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[music] Hello. Good afternoon. Anyway, welcome to Vyology. I am Vincent Rakinello and I will teach this whole course myself. I've been doing this for 15 years. I'm a veriologist.
Virologist Vincent Rakinello introduces viruses: their vast numbers in oceans, whales, and humans, and their ubiquity in and on the body. Course opener.
Key Takeaways
- Viruses are extraordinarily abundant and present in nearly every environment on Earth.
- Humans harbor many viruses, including integrated and persistent ones, and a complex virome.
- Viruses play important ecological roles beyond causing disease.
- Viral diversity and rapid evolution pose challenges for antiviral drugs and vaccines.
What the video covers
- The lecturer, a virologist with 15 years of experience, introduces the course and his enthusiasm for viruses.
- Viruses are everywhere: humans breathe them in, eat them in food, and carry integrated viral DNA in their genomes.
- Ocean bacteriophages number over 10^30 particles, with a combined mass exceeding that of all elephants by a thousandfold.
- Whales are infected by viruses related to human neuroviruses, and whale feces release vast numbers of these viruses into oceans.
- Viruses make up about 94% of all particles in seawater and play a major role in biogeochemical cycling.
- HIV genome pools already contain resistance to all current antivirals, illustrating the power of viral numbers.
- Nearly all adults carry herpesviruses acquired in childhood, and the human body hosts a 'virome' across brain, respiratory, digestive, and skin systems.
- Drone-based sampling of whale breath has revealed many viruses, showing viruses can be found in essentially every environment.
- Viruses are reclassified as parasites that take resources from host cells, and some may be beneficial, though this is hard to test in humans.
- Historical context is given: Pasteur's view of viruses as microbes, early discoveries like rabies, and the development of modern virology techniques.
Chapters
- 00:00Introduction and course overview
- 02:59Viruses in whales and marine environments
- 06:06Human herpesviruses and the human virome
- 09:15Viruses in plants, food, and beneficial roles
- 12:15Virus evolution, numbers, and the virus-host relationship
- 17:20Historical discoveries and the origins of virology
- 25:20Virus classification and structure
Full Transcript — Download SRT & Markdown
Speaker A
I used to have a lab at the medical center. I closed it three years ago and now I teach and do some other things.
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So, I love viruses. They are amazing. And at the end, I want you to love them, too. I don't love getting sick. We live and prosper in a world of viruses.
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They're everywhere. This room is teeming with viruses because each of you are breathing six lers of air a minute. And you all have viruses. There's no exception. We're full of beneficial and non-beneficial viruses. And we'll talk more about that. We eat virus particles
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in our food. We breathe them in. As I say, of course, if you're in a room with no one, you're not breathing in viruses.
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But if you're here or if on a subway or some other crowded place, you're breathing in other people's viruses. And we even have viruses as part of our genetic material. They're integrated into our DNA. Over 90% of you have
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viruses integrated. Well, actually 100% of you have viruses integrated into your DNA. And many over 90% of you are carrying a variety of different viruses.
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Now viruses just move around randomly. you say for example you exhale them they're carried by currents and they randomly bump into perhaps a host and start another infection. So in order to do that they have to make lots and lots of particles
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and the number of viruses on earth is amazing. If you just look in the waters of the earth mainly the oceans there are over 10 to the 30th virus particles that infect bacteria. These are called bacteria phages.
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And that's a huge number, right? It's bigger than avagadro. So what does it really mean? Well, each bacteria phages 10 the minus15 femp grams or femptogram. So if you multiply that times 10 the 30, you see that the
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mass of viruses, bacteria phages on earth exceeds that of elephants by a thousandfold. And these are things you can't even see. So that's amazing, right? And secondly, if you line up these viruses head to tail, they go 100 million lighty years right
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past the nearest galaxy. It's amazing. And think this is just in the oceans. Just the viruses, the bacteria phages in the ocean. So numbers is their game.
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Whales, for example, are commonly infected with viruses that we call kissy viruses. These are related to human neuro viruses, the cruise ship virus, which we'll talk about later. And these viruses make whales sick.
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And they can have rashes and blisters and gastroaneritis. And these viruses can also infect humans. But whales excrete, one whale excretes 10 to the 13th kissy viruses every day in feces because this is a gastrointestinal virus. huge numbers of
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viruses going into the oceans. Now, in the oceans, there are many, many virus particles, and that's shown on this slide. I like to say that viruses are not just purveyors of back bad news.
