Video transcript

Considering that I have a cold right now, I can't imagine a more appropriate topic to make a video on than a virus. And I didn't want to make it that thick. A virus, or viruses. And in my opinion, viruses are, on some level, the most fascinating thing in all of biology. Because they really blur the boundary between what is an inanimate object and what is life? I mean if we look at ourselves, or life as one of those things that you know it when you see it. If you see something that, it's born, it grows, it's constantly changing. Maybe it moves around. Maybe it doesn't. But it's metabolizing things around itself. It reproduces and then it dies. You say, hey, that's probably life. And in this, we throw most things that we see-- or we throw in, us. We throw in bacteria. We throw in plants. I mean, I could-- I'm kind of butchering the taxonomy system here, but we tend to know life when we see it. But all viruses are, they're just a bunch of genetic information inside of a protein. Inside of a protein capsule. So let me draw. And the genetic information can come in any form. So it can be an RNA, it could be DNA, it could be single-stranded RNA, double-stranded RNA. Sometimes for single stranded they'll write these two little S's in front of it. Let's say they are talking about double stranded DNA, they'll put a ds in front of it. But the general idea-- and viruses can come in all of these forms-- is that they have some genetic information, some chain of nucleic acids. Either as single or double stranded RNA or single or double stranded DNA. And it's just contained inside some type of protein structure, which is called the capsid. And kind of the classic drawing is kind of an icosahedron type looking thing. Let me see if I can do justice to it. It looks something like this. And not all viruses have to look exactly like this. There's thousands of types of viruses. And we're really just scratching the surface and understanding even what viruses are out there and all of the different ways that they can essentially replicate themselves. We'll talk more about that in the future. And I would suspect that pretty much any possible way of replication probably does somehow exist in the virus world. But they really are just these proteins, these protein capsids, are just made up of a bunch of little proteins put together. And inside they have some genetic material, which might be DNA or it might be RNA. So let me draw their genetic material. The protein is not necessarily transparent, but if it was, you would see some genetic material inside of there. So the question is, is this thing life? It seems pretty inanimate. It doesn't grow. It doesn't change. It doesn't metabolize things. This thing, left to its own devices, is just going to sit there. It's just going to sit there the way a book on a table just sits there. It won't change anything. But what happens is, the debate arises. I mean you might say, hey Sal, when you define it that way, just looks like a bunch of molecules put together. That isn't life. But it starts to seem like life all of a sudden when it comes in contact with the things that we normally consider life. So what viruses do, the classic example is, a virus will attach itself to a cell. So let me draw this thing a little bit smaller. So let's say that this is my virus. I'll draw it as a little hexagon. And what it does is, it'll attach itself to a cell. And it could be any type of cell. It could be a bacteria cell, it could be a plant cell, it could be a human cell. Let me draw the cell here. Cells are usually far larger than the virus. In the case of cells that have soft membranes, the virus figures out some way to enter it. Sometimes it can essentially fuse-- I don't want to complicate the issue-- but sometimes viruses have their own little membranes. And we'll talk about in a second where it gets their membranes. So a virus might have its own membrane like that. That's around its capsid. And then these membranes will fuse. And then the virus will be able to enter into the cell. Now, that's one method. And another method, and they're seldom all the same way. But let's say another method would be, the virus convinces-- just based on some protein receptors on it, or protein receptors on the cells-- and obviously this has to be kind of a Trojan horse type of thing. The cell doesn't want viruses. So the virus has to somehow convince the cell that it's a non-foreign particle. We could do hundreds of videos on how viruses work and it's a continuing field of research. But sometimes you might have a virus that just gets consumed by the cell. Maybe the cell just thinks it's something that it needs to consume. So the cell wraps around it like this. And these sides will eventually merge. And then the cell and the virus will go into it. This is called endocytosis. I'll just talk about that. It just brings it into its cytoplasm. It doesn't happen just to viruses. But this is one mechanism that can enter. And then in cases where the cell in question-- for example in the situation with bacteria-- if the cell has a very hard shell-- let me do it in a good color. So let's say that this is a bacteria right here. And it has a hard shell. The viruses don't even enter the cell. They just hang out outside of the cell