comes out, I can't give a number. Exactly. But it's |
|
| 12:57 | in the single to low, double per cell. OK? And |
|
| 13:04 | so it's a little bit different strategy what stage has. OK. So |
|
| 13:11 | one thing, M 13 benefits from this kind of life cycle is what's |
|
| 13:18 | , what's the main advantage of doing , of having this kind of |
|
| 13:24 | But I guess so you see M , these arrows of course, represent |
|
| 13:29 | divisions, the host cell dividing. . So M 13, always, |
|
| 13:36 | it comes out, when a when a new viruses come out because |
|
| 13:39 | not killing the host, it always what available to it because this guy |
|
| 13:47 | want to do what people will want infect a host cell. So because |
|
| 13:53 | done doing it this way and the rate doesn't kill the host. It |
|
| 13:58 | has, is insured of always having host around. OK? Whereas there |
|
| 14:03 | a danger if you're this type, light page here that these guys |
|
| 14:10 | can go through these cells so fast you may not, they may not |
|
| 14:13 | a host to infect. OK. the um the uh M 13 |
|
| 14:21 | uh they have to, they have multiply slow as a result, but |
|
| 14:26 | do have hotels always around for So that's kind of the, the |
|
| 14:31 | the, what they see as the and it is a benefit. |
|
| 14:36 | Um Right, they always have a . OK. So they always have |
|
| 14:41 | host around. OK. So remember this is not Lioy. So |
|
| 14:46 | M 13 DNA is not going into chromosome, it's staying outside and doing |
|
| 14:53 | replication thing. We're just doing it , at a low, low |
|
| 14:58 | low enough. So it doesn't kill host cell. Ok. Um Any |
|
| 15:03 | about that? OK. So we lex leage lysogenic P stage and M |
|
| 15:10 | , right? So make sure you kind of differentiate between these three. |
|
| 15:16 | . Um OK. So both with viruses and we talk about animal |
|
| 15:24 | Next host cells of course, have to prevent um or at least uh |
|
| 15:34 | viral infection, right? So they host defenses. OK. So genetic |
|
| 15:38 | is a feature of any, any thing that's infected by a virus. |
|
| 15:43 | has the ability for this, for to occur where you simply have a |
|
| 15:47 | that results. So remember the virus into the host is through uh proteins |
|
| 15:54 | the surface. So you have to and that enables entry. OK. |
|
| 15:58 | so if you have a mutation that the protein sequence of those receptors, |
|
| 16:06 | you will, then that can, know, that's like changing the lock |
|
| 16:10 | now that he and lock don't fit virus can't get in, right? |
|
| 16:14 | maybe they just, they can't get as well. OK. So it |
|
| 16:18 | , there can be degrees of it's not necessarily all or nothing. |
|
| 16:21 | maybe it can't get in as at or maybe just not as efficiently. |
|
| 16:27 | . Uh And either way the host is benefiting from that. OK. |
|
| 16:31 | Restricts end the. So you're probably about these in the context of um |
|
| 16:38 | in DNA technology and gene cloning and putting genes into vectors and so forth |
|
| 16:44 | so restriction enzymes um enable you to that because they recognize specific sequences in |
|
| 16:51 | and then cut, cut it. . So uh heavily used, one |
|
| 16:56 | those types of enzymes is what's called R one. You don't need to |
|
| 17:01 | the sequence. OK. Um This a type of restriction in the nucleus |
|
| 17:04 | it cuts for you to see the or the slashes here between DNA and |
|
| 17:10 | . OK. So again, these these, uh we call this a |
|
| 17:13 | inverted to repeat sequence. So you it's G A att C and then |
|
| 17:18 | other side is G att C. the same thing backwards. So uh |
|
| 17:22 | what they recognize and they'll cut and make these stagger cuts, right? |
|
| 17:27 | so, um so in terms of host defense angle on this, the |
|
| 17:35 | the bacterial restriction in the nuclear will the viral DNA. OK. And |
|
| 17:41 | host, of course, any DNA susceptible to this. So if you're |
|
| 17:45 | host, using this as your way protect yourself, then your DNA better |
|
| 17:49 | somehow shielded from the effect of the . And so it does that by |
|
| 17:55 | methyl groups to its cytosine. And you do that, um, the |
|
| 18:01 | can't bind to it. Ok. you basically put the, these on |
|
| 18:08 | cytosine, right? And in that it doesn't recognize cab won't cut your |
|
| 18:14 | . But of course, the virus have that. And so they're |
|
| 18:17 | Ok. Um, ok. So last mechanism here is one you likely |