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They're actually very useful in different ecosystems. As you'll see now, in a liter of coastal seawater, there are more virus particles than people on Earth. Everywhere you go, the oceans are full of viruses. Of course, it gets less
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and less abundant as you go deeper and deeper, but you can go all the way to the deepest parts of the oceans and you will find viruses because there is life at the bottom of the seas as well. Now,
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these two pie charts illustrate how big a factor viruses are. On the left, we have biomass. We're looking at proarotes, protests, and viruses. So, you see the proarotes exceed the biomass of everything else. But if you look at
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abundance just the number of particles in the ocean viruses are the are the players 94% of all particles. So the the viruses in the oceans are very abundant. What do they infect? Fishes, mammals, protests, plankton, all of these single or
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multisellular organisms floating around. And they actually play a big role in what I call biogeeochemical cycling. the turnover of organic material and the liberation of carbon and and other elements as well. So they're really really important for that. But this is a
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course mainly focused on human viruses and so we're not going to talk much about that but I want you to know they're really environmentally important. Now there are also 10 to the 16th HIV genomes on the planet. human
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immuno defficiency virus of course the causitive agent of AIDS which we will talk about later we know how many million people 37 million people are infected how many genomes they have each and that's the number you get it's also
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a big number and what that number means for example is in that pool of genomes there's already resistance to all of the antivirals we have against HIV we have about 40 which are very effective in triple combinations but there's already
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resistance in this huge genome pool. And if we make 10, 20, 100, a thousand antivirals in the coming years, there's already resistance to all of those as well. That's how big this number is. So that's again the the effect of numbers
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on viruses. So how infected are we? Well, all of us have at least uh these herpes viruses. Herpes simplex one and two Vicelazaster chickenpox uh human cytoomegala virus, epstein bar and then HHV 6,7 and 8. And these herpes
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viruses are large envelope doublestranded DNA viruses that infect you in your first 10 years of life and then you remain infected for the rest of your life. So over 90% of you cerological surveys have shown that over 90% of us are serositive for these
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viruses and the consequences we'll talk about in a specific lecture on this. We each have in addition to these herpes viruses what we call a vyro. You've heard of the microbiome, right? All the bacteria that live and on us in and on
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us. Well, we have a vyro. And people have studied this. And here is a picture on the left which shows you the DNA and RNA viruses that are in and on us. So viruses unlike anything else on the
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planet can have genetic material of either DNA or RNA. That's right. And so we have DNA viruses in blue and RNA viruses in green. So these are basically sequenced based estimates. We don't know how many of these are actually
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infectious. But you can see nervous system. You have viruses in your brain. Respiratory tract lots. Your genital tract, blood, digestive tract, even your skin and hair and nails have viruses on them. So you cannot get away from them.
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All right? That's why you need to take this course and understand it. But new technologies have made it possible to discover uh viruses everywhere even in Wales. So here is a drone based study looking at the breath of whales uh when
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they sound when they not not sound when they come to the surface. What is that called? What's the word for that? Coming to the surface. breach. Thank you. Um, when they breach, you don't take a breath. So, this is a drone. It's got a
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petri dish on it. And this is actually a movie. And this is off the southern coast of Australia. And there's a scientist running the drone. And when the whales breach, they open up the um the petri dish. So, let's see if it
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works. Let's try. Oh, there it goes. Did you see it? I'll do it again.
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So the thing is opening up just as they breach. It's collecting the droplets. They bring them back to the lab. They extract nucleic acid and they can sequence it and you find lots and lots of viruses in whale breath. Now that's
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not the best, right? It's just their breath because it may not represent everything in them, right? viruses in the blood may not necessarily be in the breath, but it's the best you can do because they're not going to swim next
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to your boat and let you take samples from them, right? And if you find a whale on the beach dead, it's too late.
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So, this is a pretty good way of getting an estimate of what's in whales. And we can look, we're interested in looking everywhere. We look in every living thing on Earth, dirt, water, every rocks even, and we find viruses everywhere.
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There's nothing that escapes them. And as I said earlier, even our human genome has viruses integrated into them. This is a pie chart of the 3.2 billion base human genome. And you can see one and a half% is protein coding which is really
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remarkable. And then there are many other sequences but the ones that uh we're going to talk about in this course are these here labeled LTR retro transposons. 8 8% these are viruses basically viral genomes integrated into your DNA most of which are silent but
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some of which have been actually repurposed to do other things and we'll we'll talk about that later and every animal on the planet every living thing on the planet seems to have viruses integrated into their DNA because viruses are quite ancient okay
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so why are we okay right we have all these viruses is in us and around us.
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So, everyone here looks pretty okay. I I feel good. Why is this? Well, there are a couple of reasons.
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First of all, most of them pass through us. We inhale them and they don't do anything and we eat them and they pass through us. Here's some example of ingesting viruses. Cabbage.