like this. Not drawing to scale. And they actually inject their genetic material. So there's obviously a huge-- there's a wide variety of ways of how the viruses get into cells. But that's beside the point. The interesting thing is that they do get into the cell. And once they do get into the cell, they release their genetic material into the cell. So their genetic material will float around. If their genetic material is already in the form of RNA-- and I could imagine almost every possibility of different ways for viruses to work probably do exist in nature. We just haven't found them. But the ones that we've already found really do kind of do it in every possible way. So if they have RNA, this RNA can immediately start being used to essentially-- let's say this is the nucleus of the cell. That's the nucleus of the cell and it normally has the DNA in it like that. Maybe I'll do the DNA in a different color. But DNA gets transcribed into RNA, normally. So normally, the cell, this a normal working cell, the RNA exits the nucleus, it goes to the ribosomes, and then you have the RNA in conjunction with the tRNA and it produces these proteins. The RNA codes for different proteins. And I talk about that in a different video. So these proteins get formed and eventually, they can form the different structures in a cell. But what a virus does is it hijacks this process here. Hijacks this mechanism. This RNA will essentially go and do what the cell's own RNA would have done. And it starts coding for its own proteins. Obviously it's not going to code for the same things there. And actually some of the first proteins it codes for often start killing the DNA and the RNA that might otherwise compete with it. So it codes its own proteins. And then those proteins start making more viral shells. So those proteins just start constructing more and more viral shells. At the same time, this RNA is replicating. It's using the cell's own mechanisms. Left to its own devices it would just sit there. But once it enters into a cell it can use all of the nice machinery that a cell has around to replicate itself. And it's kind of amazing, just the biochemistry of it. That these RNA molecules then find themselves back in these capsids. And then once there's enough of these and the cell has essentially all of its resources have been depleted, the viruses, these individual new viruses that have replicated themselves using all of the cell's mechanisms, will find some way to exit the cell. The most-- I don't want to say, typical, because we haven't even discovered all the different types of viruses there are-- but one that's, I guess, talked about the most, is when there's enough of these, they'll release proteins or they'll construct proteins. Because they don't make their own. That essentially cause the cell to either kill itself or its membrane to dissolve. So the membrane dissolves. And essentially the cell lyses. Let me write that down. The cell lyses. And lyses just means that the cell's membrane just disappears. And then all of these guys can emerge for themselves. Now I talked about before that have some of these guys, that they have their own membrane. So how did they get there, these kind of bilipid membranes? Well some of them, what they do is, once they replicate inside of a cell, they exit maybe not even killing-- they don't have to lyse. Everything I talk about, these are specific ways that a virus might work. But viruses really kind of explore-- well different types of viruses do almost every different combination you could imagine of replicating and coding for proteins and escaping from cells. Some of them just bud. And when they bud, they essentially, you can kind of imagine that they push against the cell wall, or the membrane. I shouldn't say cell wall. The cell's outer membrane. And then when they push against it, they take some of the membrane with them. Until eventually the cell will-- when this goes up enough, this'll pop together and it'll take some of the membrane with it. And you could imagine why that would be useful thing to have with you. Because now that you have this membrane, you kind of look like this cell. So when you want to go infect another cell like this, you're not going to necessarily look like a foreign particle. So it's a very useful way to look like something that you're not. And if you don't think that this is creepy-crawly enough, that you're hijacking the DNA of an organism, viruses can actually change the DNA an organism. And actually one of the most common examples is HIV virus. Let me write that down. HIV, which is a type of retrovirus, which is fascinating. Because what they do is, so they have RNA in them. And when they enter into a cell, let's say that they got into the cell. So it's inside of the cell like this. They actually bring along with them a protein. And every time you say, where do they get this protein? All of this stuff came from a different cell. They use some other cell's amino acids and ribosomes and nucleic acids and everything to build themselves. So any proteins that they have in them came from another cell. But they bring with them, this protein reverse transcriptase. And the reverse transcriptase takes their RNA and codes it into DNA. So its RNA to DNA. Which when it was first