|
| 18:24 | heard about in the context of um in genetics course. And you've taken |
|
| 18:29 | um and it's, it's use in in treating genetic diseases. And |
|
| 18:39 | a genetic disease is due to mutations chromosome sequences that produce a defective protein |
|
| 18:47 | leads to whatever the disease state is with that gene. And so this |
|
| 18:55 | one to uh edit that sequence, it and put the proper sequences that |
|
| 19:03 | be there, um active area of going on. And so, um |
|
| 19:09 | they found that technology in bacteria. . So, um so my first |
|
| 19:18 | this, this wasn't even around when first started teaching. So this was |
|
| 19:21 | 10 years, 10 years give or um since we learned about this. |
|
| 19:28 | so uh what it stands for, think of it as a bacterial immune |
|
| 19:33 | . OK. So we'll learn about in um unit four. We get |
|
| 19:39 | immune systems and infectious disease and blah, blah. So um what |
|
| 19:44 | immune system has is, well, one part of the immune system has |
|
| 19:49 | memory. OK? Your uh adaptive system, the one that produces antibodies |
|
| 19:56 | they recognize uh an antigen produce You remember that, right? Your |
|
| 20:01 | can remember that. And so this is the same idea here. |
|
| 20:05 | ? Now we're not forming antibodies or . OK? It's kind of a |
|
| 20:08 | bit more cruder version of that. . And so what happens is during |
|
| 20:14 | , a viral infection, OK. , a segment of the DNA is |
|
| 20:22 | . So what I'm gonna do is gonna go to the next slide |
|
| 20:25 | It's kind of blown up and you see it, see better what's going |
|
| 20:28 | . OK. So let's look at here. OK. So here comes |
|
| 20:32 | viral infection. Now, the, , the entity that does this is |
|
| 20:39 | called a CAS protein that's for cascade it will bind to the DNA and |
|
| 20:49 | has enzymatic activity as well. So will cleave out a portion of |
|
| 20:54 | OK? They call it a OK? And so this ends up |
|
| 21:01 | the host DNA. OK. so this little, this little t |
|
| 21:06 | represents uh a sequence of nucleotides, ? I think in the range of |
|
| 21:15 | to 50 I believe. And so so that segment then is inserted into |
|
| 21:21 | host and there's a region where it all these. OK. So, |
|
| 21:25 | know, the cell itself depending on many times it's been infected previously, |
|
| 21:29 | by various viruses. Uh If it that each time, then it will |
|
| 21:36 | a collection of these previous viral sequences the in its DNA in this |
|
| 21:43 | OK. So that, that basically what is forming the um the memory |
|
| 21:52 | here, right? So it's a of knowing what infected previously is is |
|
| 21:57 | in here. OK. Think of as like a li library, there's |
|
| 22:01 | library and each spacer is a right? So this is this |
|
| 22:06 | this one book is a virus From this time, the next book |
|
| 22:11 | a different viral infection and so OK. So you're kind of just |
|
| 22:15 | in this library if you will. . So um OK. So then |
|
| 22:24 | the course of a viral infection that , it will transcribe that region OK |
|
| 22:30 | RN A and then process it into segments. OK? That they call |
|
| 22:38 | RNAs. OK. So the, premise here is that uh one of |
|
| 22:45 | will be homologous to the incoming viral that's infecting it. OK. And |
|
| 22:52 | again, here comes the cast again, is involved involved in |
|
| 22:56 | It was a combination of the complex this cascade protein and the CRISPR RN |
|
| 23:04 | . OK. So again, it's OK. Which one of these, |
|
| 23:08 | it is, is homologous to the infection that's occurring. OK. |
|
| 23:14 | so the end result is to bind that segment and then uh inactivate it |
|
| 23:23 | . It cleave it basically destroying OK. And oops. And so |
|
| 23:30 | , it's, it's the collection of in the CRISPR region that's kind of |
|
| 23:34 | air quotes memory aspect. OK. it can, it can, um |
|
| 23:40 | it does the CRISPR rnas, then of those maybe is something that |
|
| 23:44 | it's seen before. OK. Um of, think of the CRISPR RN |
|
| 23:48 | as like the quasi antibody if you . OK. Um But it has |
|
| 23:54 | kind of similar function. OK. can recognize previous, the previous host |
|
| 24:00 | previous viral infection. OK. Um there any questions about that? |
|
| 24:07 | So, you know, in terms how this works for, you |
|
| 24:12 | genetic diseases, you know, we , we can engineer particular um CRISPR |
|