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Here's there's a study done in marm in Washington DC. uh and they analyzed cabbage for viruses and they found each serving which would be like klelaw there 100 square centimeters of leaf would have 10 to the eighth virus particles of
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what's called a bulo virus. These are viruses that are drawn there that infect insects. In particular the cabbage looper that larvae there that crawls over cabbage and you know cabbage grows in fields. These caterpillars crawl all over it and you cannot wash it well
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enough to get the viruses off. So next time you eat cabbage, you're eating viruses. But they pass through you because they're insect viruses. They're not viruses that can infect human cells.
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A [clears throat] similar way if you look at RNA viruses in human feces, uh you can find lots of them. Most RNA virus sequences in our poop is similar.
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are similar to to viruses that infect plants because we ingest a lot of vegetables. At least we should. That's good for you. And those vegetables all have their own viruses. The most common RNA virus in our feces is peppermild
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model virus. You can say that at a party now. Do you know what the most common viruses in your feces? 10 to the 9th virus particles per gram of dry feces.
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There's a pepper with an infection, his skin gets crinkly. So, we eat a lot of peppers and so we have a lot of it in our feces. There is a company that exists you can send your feces to and
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they will sequence it and tell you what viruses are in it. I get emails all the time from people who are very frantic. I have peppermild model virus. What should I do? And there's nothing to do because it won't infect you. So these are
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examples of viruses passing through you. There are beneficial viruses for other species. I'll give you a couple of examples. Here on the left is a grass that grows at high temperatures. It's it's called danthelium lenuosum. If you've ever been to hot
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springs like Yellowstone, you see grasses growing on the edge. These are these thermmo tolerant grasses. They can withstand high temperatures like 55 uh degrees Celsius. Their thermal tolerance derives from a symbiotic relationship with a fungus and a virus in the fungus.
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So these plants are full of fungi curvularia protuberada and those fungi are infected with viruses and both are needed for thermlerance. If you take the virus out of the fungus it's it's not good enough. So that's obviously a
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beneficial virus. the virus gets a place to multiply and the plant gets to live at high temperatures. On the right is a virus that's beneficial for parasettoid wasps. Uh these are creatures that inject their larae into caterpillars and they hatch
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and the little the baby wasps eat the inside of the caterpillar and then burst out. This is the original alien movie, right? It was in nature many years before.
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But what's really cool is that along with the larvae, here's a wasp egg being injected by the parasettoid wasp. It also injects [clears throat] viruses.
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They're called polyidna viruses. Those viruses are encoded in the genome of the wasp. So the wasp produces the particles. They're injected into the caterpillar and then they imunosuppress the caterpillar so it will not reject the wasp eggs. Isn't that great? I mean,
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nature is amazing. Nature is the greatest genetic engineer. So, two examples of beneficial viruses. This is beneficial for the wasp, not the caterpillar, unfortunately. And then one more. We have an example of a beneficial virus in in a mouse because we really
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can't do these kinds of experiments in humans. So we don't know which of our viruses are beneficial. But in a mouse we're looking at this the intestine here the small intestine. This is a conventional mouse. The intestine looks
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lovely. Nice morphology villi. And then if you stain for lymphosytes part of the immune system they're staining brown.
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You can see the intestine has a very nice immune system. Now you can grow mice in germfree situations where they have no bacteria in their guts. They're called germfree or GF. And you can see the villi are a bit abarent and there
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are no lymphosytes there. So there's a defect in development of the gut and the immune system. But if you infect these germfree mice with murine neurovirus, it's a calissi virus related to those that infect whales, it partially restores the function lost by being
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germfree. The villi are a little bit more normal and you have some lymphosytes uh in the intestine. So that's really the best example in mammals anyway of beneficial viruses.
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Now, since we're full of them and we seem to be okay most of the time, we assume that some of these viruses in us are beneficial, but we haven't been able to yet uh address that question. The other reason why
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most viruses don't affect us, right, besides passing through us and being [clears throat] beneficial perhaps is that we have a great immune system. As many of you may know who have taken an immunology course here or elsewhere, it's an amazing system that
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is designed to protect us against pathogens. And we will talk a little bit about immunology in two lectures of this course in terms of understanding how it regulates virus infections.
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And so if you have any kind of condition that imunosuppresses you, if you have if you're [clears throat] getting an organ transplant, you get imunosuppressive drugs. If you're infected with an imunosuppressive virus like HIV or measles virus, your
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immune system is down and suddenly the most benign viruses will cause problems in you. So it shows that our immune system is really important for keeping most of them in check. And when you get infected with pathogens like influenza
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virus and SARS KV2, the reason most of us survive is because our immune system takes over.
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Now we have viruses in it's not all viruses make us sick of course as I think you're getting the message. This virus is a polyoma virus. We'll talk about it later which infects everybody.