discovered was, kind of, people always thought that you always went from DNA to RNA, but this kind of broke that paradigm. But it codes from RNA to DNA. And if that's not bad enough, it'll incorporate that DNA into the DNA of the host cell. So that DNA will incorporate itself into the DNA of the host cell. Let's say the yellow is the DNA of the host cell. And this is its nucleus. So it actually messes with the genetic makeup of what it's infecting. And when I made the videos on bacteria I said, hey for every one human cell we have twenty bacteria cells. And they live with us and they're useful and they're part of us and they're 10% of our dry mass and all of that. But bacteria are kind of along for the ride. They don't change who we are. But these retroviruses, they're actually changing our genetic makeup. I mean, my genes, I take very personally. They define who I am. But these guys will actually go in and change my genetic makeup. And then once they're part of the DNA, then just the natural DNA to RNA to protein process will code their actual proteins. Or their-- what they need to-- so sometimes they'll lay dormant and do nothing. And sometimes-- let's say sometimes in some type of environmental trigger, they'll start coding for themselves again. And they'll start producing more. But they're producing it directly from the organism's cell's DNA. They become part of the organism. I mean I can't imagine a more intimate way to become part of an organism than to become part of its DNA. I can't imagine any other way to actually define an organism. And if this by itself is not eerie enough, and just so you know, this notion right here, when a virus becomes part of an organism's DNA, this is called a provirus. But if this isn't eerie enough, they estimate-- so if this infects a cell in my nose or in my arm, as this cell experiences mitosis, all of its offspring-- but its offspring are genetically identical-- are going to have this viral DNA. And that might be fine, but at least my children won't get it. You know, at least it won't become part of my species. But it doesn't have to just infect somatic cells, it could infect a germ cell. So it could go into a germ cell. And the germ cells, we've learned already, these are the ones that produce gametes. For men, that's sperm and for women it's eggs. But you could imagine, once you've infected a germ cell, once you become part of a germ cell's DNA, then I'm passing on that viral DNA to my son or my daughter. And they are going to pass it on to their children. And just that idea by itself is, at least to my mind. vaguely creepy. And people estimate that 5-8%-- and this kind of really blurs, it makes you think about what we as humans really are-- but the estimate is 5-8% of the human genome-- so when I talked about bacteria I just talked about things that were along for the ride. But the current estimate, and I looked up this a lot. I found 8% someplace, 5% someplace. It's all a guess. I mean people are doing it based on just looking at the DNA and how similar it is to DNA in other organisms. But the estimate is 5-8% of the human genome is from viruses, is from ancient retroviruses that incorporated themselves into the human germ line. So into the human DNA. So these are called endogenous retroviruses. Which is mind blowing to me, because it's not just saying these things are along for the ride or that they might help us or hurt us. It's saying that we are-- 5-8% of our DNA actually comes from viruses. And this is another thing that speaks to just genetic variation. Because viruses do something-- I mean this is called horizontal transfer of DNA. And you could imagine, as a virus goes from one species to the next, as it goes from Species A to B, if it mutates to be able to infiltrate these cells, it might take some-- it'll take the DNA that it already has, that makes it, it with it. But sometimes, when it starts coding for some of these other guys, so let's say that this is a provirus right here. Where the blue part is the original virus. The yellow is the organism's historic DNA. Sometimes when it codes, it takes up little sections of the other organism's DNA. So maybe most of it was the viral DNA, but it might have, when it transcribed and translated itself, it might have taken a little bit-- or at least when it translated or replicated itself-- it might take a little bit of the organism's previous DNA. So it's actually cutting parts of DNA from one organism and bringing it to another organism. Taking it from one member of a species to another member of the species. But it can definitely go cross-species. So you have this idea all of a sudden that DNA can jump between species. It really kind of-- I don't know, for me it makes me appreciate how interconnected-- as a species, we kind of imagine that we're by ourselves and can only reproduce with each other and have genetic variation within a population. But viruses introduce this notion of horizontal transfer via transduction. Horizontal transduction is just the idea of, look when I replicate this virus, I might take a little bit of the organism that I'm freeloading off of, I might take a little bit of their DNA with me. And infect that DNA into the next organism. So you actually have this DNA, this jumping, from organism to