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Virology Lectures 2020 #1: What is a Virus?

Mar 27, 2020
good afternoon, welcome to viral adji. I am Vincent rockin yellow and I will be your teacher throughout this course. I am a professor at the Faculty of Medicine. I've had a lab there for 38 years working with

virus

es and I think they are. The coolest things on the planet are cooler than anything else out there, and part of my goal is to convince you that they're really cool. I love

virus

es. I have a passion for them that few people have and I want to pass on some of that. You now as a professor outside of the medical school I have no teaching obligations.
virology lectures 2020 1 what is a virus
I don't have to teach this course. I've been doing this for 10 years because I want you here on this campus to know about viruses when I started doing this. 10 years ago there was no

virology

course at Morningside and I thought you guys were paying $60k a year and not learning about viruses. This is completely unacceptable, so that is my motivation and I guarantee you that you will really like this course. You're going to like

what

you learn, it's not easy, but in the end you will know more about viruses than most people in the world and this is a good time to take this course because, as you know, we have a completely new virus. emerging from China and circulating around the world, and everything you've heard about it on Twitter and Facebook, etc., is probably wrong, but by the end of this course you'll get the facts and understand exactly

what

it is. going through this is what I feel if you want to understand life if you want to understand human health and disease you need to know about viruses we live and thrive in a literal cloud of viruses viruses infect every living being on the planet everything nothing escapes infection by viruses we regularly eat and breathe billions of virus particles, probably daily, and viral genomes are also part of our genome, they are really ubiquitous, they are everywhere and what is really remarkable is the spread of viruses in the planet and here is an example in the waters of the planet, just the oceans, salt water, there are more than 10 to 30 bacteria phages, these are viruses that infect 10 to 30 bacteria, that is too big for you to really understand, so let me give you two. forms for you first and a teaspoon of seawater there are a couple of million virus particles, so the next time you go swimming in the ocean and spit water at your friend, you will be aerosolizing the virus, it is completely harmless , but your virus is there. a bacteriophage particle weighs about a femp 2 grams so if we multiply that by 10 to 30 we get more biomass times a thousand times more than old elephants on earth so now you're starting to see how many particles there are and then if we put them End to end, each of those particles from 10 to 30 reach a hundred million light years in space, which is farther than the nearest galaxy, well beyond our solar system, of course, a distance incredibly fluid and these are things you can't even see, that's the amazing part.
virology lectures 2020 1 what is a virus

More Interesting Facts About,

virology lectures 2020 1 what is a virus...