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Doesn't seem to cause any disease but it can be used to track human migration. So this is a map of human migration out of Africa into Europe and Asia and the Americas. So the dotted purple line is the migration that you can track using
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human genome sequences. Okay. You can also track human movements using whether people have been infected with a polyoma virus. There are different kinds of polyoma viruses. They're spread within families. They tend to be family specific and geographically specific. So
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you can actually map human uh population movements out of Africa even in even more detail than you can with the genome sequence. You can see moving out of Africa into Europe all the way down to Australia and all the way down into
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South America. So this is what you can do with a virus that infects everyone.
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Viruses also play a big role in shaping host populations and vice versa as well.
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Of course, if a virus eliminates its host, that's the end for the virus as well. So, there always has to be a balance. This is a story in the ocean.
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And those that [clears throat] white stuff that you see that's in the ocean is taken from a satellite. This photograph uh this is uh I forget where this is somewhere in Europe. I I can't remember. But um the white stuff is are
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ocean blooms of a ukareotic phytolanton. And these occur periodically when the sun is shining brightly because they're photosynthetic and they multiply. But then within a week or so after the blooms, the algaal blooms, they disappear because there's a virus
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amongst them that infects them and lices them. So the virus controls these algoloom populations. And so this is just an example of how this works in a kind of a stunning way, but this happens with all populations. So in in short,
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I've tried to give you a little uh introduction which tells you that viruses are just amazing.
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And most importantly, these are two viruses that we're going to talk about during this course. They're beautiful.
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We know structures of many of them. Viology is an integrative science. It means you need to know a lot of things to understand viruses.
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So if you want to be a chemist, you study chemistry and maybe physics and thermodynamics. But with viruses, you have to know everything. You have to know biology, biochemistry, cell biology, organic and inorganic chemistry. You need to know sociology to
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understand how populations interact. epidemiology many many sciences go into understanding viruses that's why I call it an integrative science and I think it helps you to understand other sciences well also so if you don't get biology if you study viruses I think you will get
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it because you have to understand biology to understand how viruses work so in this course my goals are to give you a big picture view of viology I'm not going give you a lot of details about a bunch of different viruses that
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doesn't help you. I want to give you an overview of what happens. In the first half of the course, we're going to talk about what happens when viruses get into cells and make more viruses. And then the second half, we'll talk about how
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viruses get into hosts, make them sick. And so, it's about teaching you an integrative overview of viruses, not just a little bit about flu, a little bit about herpes, and so forth. You're not going to learn enough by doing that.
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You will. The problem that most people have, why they're afraid of viruses is they don't understand it, right? Fear usually comes from misunderstanding.
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And so, you're going to learn enough about viruses in this course so that you're no longer going to be scared.
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You're going to be able to figure it out. You're going to be able to look in newspapers or online news and say, "That's bull. That can't be right what they are saying." And in fact, I try to stay away from politics because
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you know when you mix politics with science, do you know what you get? You get politics sadly. And politicians are messing with our science these days. And here's some headlines from the past few years. Uh just to illustrate that at the
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beginning of the COVID pandemic, I was teaching this class January 2020 and every class I would put up a map and it had more and more dots showing more and more cases. And we got to March spring break. I could not believe a
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virus interrupted my viology course. [clears throat] Anyway, here's a headline. Uh corona virus could mutate. I'm going to tell you in this course why that's the most absurd statement in the world. It's like saying the earth is round and making
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that a headline in a newspaper. Viruses are always mutating. Another one right there. Uh people don't understand the relationship between viruses and immunity.
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Vaccines do not prevent infection. They prevent disease. And people thought they would prevent infection. And when that started happening, they said the v the vaccines were no good. So, we can talk about that later. And then more recently, it's become politicized
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because, well, you can get votes by being anti-science. And you probably have heard a lot about so-called gain of function research. And the current administration has severely restricted this kind of work, which is absurd because it's essential to all
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kinds of scientific research. And we'll talk a little bit about that as well. So, I want you not to only understand how viruses work. I want you to understand how they interact with society.
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I think we can do that. All right. So, I'm going to use these quizzes and I won't see your individual answers. It will not count for your grade. This is just to see if I'm explaining things to you properly. Which statement is true?
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All viruses make us sick and can be lethal. Our immune system can manage most viral infections. Humans are usually infected with one virus at a time.
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The press is usually correct in their viology reporting. Our immune system cannot handle most virus infections. So, normally I get a graph and you can see your progress, but I screwed something up. So, we'll have to wait till the next
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one. Most of you are getting number two. Our immune system can handle most viral infections because number one, all viruses make us sick.
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you would very few people took that. Humans are usually infected with one virus at a time. I told you have lots of herpes viruses in you. The press is usually correct in their viology reporting.
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Nobody took that one. Nobody took that bait. Actually, one person did. All right. Finally, we can answer the question. What is a virus?