| 24:19 | that can recognize these defective sequences and is basically an editing function with a |
|
| 24:26 | protein to kind of chop it out then, and then replace it with |
|
| 24:30 | right sequence. So it's um it's and effective in some cases, but |
|
| 24:34 | really still in development. OK. OK. So that, that's the |
|
| 24:41 | virus part of this life cycle. . So now from here on now |
|
| 24:46 | all animal viruses. OK. So look at this question. Let's remember |
|
| 24:51 | questions today are for, for We'll go ahead and uh respond and |
|
| 24:56 | what we get here. OK. the type of life cycle an animal |
|
| 25:03 | possesses, it's mostly determined by So animal virus infects uh gets entry |
|
| 25:12 | the cell then kind of what happens that is determined by this? |
|
| 25:45 | No. Ok. It came down 10, 543. Mhm. |
|
| 26:00 | So, yeah, it's certainly a type. Ok. So, um |
|
| 26:09 | DNA versus RN A virus, uh gonna go typically go different destinations. |
|
| 26:17 | . And we'll see why that Ok. So, so back to |
|
| 26:22 | so the animal viruses remember the this concept of tropism, right? So |
|
| 26:28 | , that's think of it as tissue . OK. So, in a |
|
| 26:33 | host, what how many different cell can infect? Right. So, |
|
| 26:37 | a cold virus uh shown here, , we have um it binds to |
|
| 26:43 | epithelial cells and the mucous membranes, nose throat, um recognizing this particular |
|
| 26:51 | glycoprotein uh called icam. OK. are found on, on your |
|
| 26:57 | uh they help with attachment to surfaces things. So um uh that's what |
|
| 27:02 | recognize and get entry in. So um and so of course, this |
|
| 27:07 | be broader and narrow. We mentioned before, right? Ebola is rather |
|
| 27:11 | . It can affect different cell types the body. As a general |
|
| 27:14 | most viruses are are fairly narrow. . Infecting either respiratory cells, um |
|
| 27:23 | membrane of nose throat, these kind things, um STD S infect uh |
|
| 27:30 | of the reproductive structures. So most have kind of, you know, |
|
| 27:34 | so broad tropism. OK. um so again, we said it |
|
| 27:40 | on the genome in terms of replication . OK. So DNA viruses um |
|
| 27:46 | course, rely on the host replication , right? And so is a |
|
| 27:54 | virus. So again, we're talking viruses, OK. Where is it |
|
| 27:59 | likely to going in itself Exor Where? Right? In the |
|
| 28:07 | Because and so think about a animal , like one of your cells that |
|
| 28:17 | mitosis, for example, OK. you're so remember the, remember the |
|
| 28:23 | cell cycle, right? So you're mitosis um and you're in s |
|
| 28:30 | what's happening in that phase? Right. DNA is being chromosomes are |
|
| 28:36 | replicated, right? And so of , that's happening in the one in |
|
| 28:41 | nucleus, right? And so what's the nucleus that the DNA virus needs |
|
| 28:47 | DNA plume, right? So that's they typically go there is to access |
|
| 28:53 | DNA ply. That's being, that's , that's where it's used in |
|
| 28:58 | in a animal cell in the Um Now with all these, you |
|
| 29:04 | , this is not always a a hard and fast rule. OK? |
|
| 29:12 | um there are gonna be variations, DNA viruses have their own host DNA |
|
| 29:17 | , but many don't. OK. there's, there's gonna be variations for |
|
| 29:22 | of these things we talk about. . So, or viruses, remember |
|
| 29:26 | got that RN A dependent RN A , right? So your type of |
|
| 29:31 | A plym and what eukaryotic cells have what we call DNA dependent, not |
|
| 29:39 | A, right? Because we don't RN A molecules, we copy DNNRN |
|
| 29:44 | , we don't copy RN A in RN A. OK. And so |
|
| 29:48 | virus virus must have that enzyme to, to copy their genome transcribe |
|
| 29:55 | RN A. OK. Um Retroviruses , are an RN A virus, |
|
| 30:02 | they're in a kind of a separate . OK? Because they go through |
|
| 30:07 | DNA intermediate, right? Um And reverse transcript base enables that. |
|
| 30:14 | So, all right. So step for any virus is gonna be |
|
| 30:22 | OK? And so animal viruses have ways to do this. There are |
|
| 30:28 | of them exploit uh existing entry processes that um molecules use to get into |
|
| 30:38 | cells. They kind of use, those mechanisms. Um And this process |
|
| 30:43 | un coding that is to release the from the capsule, OK, into |
|
| 30:49 | , into the cytoplasm. And so , OK? Is uh where you'll |
|
| 30:59 | . Here's an envelope virus and it fuse again, this is all molecule |