There are many of them and this is just in the oceans and in this course we are going to talk a little about the impact of those viruses on the oceans and on global biogeochemistry. They have huge roles to play, so numbers are part of how viruses succeed. Whales, for example, are infected with members of a family of viruses called calluses, these are members, they are related to viruses that can cause gastroenteritis, we'll talk about that later in the course, gas, our itis is vomiting and diarrhea. we've all had it these are some commonly causing viruses that can also infect whales can cause rashes and blisters and also gastroenteritis not only in whales but also other marine mammals some of these whale viruses we think can infect humans and they spread from animals to humans, that's a word I'm going to use a lot in this course and these whales excrete 10 to 13 virus particles a day in their feces, a lot of virus particles go into the ocean, there's a lot of whales there. out and the whales aren't the only ones, in fact this is just another example of the viral numbers game so to speak, and that is a particle of the Khaleesi virus in its glorious color, of course these viruses are not colored at all , we color them because it looks good in their information, but like you.
virology lectures 2020 1 what is a virus
We will see later, we know many very detailed structures of virus particles that we can use to understand how they work. It's a little bit more about the oceans. Here is a set of pie charts showing the number of viruses in relation to protists and prokaryotes etc. On the left we have biomass and you can see that the yellow ones are the prokaryotes, bacteria largely make up most of the biomass in the ocean, there is a lot of microbial activity in the ocean, in fact, it represents most of the oxygen that we breathe. Photosynthetic bacteria in the oceans and viruses in blue are only a very small part of the biomass.
virology lectures 2020 1 what is a virus
However, if we now look at the number of particles on the right or the abundance, viruses make up 94 percent of the particles in the ocean if we only count one bacteria and one. viruses like one each now viruses win the race, they are more abundant in particles than anything else and these viruses are not just bad news, someone said years ago that a virus is a bit of bad news wrapped in a protein. I think sometimes that's completely wrong. may be, but as we will see later in the oceans, these viruses are responsible for recycling a lot of organic matter to make it available, so they have a big role to play and I just want to point out again in a leader of coastal communities .
In the water, there are more virus particles than there are people on Earth and, as you will see, they have the greatest genetic diversity on the planet. Nothing comes close to having the number of genes in total. Viruses have another sobering number. Right now, today there are about ten to sixteenth genomes of the HIV human immunodeficiency virus on the planet is also a huge number and we know this because we know how many people are infected, about 37 million currently, we know how many genomes they usually have, so we can do the math. very easily, but what does the number really mean?
It means that of all the drugs we have to treat HIV we have more than 40 and they are very effective and now if you are infected with the virus you can live a life without getting diseases due to these drugs, however, within these ten genomes By the sixteenth there is already resistance to all of them because, as you will see, mutations arise randomly and, therefore, no matter how many drugs we make against this particular virus, there will always be resistance and that is a problem that we will talk about when we talk about AIDS. How many of you now have a virus infection? raise your hand.
I guess they don't want to identify themselves properly. I understand it, but everyone knows it. They are all infected. I don't want to point fingers at anyone. I am infected. In fact, we all currently have about a dozen different herpes viruses, including herpes simplex, one in two, varicella-zoster virus, chickenpox virus, although if you're vaccinated, you may have avoided that cytomegalovirus Epstein. -barr virus and then other herpes viruses six, seven and eight serology studies have shown that the US over 90% of the population has these viruses and once you get them you can't get rid of them. I like to say that unlike love, herpes is forever, it's true and we'll talk about why they stay with you and why you can't.
I ever get rid of them, I have to say that I have an Instagram account where I put photos of viruses and so on, and I regularly receive notices from people who say that my herpes was cured by doctor so-and-so, let me tell you his number, it is wrong, you can't cure herpes and you will learn why at the herpes conference, so each of us has at least a dozen herpes viruses, but we also have many more, let me tell you that you know we have a microbiome in each part. Of you have certain bacteria associated with your skin your eyes our respiratory tract gastrointestinal everywhere there is a different collection of bacteria that are good, they are beneficial, we are just starting to learn why, but there are also viruses in every part of your body that have. a viral and on the left our pie chart showing RNA and DNA viruses and different organ systems, nervous system, respiratory system, you are a genital tract, etc., even in health, we have viruses in all these places, all of us if you did a survey of all of you.
I would find viruses like this and on you, but you're fine and that's the interesting part. We believe they are beneficial. We have some evidence of this that we will cover in this course. We are currently looking for viruses everywhere and I want to. play this movie on the left, now we can access anything on the planet to look for viruses and there I will show you how to access the whale breath virus. What they have done here is that they have created a drone that is piloted by the people on the boat and when it passes over the whales a small dish opens and collects the whale's breath.