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This is my current definition. And a virus is an obligate intracellular parasite. It has genetic material, DNA or RNA. It has a protein coat. That's the minimal virus. And sometimes it has a membrane around it. Not all viruses
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have that. So let's break this down. Infectious. You probably understand that it can go from host to host. Obligate intracellular parasite. So it has viruses have to get inside of cells in order to reproduce. They cannot reproduce outside of a cell. If I give
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you a tube of viruses, they will not reproduce in that tube unless there are cells in it. So that's what obligate intracellular means.
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Parasite, a parasite is something that takes away resources from another organism. And so par viruses take a lot from the host cell and and often they damage them. So they're clearly parasites. And so here are some [clears throat and cough]
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examples of viruses. Here is my favorite virus here, [clears throat] polio virus, because I spent 45 years working on it. It is made of pure protein with an RNA genome.
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There's no membrane. Here is SARS KV2. [clears throat] It is an RNA virus and it has an envelope around it. We'll go into the structure of viruses in more detail later on, but you can see there's quite an array of different structured
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viruses, but they all fit uh this common definition. Now, viruses, as we just defined, are obligate parasites, which [clears throat] means they need functions from the host.
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So, if you study viruses, you are going to learn about the host as well. And so many important discoveries on cells have been made by using viruses as probes. Uh for example, the basics of DNA replication were studied with viruses.
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mRNA splicing was study was discovered with viruses. Capping and polyventilation were discovered with viruses just to name a few. You always learn about the host because you have to use a host, a cell or an organism in order to study viruses.
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So, are viruses alive? Maybe some of you are wondering. Here's how I answer that question. Virus is an organism with two phases. One phase is the virus particle.
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All right? The I use a specific name for the virus particle. I call it a virion if it's infectious because as you'll see later not all virus particles are made infectious. So the virion is one phase of this organism. The viron is not
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living. If you put a virus in a tube as I said before it will not do anything.
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It will not multiply. It will not evolve. It will not make energy. So it's not living. But if you infect a cell with the virus, then the cell is turned into a virus producing factory. It takes over all the
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uh mechanisms that are going on inside of a cell. It's an infected cell. So it is a virus infected cell that's of course living. So that's how I get at this question. The virus particle is not living, but of course the infected cell
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is. One thing I want to give you a warning about early on here is be be careful characterizing viruses anthropor anthropomorphically.
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Okay, which means don't give them human qualities because they're not. And we don't know what is driving virus replication and evolution. So viruses do not think people I hear in the press this is very common to do because it's
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very easy to assign features to viruses. The virus thinks it's going to do this.
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The virus is attempting to do this. All of that's wrong because they're passive agents. They don't try to do anything.
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As I said, they come out in your breath and they just bounce around until they hit something. And if they don't hit something, that's the end. They're finished. So there's no active thought in doing anything. So they don't achieve
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their goals in a human centric manner. People will say, "Well, I think the virus is trying to do this." You shouldn't say that because you're applying human values to the virus and you don't know if that's true. And so
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the reason I don't want you to do this be is because it will bias your thinking about how viruses work and how they have evolved. Okay? And maybe from time to time I will make that mistake as well,
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but I try not to because it's really not a good thing to do, okay? But I'm not going to take points away from you if you do it. I'm just telling you that that's how you should look about
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viruses. Now, viruses are very small. Here are some pictures to give you a sense. Here's an E.coli at 100,000 magnification. This has a bacteria phage on it. So, you can see the fage is rather small compared to the host.
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Here's HIV1 in D. Uh here is tobacco mosaic virus, a long rod-shaped virus. So you can see they're quite small. And then there's a panel here which is expanded. So now we have a millionfold magnification and you can see uh here polio virus in H
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and all of these others are molecular bits from cells. Here's a ribosome in G.
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So you can see polio virus is about the size of a ribosome. Here is an antibbody in F, a tRNA in uh E, and then A is supposedly a carbon atom, but it's it's probably much smaller than that. So,
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viruses are are very small, although we used to think they are they were smaller than we know now.
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In fact, you could put a lot of viruses on the head of a pin. You could put 500 million rhino viruses, which are about the size of a ribosome. And so, you know, when you sneeze, you're expelling enough viruses to infect thousands of
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people. By the way, on the top of this um pin here, this is a dustmite, so it's very large. And then in this middle is the collection, including viruses. We have red blood cells and we have a a
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lymphosy and some yeast. And then uh the virus is here. It's an Ebola virus, so it's quite long. It's in the middle. So, it's very very tiny compared to everything else. But we used to think viruses were all rather tiny until about
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20 years ago. Uh the discovery of what are now called giant viruses. These were originally mimi virus was the first one to be discovered. You can see how much bigger it is than HIV or rhino virus particles. And so this giant viruses is
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not a formal classification. It's just a way to point out that these are bigger than we had expected and in their genomes are also very big and we'll talk about the consequences of that uh next week.