organism. So it kind of unifies all DNA-based life. Which is all the life that we know on the planet. And if all of this isn't creepy enough-- and actually maybe I'll save the creepiest part for the end. But there's a whole-- we could talk all about the different classes of viruses. But just so you're familiar with some of the terminology, when a virus attacks bacteria, which they often do. And we study these the most because this might be a good alternative to antibiotics. Because viruses that attack bacteria might-- sometimes the bacteria is far worse for the virus-- but these are called bacteriaphages. And I've already talked to you about how they have their DNA. But since bacteria have hard walls, they will just inject the DNA inside of the bacteria. And when you talk about DNA, this idea of a provirus. So when a virus lyses it like this, this is called the lytic cycle. This is just some terminology that's good to know if you're going to take a biology exam about this stuff. And when the virus incorporates it into the DNA and lays dormant, incorporates into the DNA of the host organism and lays dormant for awhile, this is called the lysogenic cycle. And normally, a provirus is essentially experiencing a lysogenic cycle in eurkaryotes, in organisms that have a nuclear membrane. Normally when people talk about the lysogenic cycle, they're talking about viral DNA laying dormant in the DNA of bacteria. Or bacteriophage DNA laying dormant in the DNA of bacteria. But just to kind of give you an idea of what this, quote unquote, looks like, right here. I got these two pictures from Wikipedia. One is from the CDC. These little green dots you see right here all over the surface, this big thing you see here, this is a white blood cell. Part of the human immune system. This is a white blood cell. And what you see emerging from the surface, essentially budding from the surface of this white blood cell-- and this gives you a sense of scale too-- these are HIV-1 viruses. And so you're familiar with the terminology, the HIV is a virus that infects white blood cells. AIDS is the syndrome you get once your immune system is weakened to the point. And then many people suffer infections that people with a strong immune system normally won't suffer from. But this is creepy. These things went inside this huge cell, they used the cell's own mechanism to reproduce its own DNA or its own RNA and these protein capsids. And then they bud from the cell and take a little bit of the membrane with it. And they can even leave some of their DNA behind in this cell's own DNA. So they really change what the cell is all about. This is another creepy picture. These are bacteriaphages. And these show you what I said before. This is a bacteria right here. This is its cell wall. And it's hard. So it's hard to just emerge into it. Or you can't just merge, fuse membranes with it. So they hang out on the outside of this bacteria. And they are essentially injecting their genetic material into the bacteria itself. And you could imagine, just looking at the size of these things. I mean, this is a cell. And it looks like a whole planet or something. Or this is a bacteria and these things are so much smaller. Roughly 1/100 of a bacteria. And these are much less than 1/100 of this cell we're talking about. And they're extremely hard to filter for. To kind of keep out. Because they are such, such small particles. If you think that these are exotic things that exist for things like HIV or Ebola , which they do cause, or SARS, you're right. But they're also common things. I mean, I said at the beginning of this video that I have a cold. And I have a cold because some viruses have infected the tissue in my nasal passage. And they're causing me to have a runny nose and whatnot. And viruses also cause the chicken pox. They cause the herpes simplex virus. Causes cold sores. So they're with us all around. I can almost guarantee you have some virus with you as you speak. They're all around you. But it's a very philosophically puzzling question. Because I started with, at the beginning, are these life? And at first when I just showed it to you, look they are just this protein with some nucleic acid molecule in it. And it's not doing anything. And that doesn't look like life to me. It's not moving around. It doesn't have a metabolism. It's not eating. It's not reproducing. But then all of a sudden, when you think about what it's doing to cells and how it uses cells to kind of reproduce. It kind of like-- in business terms it's asset light. It doesn't need all of the machinery because it can use other people's machinery to replicate itself. You almost kind of want to view it as a smarter form of life. Because it doesn't go through all of the trouble of what every other form of life has. It makes you question what life is, or even what we are. Are we these things that contain DNA or are we just transport mechanisms for the DNA? And these are kind of the more important things. And these viral infections are just battles between different forms of DNA and RNA and whatnot. Anyway I don't want to get too philosophical on you. But hopefully this gives you a good idea of what viruses are and why they really are, in my mind, the most fascinating pseudo organism in all of biology.