I don't know if you can grasp that it's quite fast, that little dish that appears is like a Petri dish. opens, the whale breath comes in once again and they can collect it, they can bring it back to the lab, sequence it and find out how many viruses are in the whale breath. Isn't that something you wanted to know? Could you use it? that at a party you said that you know how many viruses there are in whales' breath, there are many, so we can take samples from any part of the planet and we would like to know what there is just a few weeks ago I saw a newspaper where they went up to a glacier in the western part of China and they dug very deep and took out the ice cores, brought them back to the lab and thawed them and found viruses and these ice cores are 15,000 years old, so we can really understand what is happening. the planet when doing this type of sampling is quite remarkable.
I mentioned at the beginning that we have viral genomes as part of our DNA and that is illustrated here in this pie chart, as you know, our genome is 3.2 billion bases long, the sequence from many years ago. and many genomes are being sequenced right now because the cost has dropped substantially. The coding genes are very small, as you can see here, only one and a half percent, and there are many other sequences that do other things, but I want to point you to this 8.3 percent. which is labeled as LTR retrotransposons. I'll talk about exactly what they are in a later lecture, but essentially a good fraction of these are remnants of retrovirus infections that occurred long before we were Homo sapiens and happened to our ancestors. and they were transmitted to us and, in fact, some of the genes of those retroviruses have been co-opted throughout evolution so that they now have uses in us.
Some of these protein-coding genes come from retrovirus infections. In fact, there are virus sequences scattered around. throughout our genome that aren't shown here and we're wondering what effects they have, whether they're useful, and if so, what they're doing and people are starting to get interesting results about that over the years, as you'll see. , most of the work on viruses and most The discovery of viruses is driven by disease and that is illustrated in this graph that shows the causes of global deaths in 2017 and you can see the main cardiovascular diseases, almost 18 million deaths around the world in a year and I have put arrows next to some of the places where viruses are participating here, the clearest being HIV, the causative agent of AIDS, of course, almost a million deaths in 2017, but there are other viruses that may not be obvious to you, for example a lot of hepatitis is viral so it is at the top.
We list many diarrheal diseases that are also viral respiratory diseases and so this drives a lot of research into viruses, but we increasingly understand the role that viruses play in ecosystems and in beneficial functions for the planet, so La Research is expanding beyond the simple cause of the disease, but surprisingly, despite having all these viruses around us, you have so many inside you and around you the air is full of them right now. Are you OK. You rarely get sick. You get a cold from time to time. maybe you have gastroenteritis, if you are healthy you don't get sick, so why?
Let's explore why we don't get infected with all these viruses and the first reason is that most of them just pass through us and here is a result. from a study of supermarkets in Washington DC where they bought cabbage and took it to the lab and looked for viruses and found that each serving of cabbage would have between ten and eight particles of this particular virus, it's an insect virus that infects this. the caterpillar is called a cabbage looper so if you ever eat coleslaw this virus will be on it, if you eat cabbage and even if you cook it the virus will probably still be inactive but you will still be ingesting it but they can't infect us.
Then they pass throughus, so many of the viruses we encounter cannot reproduce in our cells, so they pass through them. The same goes for the viruses we inhale that land on our skin at the bottom. It's a different study where they looked at viruses. RNA sequences in human feces can easily do this. You can collect feces in sequence. The most common RNA virus is called pepper mild model virus. It's in ninety percent of the samples, which is why most people apparently eat peppers. I didn't know. This is a pepper that is infected with the virus, of course if you saw that in a supermarket you probably wouldn't buy it, but they can also be infected without showing symptoms and you eat them and these viruses pass through you, they don't infect you and I get Send emails emails quite regularly because now you can test your viral stool.
Did you know who is a company that will do that for you? I get an email saying "OMG I have this pepper virus, what am I going to do?" Then I see a doctor and he says no. You don't have to see anyone because these viruses don't replicate, nothing I see is really pathogenic, so one reason is that they don't replicate in this amount of viruses that are good. I call them beneficial viruses and I have three examples for you. On the left is a herb that lives around hot springs in places like Yellowstone National Park.
I've been to any of those where you see hot water coming out from where it's heated deep in the ground and around it there are grasses that are growing, they're thermo-tolerant grasses. Here is one of them, I can't helium lannigan, OSEM can grow. at 55 degrees Celsius you can take this herb to the lab and grow it at 55 degrees and several years ago people discovered that this herb is infected with a fungus this fungus here are all the little wavy lines from the Kerrville area if you take the fungus Then you plant They can no longer grow due to high temperatures so somehow the fungus confers thermotolerance but it's even more complicated inside the fungus there is a virus that infects the fungus and if you only have the fungus without the virus on the planet.