|
| 31:05 | and the fusion, the membrane fuses the host cell membrane. OK? |
|
| 31:10 | as a result, here's the capsid then uh these can be digested to |
|
| 31:16 | the genome. OK. Now, uh this is actually an RN A |
|
| 31:21 | here. Uh and so RN A do their thing, replication cycle outside |
|
| 31:29 | nucleus. They don't need to go the nucleus. They don't need DNA |
|
| 31:32 | . OK. So during do do life cycle outside the nucleus. |
|
| 31:38 | Um a endo zone. So encoding an endo zone. OK. So |
|
| 31:45 | example of this is like a cholesterol take in cholesterol into your cells by |
|
| 31:50 | same mechanism, it's called receptor mediated . So again, uh recognition of |
|
| 31:57 | molecules on the surface that induces the of a endos basically a vesicle is |
|
| 32:03 | wrap around it. OK? And these typically fuse with like a |
|
| 32:07 | So remember lysosomes are digestive organelles and will serve to kind of break down |
|
| 32:13 | caps and then release the um uh the RN A genome. OK. |
|
| 32:18 | this, in this example, RN genome, um you can have uh |
|
| 32:24 | coding occurring at the nucleus if it's DNA virus. OK. The same |
|
| 32:30 | uh binding to the host inducing endos , fiscal travels to the nucleus and |
|
| 32:36 | where the encoding is is finalized. . Again, being a DNA |
|
| 32:42 | that's where it wants to go. . So um OK. The um |
|
| 32:51 | there there are variations. So because virus is one of those, the |
|
| 32:55 | virus is an RN A virus. actually does go into the nucleus for |
|
| 33:00 | of its functions. OK. Not grab a DNA plym, but just |
|
| 33:05 | kind of where it just does some its functions. So you know, |
|
| 33:08 | , you do have some outliers like that don't obey the rules if you |
|
| 33:13 | uh but for the most part DNA go to the nucleus RN A viruses |
|
| 33:18 | outside, but you can have a types that don't follow the rules. |
|
| 33:24 | . Um Any questions about this? . All right. So uh |
|
| 33:33 | So a couple of things that viruses do. So, of course, |
|
| 33:37 | the encoding process occurs and you can in the genome replication of viral proteins |
|
| 33:43 | together are being synthesized uh then eventually exit. OK. So 11 type |
|
| 33:51 | exit uh is this so we call . OK. This is what you |
|
| 33:57 | envelope viruses do. OK. And uh so you see here, so |
|
| 34:04 | know, viruses can overtake the the of the cell like the endoplasm |
|
| 34:09 | right? Uh the Goldy apparat or kind of for trafficking proteins and making |
|
| 34:14 | going a certain way certain directions, ? And so viruses can use those |
|
| 34:20 | uh proteins meant to be on the are, you know, are are |
|
| 34:26 | out by the goji. OK? those can come off, go to |
|
| 34:31 | surface and fuse. And so now viral proteins are sitting out here. |
|
| 34:37 | ? And so when a virus is and it exits that membrane kind of |
|
| 34:43 | pinches off around it. OK. it's acquired its envelope and it's viral |
|
| 34:49 | . OK? So that's the nature an envelope virus. Now, if |
|
| 34:53 | occurs at a high rate, the cell will be overwhelmed and die |
|
| 34:59 | it can occur at a low OK. And in doing so as |
|
| 35:04 | virus is butt out, the host is still viable, it's alive. |
|
| 35:10 | . And so it can happen as as this is occurring at a low |
|
| 35:14 | and not overwhelming cell. OK. we see that too. Uh HIV |
|
| 35:20 | can, doesn't, can do OK. Um Right. The |
|
| 35:28 | So this in a nutshell summary DNA viruses in the end, |
|
| 35:33 | this is the case, OK? most replicating the genome replication of |
|
| 35:38 | Um So remember, right, they're a eyo cell. OK. So |
|
| 35:44 | have a transcription in the nucleus and have translation outside the nucleus, |
|
| 35:51 | So they have to uh do that well. OK. And so, |
|
| 35:56 | you, but you, you especially with the DNA virus, you're |
|
| 35:59 | have activities going back and forth and and forth, some stuff occurring in |
|
| 36:03 | nucleus, some outside and then things back in and you assemble. So |
|
| 36:07 | can be quite a a process in of trafficking back and forth in and |
|
| 36:13 | the nucleus and so forth. If assemble the viruses. Um uh a |
|
| 36:18 | virus is generally not, it's complex that reason. Everything typically occurs outside |
|
| 36:23 | nucleus in time. But again, I mentioned, there's a few |
|
| 36:27 | Flu virus is one of those where goes into the nucleus too. So |