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So here's an example of a giant virus. Uh this one is called Pandora virus.
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Uh here's here's a reconstruction of an electron microraph of the virus. It's about one micron in length. That's huge for a virus. You can actually see them under the light microscope. Most viruses are submicroscopic. You need an electron
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microscope to see them. But Pandora viruses and many of the giant viruses are really big. And that's compared to a bacterium here on the bottom, which is about two microns in length. It's about twice the size of that Pandora virus. By
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the way, they're called Pandora viruses because when the genome was sequenced, it's something like two and a half million base pairs of doublestranded DNA. It 90% of the proteins had never been seen before. They were all new. And
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so it was like opening Pandora's box. Now viruses are also different from bacteria in that they replicate by assembly of preformed components. Bacteria undergo binary fision in all cells of course. So here is an example of bacteria multiplying. You take a single bacterium
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and you put it in broth and then you measure with time the number of cells and you can see they soon start to double and increase. And so one bacterium becomes two and four and eight and so forth. So that's binary fision.
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Viruses do not do that. Viruses get into cells and make parts that are then assembled to make new virus particles.
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So if you infect cells with a virus and then you measure with time the number of infectious particles, you'll see that for a period and that depends on the virus. you can't detect any new virus particles and that's very different,
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right? The bacteria start to divide right away. That's because the genome of the virus has entered the cells and it's directing the synthesis of new virus particles and then when those are made then they can finally be released and
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you have a a burst of infectious virus particles. So fundamentally different from bacteria and all other cellular life when they were first discovered which the following is true concerning bacterial versus viral replication.
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Viruses assemble using preformed components. Bacteria do not replicate via binary fision as viruses do. Bacteria assemble using preformed components. Viruses do not have an eclipse period. And viruses replicate by binary fision. All right, let's see what we got here. So now I can
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show the results and you can see how you have done. Okay, let's see. So 90% of you got a viruses assemble using preformed components. That's the correct answer. The others, they [clears throat] do not. Bacteria do not replicate.
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That's wrong. They do replicate by binary fision. Bacteria assemble using preformed components. No, they do binary fision. viruses do not have an eclipse period.
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So, some of you may have missed that, but on this slide, there's there's this period when when you infect cells with a virus, there's a period when there's no new infectious virus detected. That's called the eclipse period. So, they obviously
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do have an eclipse. How old are viruses? [clears throat] We have a number of ways we can answer this question, and we'll talk about that in a in a separate lecture on evolution.
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But current estimates put some viruses, particularly retroviruses, about 450 million years ago in the Orvisian period. That's right here when we have the first uh land plants.
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Uh and um these may have been infecting organisms in the oceans. It's not really clear, but I think 450 million years is probably a low estimate. Probably viruses are older. It's just hard to date them any older. We don't have
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fossils, of course, but we do think that the ancestors of viruses originated billions of years ago as soon as the earth cooled and chemicals began to form self-replicating RNA like molecules arose and those were the precursors to viruses and we again
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we'll talk about that in another lecture. Now if we move closer to the present we can see references to viral diseases in the historical record. So here this um 700 BCE the Iliad has a phrase here this fire brand raid
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Hector leads the charge. So rabies of course is a virus disease. They didn't know it was viral at the time but obviously it was given the name rabies.
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And on the right is an Egyptian carving from about 1500 BCE showing a priest with a a leg that looks like uh he had polio. It causes flaccid paralysis of the leg. So viruses have been around for many years, but it's only recently that
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we've had the ability to study them. [clears throat] Vaccination to prevent virus disease is also quite old. in China in the 11th century uh to prevent smallpox the practice of varilation was done. So people noticed smallox virus of course
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is a highly lethal virus and it was noticed that if you got smallox and survived you never got it again. They didn't know what caused it but they said well um maybe we can give it to people and it will protect them against
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disease. So they would take the pestules which arise all over your body, grind them up, and here you can see they're blowing them into this person's nose.
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It's a it's an ancient form of immunization. About 10 to 20% of the people died, so not a good safety profile, but the rest were protected against smallox. And this procedure actually spread globally. uh Lady Montigue who was the wife of the British
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ambassador to Turkey discovered it being used there in the 1700s. She brought it back uh to the UK and of course in the 1790s then Edward Jenner did a formal experiment with an N equals 1, one child to show that vaccination can prevent
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disease and we'll talk about that later. [clears throat] Now the modern era of viology originates with three individuals here. Lyven Hook who made the first really good microscopes and he saw that in water and other fluids there were small things.
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You know there was a time in history when people thought everything that existed is what you could see and there was nothing smaller. But he shattered that and found microorganisms.
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uh Louie Pastor working in the 1800s discovered that bacteria could do good things. They could ferment and make wine and cheese and so forth.