It does not confer thermal tolerance, so the virus helps is a 3-way mutualism plant fungal virus that allows the plant to grow and the others, of course, to get a place to live. Another very good one on the right. I don't know if you've heard it. of parasitoid wasps, these are wasps that lay their eggs in caterpillars and then the eggs hatch and the new wasps eat the caterpillar and explode, it's like an alien basically, but this is real life and what these wasps do when they lay their eggs. injects the virus along with the egg, it is called virus paladin and that virus is encoded in the genome of the wasp, the wasp, you know, man encodes the viral genes that form the protein coat of the virus and then this virus does not replicates in the caterpillar all it does is produce proteins that immunosuppress the caterpillar so it doesn't reject the wasp eggs and larvae, that's why the virus is placed along with the wasp eggs, so of course this virus is good for the wasp, it is not. good for the caterpillar obviously, but neither is the wasp, but another example of a beneficial arrangement and these are just two tons of examples in the entire living world where we can see viruses involved in these types of interactions and they are beneficial in some way to at least one of the hosts can now ask if this happens in mammals because it happened in us, we don't know if it happens in us, if our viruses are beneficial or not, because we can't experiment on us properly, weakly, we can't do experiments. but one day there will be broad-acting antivirals, like broad-acting antimicrobials for bacteria, and we'll give them to people under certain conditions and we'll kill off most of their viruses and we'll be able to see if it's bad or not, but in the meantime we won't. we know that, but we do know that in mice the answer seems to be yes, so here's an experiment where they grew bacteria-free mice, germ-free mice, that's gf and here they're conventional.
I swear his intestines are full of bacteria. the normal microbiome, so on the right is a section of the small intestine. You can see the villi here. Conventional mice, so they grew up with a normal gut microbiome. Nice villi and then at the bottom they were stained for protein C d3, which is a marker. of lymphocytes T lymphocytes and you can see that there are some lymphocytes here now if you do the same with the mice cultured without bacteria, the villi are in bad condition, you can see that their morphology is incorrect and there are no longer many lymphocytes in these areas, okay ?
A microbiome is needed for proper development and for proper development of the immune system. The mouse in the middle was infected with a mouse norovirus which is mouse norovirus mnv and you can see that part of the abnormality has been restored not completely, but it is a little better. than the germ-free ones, but some of the lymphocytes have also returned, so apparently this virus is restoring whatever function the microbiome has provided, so these are very tempting experiments, there is a lot to do, but they suggest that viruses at least in a mammal it can have a beneficial role.
The other reason most of you are fine is that you have a really good immune system that works most of the time and most of these viruses that you inhale, if they manage to grow on you, they won't. because your immune system will take care of it now if it happens that if your immune system is down let's say you are immunosuppressed if you have an organ transplant if you have AIDS you will be immunosuppressed even measles will make you immunosuppressed then the simplest viral infection can be lethal which points out the importance of the immune system and preventing viruses from growing in us, so those are some of the reasons why you can be healthy with all these viruses around you.
Here is another interesting example I want to give. again, it's a virus that infects almost everyone on the planet, it's a polyomavirus that shows up there in the middle and this is interesting, it infects us pretty early in life, we usually get it from our family members, it spreads to through respiratory secretions, saliva aerosols produced when speaking, etc. and you get infected then you are infected for life and if you are healthy you normally have no symptoms if you are immunocompromised at some point in your life you can develop serious illness but these viruses can be routinely shed in respiratory secretions and in urine as well and some people secrete hundreds of thousands of particles per ml in urine, so I always like to remind you that when you go to a public bathroom, you know that every time the toilet is flushed, an aerosol is created.
I don't want them to find out. paranoid but it is likely that that aerosol has the viral virus from the person who was just before you and maybe at the end of this course someone told me this a couple of years ago I no longer went out or ate anything because I was paranoid, I hope everyone Anyway, these polyomaviruses don't end up the same way because they spread within families that you may be used to studying human migration and that's what this map is, so the dotted line is the progress of Homo sapiens since Africa towards Europe and Asia and the Americas determined by the genome sequence the black lines are the migration of Homo sapiens according to infections with this virus, we can distinguish different lineages because each one has a unique polyomavirus, as I said, it tends to spread in families , so the movement of families can be tracked.
By looking at what they have been infected with, it can be seen that it mimics the Out of Africa movement and even provides more details about the migration of humans than the genome. Again, it is a harmless virus and is useful for tracking where people are. They've moved, so this is just a small hint of what's to come. We are going to delve into all of these topics in great detail in this course. Viruses are amazing. It really is an extraordinary topic. Once, one year, a student wrote that after finishing the course. At every conference he had something to tell his roommate that he didn't know and I think you'll find the same thing this year too.
It is a remarkable topic and I want to emphasize that it is an integrative science. What do I mean? To understand biology you need to understand not only viruses, but also chemistry, biochemistry, cell biology, physiology, if you want to understand how viruses spread, you need to know a little bit of sociology, certainly epidemiology, you need to know many topics and, in the process of learning about viruses. Here you will learn many auxiliary things. Several students have told me in the past that studying viruses makes biology make sense and that is because it is integrative, it really brings a lot of things together and these are my goals for the course.
I want to give you a general idea that the way this course is organized is not because of viruses. If you attend many colleges and universities in the US, you will find