|
| 36:30 | have kind of stuff occurring on both . Um So let's uh so the |
|
| 36:37 | example here is a DNA virus. . So Papilloma virus is an example |
|
| 36:41 | that double stranded DNA virus. And , um this is a, it's |
|
| 36:49 | one of one of the most common transmitted diseases. Um It forms like |
|
| 36:56 | warts uh on reproductive structures. Um can be cancerous, right? So |
|
| 37:03 | , I think about 10% of um just let me clarify. 10% of |
|
| 37:11 | are caused by viruses. OK. this is one of them. So |
|
| 37:15 | familiar with um uh cervical cancer is of the, is the cause of |
|
| 37:21 | cancer. OK. Uh I assume very non um causes for that as |
|
| 37:27 | . But uh but certainly this, is a, is, is a |
|
| 37:31 | cause and there's a vaccine for them encourage women to get vaccinated. Uh |
|
| 37:36 | , as uh I think when you're puberty uh to get vaccinated for |
|
| 37:41 | it's effective. Um But regardless, the um so this is one tied |
|
| 37:50 | the growth cycle of the host OK. So uh skin cells is |
|
| 37:58 | of, it's uh what it OK. So here's a cross section |
|
| 38:05 | epithelial tissue and going from left to . OK. So this direction basal |
|
| 38:13 | to carno sites that's going from a change in differentiation of the |
|
| 38:20 | OK. So they begin as basal that are really not growing. |
|
| 38:28 | That then differentiate again, that's all chemical signals, right? Hormones that |
|
| 38:34 | them the K start growing, And that's when they develop into reno |
|
| 38:38 | which are the fully developed uh skin . OK. And so the replication |
|
| 38:47 | the virus is, is tied to . Ok. So, um so |
|
| 38:54 | the basal cells, right, that's the cancerous forms are more likely to |
|
| 39:00 | if they occur is in this stage the cells aren't actively growing. |
|
| 39:05 | And they can insert their um genome the host chromosome. OK. And |
|
| 39:13 | in doing so, they insert themselves a position that creates a mutant |
|
| 39:18 | right? We all know, I'm that, that the one thing that |
|
| 39:23 | cancer cells is uncontrolled. What right. So, um so, |
|
| 39:31 | that's what can happen in some So, but again, it's |
|
| 39:34 | the the cells that are most susceptible those basal cells that aren't really growing |
|
| 39:39 | . OK. Now, uh when do, we're gonna differentiate into these |
|
| 39:45 | growing carno sites, right? Uh when viral to remember. Uh it's |
|
| 39:52 | the availability of DNA pra, And that's gonna only be present if |
|
| 39:58 | host cell itself is replicating, Going through phase mitosis, right? |
|
| 40:04 | that's when the polymerase is available and when H PB will begin to then |
|
| 40:10 | produced. And that's where you see uh viruses being uh produced and, |
|
| 40:16 | exiting. OK. So, tied to the to the growth cycle |
|
| 40:21 | the host cell. OK. Uh this is picture here that shows you |
|
| 40:26 | that right. So here's a a genome is encoded at the |
|
| 40:31 | OK. And then um we have replication of the genome. Of |
|
| 40:37 | we have transcription occurring simultaneously. The have to go out here, I |
|
| 40:43 | where translation occurs outside the nucleus. Then those proteins have to come back |
|
| 40:48 | the nucleus because that's where assembly the occurs and then come out. |
|
| 40:54 | And so um shedding is a term to kind of describe the, the |
|
| 41:01 | of these viruses from the, from host cell. OK. Um |
|
| 41:07 | Any questions about that one? So a DNA virus. OK. Um |
|
| 41:15 | right, let's look at this question . So our RN A dependent. |
|
| 41:18 | we're gonna talk about RN A viruses here in different kinds and put that |
|
| 41:25 | in this. So a think that hold on. OK. So RN |
|
| 41:32 | dependent RN a polymerase enzyme is is not used by what? |
|
| 41:39 | Who doesn't need it? OK. down 54 to one. Yeah, |
|
| 42:29 | gonna be the retrovirus. OK. Because I remember it, it goes |
|
| 42:35 | DNA and OK. And um let's first. Well, let's just kind |
|
| 42:41 | have a little bit of an overview . So remember uh the RN A |
|
| 42:45 | genome, right? Depending on what it is. There's different uses for |
|
| 42:50 | um the genome, right? So template, it can be different templates |
|
| 42:55 | on the type. OK. So the template for translation. So basically |
|
| 43:01 | you see plus RN A, that's of it as messenger RN A, |
|