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And then Kulk in the later 1800s associated bacteria with specific diseases. So from this we have this concept that there are microorganisms very tiny entities that can cause disease.
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Now [clears throat] the term virus comes from the Latin. It means poison. So it was thought to be a liquid. And so anything that caused infectious disease that is from person to person was called a virus in the 1700s for example. And
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Louisie Pastor basically said every virus is a microbe. Remember Louis pastor didn't know about viruses as we know them today. He just knew about bacteria. So he said every virus is a micro. So we have this idea that a virus
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is just an agent causing infectious disease. But we haven't actually identified viruses yet. That came later.
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This fellow Chamberlain was working in the lab of Louis Pastor and the water was contaminated and he wanted to clean it up. So he devised this porcelain filter. So you would he made this filter which had very small pores and you apply
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it a vacuum to it. You can put liquid in the top. You you apply a vacuum. The liquid will go through the filter and it'll be it will remove all the bacteria.
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And in the in the um ptor lab, they found that the agent of rabies that caused rabies in animals passed through this filter. So pastor said, "Ah, it's very small. That's all there is to it." But later at the end of the uh 1800s,
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a disease was destroying the tobacco crops of Europe. So this is a tobacco leaf. Tobacco was already a big uh product back then. And there was a disease going around that made the leaves modeled and therefore not good to
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sell. So people wanted to know what was causing this disease. So they ground up the leaves and they put them through one of Chamberlain's filters and they found that the agent went through the filter.
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So again, very small. So two independent groups discovered this with tobacco mosaic virus in 1892 and 1898 that the agent of the disease passed through filters that retain bacteria. Today you can buy these of course in the laboratory.
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[clears throat] This is originally Chamberlain's flask here. You can buy them with different pore sizes and 0.2 microns became the standard for identifying viruses. So if an agent could go through a 02 micron filter, it was considered in 1898 the agent of foot and mouth
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disease was shown to be filterable. This is a now we know it's a virus that causes disease in cattle uh and is agriculturally important.
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But in addition to it being small, what was emerging was the idea that these agents will not replicate in broth. They need a host. So tobacco mosaic virus you have to put on the leaf in order for it
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to multiply. Foot and mouth you have to put in the the cattle for for it to micro um multiply, but they were still thought to be liquids at the beginning of the 1900s.
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Now, using this technology, people started to discover a lot of viruses, and this was driven by disease.
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1901, yellow fever virus, right? They're digging the Panama Canal. People are dying of this disease. They figure out it's a virus. Rabies virus, 1903, smallox, 1906, etc. um all driven by discovery of disease-causing agents, but they're still called filterable viruses
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because they're thought to be liquids. But in 1939, the first electron microraphs of viruses were taken by Helm Ruska who built the first scope in 1933. And lo and behold, they were they turned out to be particles. Here are bacteria phages
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attached to a E.coli. coli. The the viruses are not liquids, they're particles. So, this gets rid of the idea that they're liquids. Finally, they're just called viruses around 1940.
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Okay, next question. This is the last one. Which is a key concept first discovered about viruses that distinguish them from other microorganisms? They were too large to pass through a 2 micron filter. They could replicate only in broth. They made
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tobacco plants sick. They were small enough to pass through a 02 micron filter. None of the above. All right, let's have a look.
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[clears throat] Most of you picked D. They were small enough to pass through a 02 micron filter. That's the right answer. So, what's the key concept? They were too large to pass through a 02 micron. No, that's that would be
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bacteria. Nobody picked B. That's good. They made tobacco plants sick. They did, but that's not a defining feature of a key concept that distinguished them from other bacteria. So that's why D is the answer. So after the electron microscope
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was developed, people started taking pictures of different viruses, and we can see they're really particulate. Here was tobacco mosaic virus, which turned out to be a rod-like particle. We'll come back to that later. Here's a a bacteria phage. Here's rabies virus and
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polio virus. And so you can see they're clearly particulate. And in addition to the electron microraph for showing that viruses are particles, not liquid, this experiment, which I've already showed you was the other proof, right? They're not just simply small bacteria. Because
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that's what Pastor thought actually. He thought they go through the filter, but they're just small bacteria. But no, they were something new. So remember, you would you add a bacterium to broth, it begins to divide almost immediately within a few minutes. But if you add
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viruses to cells, there's an eclipse period where you don't see any new virus particles made because the virus is putting its nucleic acid into the cell.
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The nucleic acids being expressed and proteins are being made. And finally, when new particles are assembled, they leave the cell. So they are not just small bacteria. there's something unique and finally we have that established for viruses.
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Now today we know a lot about viruses. We know structures of many viruses and we'll talk about that in in a lecture on its own. Uh so for example this is polio virus. In the background is an electron
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microraph. On the right is a lowresolution cryo picture and on the top left is a picture derived by X-ray crystalallography. And we can do these for many viruses as you'll see uh in this course.