| 43:05 | ? A ribosome can plop on it begin synthesizing. OK. Um If |
|
| 43:12 | an A minus R A virus, sorry. Come on. Mm |
|
| 43:20 | So bias or virus it um that is not a form that's translatable, |
|
| 43:28 | have the, doesn't have the um parts on it to make it |
|
| 43:33 | OK? And, and one of , we'll learn about this next |
|
| 43:38 | One of those things is a Aris binding site, right? That has |
|
| 43:41 | be present for, for the vibes the bind and the mount minus RN |
|
| 43:45 | virus doesn't have that the minus form have it. So you have to |
|
| 43:49 | this into a plus form. That's Hawaii. This is a template |
|
| 43:53 | MRN A OK. Then uh template DNA synthesis. That's the retrovirus. |
|
| 43:59 | . So that's why this one doesn't , does not need this enzyme |
|
| 44:04 | OK? Um It has the uh transcript. OK. And right |
|
| 44:10 | here we go. So DNA goes RN A to DNA RT as reverse |
|
| 44:15 | because its life cycle is to integrate the host. OK. Uh But |
|
| 44:20 | course, I'm just gonna produce viral that will have to go through |
|
| 44:24 | this route RN A protein, but is all through host host enzymes, |
|
| 44:30 | components. OK. Um All So we'll look first at a plus |
|
| 44:37 | A virus. OK? And you need to memorize these types here. |
|
| 44:41 | just put them up there just to you some of the types that are |
|
| 44:44 | this group, um COVID among And OK. So, and I |
|
| 44:50 | of grew it this way to, to, to just always remember. |
|
| 44:56 | right, here's what we're starting right? The virus is gonna |
|
| 44:58 | right? The plus or a virus . What's the end end result? |
|
| 45:02 | want to make lots of viral right? So what do you need |
|
| 45:05 | to make the cap? Right? need genome copies, right? So |
|
| 45:10 | so how is this gonna happen? , we start uh and so we're |
|
| 45:15 | , of course, obviously, it's un coding process has occurred. We |
|
| 45:19 | the the genome is inside the OK? And so step one is |
|
| 45:25 | this enzyme again, viral enzyme is it with it. OK? And |
|
| 45:31 | that into minus RNAs. OK. again, it would be great, |
|
| 45:38 | ? If that could be copied into plus strand, much more efficient, |
|
| 45:41 | ? But that's that, that's just the laws of nucleic acids, |
|
| 45:46 | Because it's just it's complementary base pairing the strands relative to each other or |
|
| 45:50 | minus. That's whether it's rnarnarn A , DNA DNA, it's the same |
|
| 45:56 | , right? So, so we plus copied into a minus. |
|
| 46:01 | And so of course, the the here is we've made lots of |
|
| 46:06 | right? We have lots of stuff . OK? And that can of |
|
| 46:09 | lead to lots of, of, uh transcripts Mrnas, right? That |
|
| 46:16 | become lots of proteins. OK? so the missing piece now is gotta |
|
| 46:22 | genomes into it, right? So plus RNAs serve two purposes. They're |
|
| 46:27 | template to make uh uh translate to proteins and themselves are the genome for |
|
| 46:35 | species. OK? Package it together we're done. OK. Um And |
|
| 46:41 | an example is shown here is uh gonna be a Rhinovirus, cold |
|
| 46:46 | et cetera. Um So, here the encoding process, the plus genome |
|
| 46:53 | . Uh In some cases, I the virus may have uh a preformed |
|
| 47:03 | a dependent RN A plym, but not. So if it's a |
|
| 47:08 | it, it will um copy the for that, make the RN a |
|
| 47:12 | a plum and then we'll um copy right? Copy the plus into a |
|
| 47:17 | strand, right? Minus strands uh to make copies of the plus |
|
| 47:23 | right. So we'll have um a of viral proteins, of course. |
|
| 47:27 | That's kind of what this would It's not really marked here. So |
|
| 47:32 | would be this arrow going this way be translation, OK? Uh making |
|
| 47:48 | uh translating the into the, into proteins for the virus and then assembling |
|
| 47:53 | and then exit. OK. Giving plus RN A progeny. OK. |
|
| 47:59 | then um all right, let's look the minus. All right, here's |
|
| 48:03 | of this measles, mumps, uh et cetera. So again, |
|
| 48:10 | one of these viruses has infected, the encoding has happened here is the |
|
| 48:15 | . OK? And again, remember is the end, the end game |
|
| 48:19 | , right? Make lots of viral , proteins, of course, and |
|
| 48:24 | of genome. OK. So the uh same enzyme we're gonna copy that |
|
| 48:32 | plus RN A. So now we've our, we've got our templates to |
|
| 48:35 | protein. OK. Which we But then remember, we have |
|
| 48:41 | those proteins will assemble into a but they're going to be empty caps |
|
| 48:47 | we have a minus RN A to into it, right? Because that's |
|
| 48:51 | kind of virus that's infecting. So these then plus ras are copied into |
|
| 48:58 | RNAs. OK? And that serves the genome that's inserted. All |
|
| 49:04 | So now we're, we're done. . So um OK. So minus |
|
| 49:13 | plus. Are there any questions about ? I know that the part to |
|
| 49:17 | your head around is the why? plus the plus and blah, |
|
| 49:21 | blah. It's, it's just the that nucleic acids work. OK? |
|
| 49:25 | not, it's not meant to, not a, it's not the fault |
|
| 49:28 | the virus. OK? It's it's just how the, it's a |
|
| 49:32 | between the two, the two types nucleic acid Ok. Have any |
|
| 49:38 | Yeah. For that. Mhm. . Exactly. So it uses it |
|
| 49:48 | , in both, both steps. . That's the only way it can |
|
| 49:53 | its RNAs with that enzyme and when copies it's either gonna be a, |
|
| 49:56 | plus or a minus depending on the . Yeah. Yeah. Yeah. |
|
| 50:11 | . Ok. So back here and one here, you mean what happens |
|
| 50:19 | these? Oh, to these? . So what happens is these are |
|
| 50:25 | just degraded by the cell because um in general don't have a, a |
|
| 50:33 | lifespan. Uh a single of RN to sell. Even if it's the |
|
| 50:39 | own R A. They don't really long typically. And so especially if |
|
| 50:43 | something that's uh likely foreign to the itself, it will just, it'll |
|
| 50:49 | away. Yeah. Yeah. Um know, and, and if |
|
| 50:52 | if these aren't packaged, they will degraded as well. OK. |
|
| 50:58 | uh any other questions? OK. OK. So the last one here |
|
| 51:05 | the one that's different from both of and that's the uh retrovirus. |
|
| 51:11 | Um All right. So it is plus RN A virus. OK. |
|
| 51:17 | it's, its mode is to integrate the chromosome of the host. |
|
| 51:23 | So this is a strictly viral OK. Verse transcript A that's meant |
|
| 51:29 | make a, so again, you , you see the rules here, |
|
| 51:33 | ? It's, it's gonna be a . We're copying a plus and it's |
|
| 51:35 | be a minus strand even though it's , right? Irrelevant, right? |
|
| 51:39 | just you copy mic acids. The made is the opposite of the other |
|
| 51:45 | , right? Plus minus minus Right. So, um so then |
|
| 51:51 | happens is if it's going to integrate the host chromosome, the host chromosome |
|
| 51:57 | double stranded, right? So the inserting into it has to be double |
|
| 52:02 | as well. Right? So what does is it uses host DNA Pras |
|
| 52:08 | make the complimentary copy. Right we have the double strand plus and |
|
| 52:13 | . OK. And that's what can into the host. OK. |
|
| 52:19 | if it's going to, you if it's going to replicate itself, |
|
| 52:22 | , it's gonna have to um produce uh the plus RNAs and make and |
|
| 52:29 | into viral proteins, right? Assemble package and there we go. |
|
| 52:38 | So, um so the life cycle the virus is such that um it |
|
| 52:50 | be in this integrated state in the for years. OK. Before it's |
|
| 52:57 | detectable. OK. So uh the HIV uh causes AIDS uh and other |
|
| 53:07 | . Uh the free leukemia virus, is one that's been used as a |
|
| 53:11 | to study it. Um So it R A virus, right, actually |
|
| 53:17 | two strands. Um anyway, it a type of immune system cell called |
|
| 53:24 | T helper. So we'll talk about at the end. Um T helper |
|
| 53:29 | are the one the one that infects in your body, kind of control |
|
| 53:38 | whole immune response, your death, response. And so, uh if |
|
| 53:44 | end up destroying these, you are getting rid of your adaptive immune response |
|
| 53:52 | the most part. OK. So not a good thing. OK. |
|
| 53:58 | , um so here it comes, it's envelope virus, it will |
|
| 54:04 | uh I think it goes through not really shown here. Uh But |
|
| 54:09 | the encoding releases the, the um genome in a risk transcriptase and we |
|
| 54:17 | that and ran in DNA integrate into host. OK. So again, |
|
| 54:21 | period of being in the host can for a long time. OK. |
|
| 54:27 | It can then at some point Uh And so we call that |
|
| 54:32 | So provirus and prophage. So two because they both represent integrated forms into |
|
| 54:40 | chromosome. But provirus is used for viruses, prophage for bacterial viruses. |
|
| 54:48 | ? Um So a latent state is when it's just kind of sitting in |
|
| 54:52 | cell and the chromosome is kind of doing anything. OK? You don't |