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We classify viruses now uh very precisely so we know what we're talking about. The main classification determinant is the nucleic acid sequence. So now if you isolate a new virus, you know, January 2020, we isolate a new virus causing a
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respiratory disease, we sequence its genome and we can see it's a corona virus because we have a database of all virus sequences that we can use to compare it. But also the nature of the protein shell, whether there's a
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membrane and the dimensions play somewhat into classification, but the nucleic acid sequence is really the king.
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Now when we classify viruses, you may see these some of these words used and I want to explain them to you uh now and there's a very nice website that will [clears throat] explain all of virus classification to you but basically the
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top level classification of viruses are called realms. All right and those words end in vira.
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So for example all the RNA containing viruses are classifi classified in the realm riboia and then the DNA viruses has have a bunch of different realms here that you can see monadnaveria veridia etc. Okay. [clears throat] So that's the highest level and below that
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we have fila which are ending in virota like art art ver art art vidot duplora vir etc.
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Yeah they're really hard to pronounce. I have problems too with them. Then under [clears throat] the film are the orders.
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They end in verales. There aren't any orders shown here. And then the last three are the more familiar that we'll use more in this course. We have families which end in viray like felo veririday or the felo virus family. Then
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we have a genus which ends in virus like ebola virus. And then a species like [clears throat] zire ebola virus. And so that's an ebola virus on the right there. A filamentous particle that causes hemorrhagic diseases. So we'll
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use family genus and species quite often in this course. But I want you to be aware of the bigger classification that viruses are put into. Why do we do this?
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We can see the relationships between different viruses and understand their evolution, which is something we will talk about.
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Now, in the old days, as as I mentioned, we used to discover viruses because we were interested in what was causing disease. So, we found yellow fever, we look for the virus smallox, we look for the virus polio virus, etc. But nowadays
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we still do that when a new virus disease when a new disease emerges we try and associate a virus with it. But more often we try to just discover everything that's out there. We want to find all the viruses that exist not just
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in living things but in inanimate objects as well. And this is an example of a a very nice study that was uh published not too long ago where they used uh artificial intelligence to find what they called the hidden RNA virus
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sphere. So they're very large databases of sequence data that you can access. So people will get water and sequence all the viruses in and then put it in a database and you can exploit that. You can probe it in ways that you wish. So
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what they did in this study, they took metat transanscripttos which again are RNA sequences from many environments and they translated them into proteins and asked the program to look for a specific fold in a protein an enzyme called RNA RNA
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polymerase. So RNA dependent RNA pulymerase is unique to RNA viruses and has a signature fold that's entirely conserved among all the RNA viruses. So they asked AI to find this fold and they found new species based on just looking
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for that as opposed to just looking for homology among the nucleotide species. So here u there were this this this uh picture shows you the established virus sphere at the time there were 21 supergroups those are shown in gray uh
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and then the expanded virusphere which they got from this study and then the hidden virusphere which they got that's in orange by probing for the fold in the RNA ply. So they got in all 161,000 new RNA species identified by doing this.
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And so you know the the limit is your creativity and your cleverness because there's so much data out there to be manipulated.
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So why do we care about any of this? Let me give you some reasons. First of all, viruses outnumber cellular life uh by 10 to one. more biodiversity in the vyrosphere. By by the way, when I say vyrosphere, I mean all the viruses
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on the planet. More biodiversity, more genetic diversity there than anywhere else. They drive biogeeochemical cycles as I briefly mentioned to you. They shape host populations and vice versa.
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Many of them are probably beneficial and obviously they're sources of new pathogens. So all these viruses out there can at some point get into humans and cause problems. That's what we saw with SARS KV2. A virus that existed in
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bats somehow made its way into humans and caused the pandemic. And so that's why we want to know uh what's out there that and all these other reasons. Now, I've told you today that there are lots of viruses out there, but actually we
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can simplify it and make themes that will make it easier for you to understand uh the diversity of viruses.
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And there are two things we can use. First, all genomes are parasites that need to function in a host cell, right?
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So, every virus genome needs to get into a host cell in order for it to reproduce. And more importantly, all virus genomes have to make messenger RNA that is translated by host ribosomes. So they're really parasites of the protein
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synthesis machinery because no virus genome encodes a protein synthesis system. It always has to use the host.
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It may tweak it by adding some tRNAs, for example, but no virus encodes everything you need to translate. So, a virus needs to make mRNA that can be translated by the host. So, next time we're going to use these two to try and
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put some order in the world of viruses. All right, see you next week. [music]
Topics:virologyvirusesviromebacteriophagesHIVherpesviruseswhale virusesocean virusesviral evolutionmicrobiology