|
| 54:56 | know if you've been infected. But what can have, what can |
|
| 55:01 | in at some point is it stays that, in that integrated state, |
|
| 55:07 | slowly uh transcribes into MRN A that is translated into viral proteins, assembly |
|
| 55:16 | budding. All right. So it out at a rate. OK. |
|
| 55:20 | again, the host cell is still but producing viruses. Ok. And |
|
| 55:26 | not until this gets to a level which, um, is detectable in |
|
| 55:32 | blood. So when the blood test , when you become one becomes HIV |
|
| 55:37 | , then enough of this activity has occurring to, to produce detectable levels |
|
| 55:42 | antigen. Ok. Um, and , of course, as these viruses |
|
| 55:47 | out, they'll infect more of these helper cells. Ok. So at |
|
| 55:53 | point, the levels become detectable and that's when obviously you need to be |
|
| 55:59 | . Ok. Um, and so , a, um, treatment is |
|
| 56:04 | done. Um, there's a drug , uh A ZT. It basically |
|
| 56:10 | with the reverse transcriptase in, in function. But over the years, |
|
| 56:14 | course, the virus has evolved and had to slightly change the chemical nature |
|
| 56:20 | the A ZT to keep up with . Um, to my knowledge, |
|
| 56:23 | like, um, one's, one's treatment, it's like a combination of |
|
| 56:29 | or seven drugs, uh, that given, I believe. And, |
|
| 56:34 | , but it's, you know, from what it was 30 years |
|
| 56:39 | Plus, um, nowadays it's, , it's not curable but it's a |
|
| 56:44 | treatable disease. You can live pretty a normal life, but, |
|
| 56:50 | obviously you have to have access to drug, right? And so, |
|
| 56:54 | , famously anybody know who Magic Johnson professional basketball player, right? |
|
| 57:02 | yeah, back in the eighties, was diagnosed with, uh, hiv |
|
| 57:06 | and he's still very healthy, And kicking. Ok. Uh, |
|
| 57:12 | HIV is endemic epidemic in parts of world, parts of Africa, for |
|
| 57:19 | , people dying of it. why is that? Well, that's |
|
| 57:23 | they don't have access to the And so that's a whole other |
|
| 57:27 | uh, non science discussion. Why going on. But, um, |
|
| 57:32 | , you know, if you have to the medication and, you |
|
| 57:35 | you, it's believe I was, was here when it was the eighties |
|
| 57:40 | mid eighties and the, the AIDS was a full blown pandemic and it |
|
| 57:45 | , it was, uh, it brought to the four, lots of |
|
| 57:51 | issues as you can imagine, Not just medical, you know, |
|
| 57:56 | , epidemic type things, but other cultural stuff as well. So that |
|
| 58:02 | , uh, I mean, and I knew people here at U |
|
| 58:05 | H that had other grad students, couple of them that had, had |
|
| 58:08 | . So it's, it was, was a mess, uh, |
|
| 58:12 | But, uh, like I said , it's, it's certainly come a |
|
| 58:16 | way. So very, very Uh, again, give access to |
|
| 58:20 | medications. Ok. Um Any questions anything today? Let's see. I |
|
| 58:28 | , uh let's look at this and uh we'll call it a day. |
|
| 58:34 | . Let's see here. An RN virus possessing a single plus cent RN |
|
| 58:41 | strand as its genome, right? first have to transcribe this into a |
|
| 58:47 | antisense strand and translate from this minus scent strand into viral proteins, |
|
| 58:53 | Simply true or false. OK. , so if we haven't already signed |
|
| 59:05 | for the exam, remember to go the, the new CASA site, |
|
| 59:08 | ? The CCS S OK. The is uh next Friday, Saturday |
|
| 59:16 | 21st, then, right? um, do download that exam review |
|
| 59:24 | because if it's not on there, not on the test, right? |
|
| 59:30 | right. OK. So the correct is, let me see here. |
|
| 59:43 | we're gonna just basically what the sentence , we're gonna copy that into a |
|
| 59:46 | RN A. So remember that's not , right? The plus is what's |
|
| 59:51 | . OK. Um And so we to go that route, right? |
|
| 59:57 | then translate from there. OK. You could translate. So yeah, |
|
| 60:02 | , that'd be be a question you . It's like, OK, the |
|
| 60:05 | virus and the genome that comes Yeah, you can translate that, |
|
| 60:08 | it's about quantities, right? You to make more. One isn't |
|
| 60:12 | you need to make more because you're make lots of viruses, right? |
|
| 60:16 | So the answer here is false, ? Because minus strand can't be translated |
|
| 60:21 | the plus strand. OK. there's no questions. Enjoy the |
|
| 60:27 | It's |
|