virology

courses, some of them mimic this, but others teach by virus. have a lecture on influenza, a lecture on herpes, a lecture on retroviruses, that's the wrong way to teach an introductory biology course, you won't learn any principles that way, all you'll know is a collection of facts about different virus which is great for a more advanced course, but for an introductory course you need to know the principles and that's what I'm going to teach you if you notice that the syllabus for each lesson is for the first 13 lessons or so, it's a step in the replication cycle of a virus we'll look at it slowly and then in the second half of the course we'll explore how viruses cause disease and we have a cast of viruses that we'll come back to all the time so you don't have to learn every virus, but In the end you'll have a great overview of how viruses work, so that's what I'm talking about.
I want to teach it to you as an integrative discipline, not as a collection of viruses, diseases or genes, and as I said before, We are going to learn things that will surprise the uninformed and the informed and scare the uninformed. There is a lot of fear right now about this new coronavirus due to lack of information. Now I'll show you how to get that information at the end. and I guarantee you that in two or three years, when another outbreak occurs, you will look back on this course and say now I understand what is happening because of what we were taught and, like I said, we are in a perfect time now because I have a new virus circulating and Just this morning I pulled out these headlines to show you what I'm going to teach you to be able to do here at the top, you know, you don't go to Wuhan, you don't leave Wuhan eager.
Of course, it originated in a fish market in Wuhan and the virus could mutate and spread further. Well, here's another article. China warns that the virus could mutate and spread. Where did all this come from? It came from the Vice Minister of the National Health Commission. There is a possibility of a viral mutation. What you are going to learn in this course is that this is wrong, there is no possibility of mutation of the virus, it is already happening, viruses mutate with each reproduction cycle, that corona virus has already mutated widely as it passes from person to person. another, what they mean, of course. is that eventually it will have a mutation that will sort of make it spread more, but the distinction is subtle and the Minister of Health doesn't know it and then the press just picks it up and amplifies it and that's what you see and so on every outbreak I see their headlines like this the virus can mutate and from year to year it seems that they do not learn the fundamentals but you will learn in this course you will understand why this statement is incorrect and what kind of consequences that mutation could have for viruses in a population human.
I guarantee that when you see these headlines in five years you will understand why they are not correct. One of the things I'm going to do in this course is have quizzes as we talk here to give you some breathing space so you can do this on a laptop, a cell phone, a tablet, whatever you have connected to the Internet, you need to go to Socrative and that's the link there, socrative.com, log in as a student and you will be asked to log in to the room. The name is virus. What else could be correct?
And here's our first quiz just to make sure it works. This is the statement that is true. Hey, all viruses make us sick and can be lethal if our immune system can control them. most viral infections see humans are usually infected with one virus at a time D the press is generally right in their virology reports and E our immune system cannot handle most infections which is true this is not recorded in no way does your grade count it's just to make sure you're understanding it some of them are easy and you'll get some that you won't get and then I'll explain it to you it's a good way to teach you the material and at some point in the near future You will get one hundred percent, but it will take a few

lectures

before that happens, at least that has been my experience.
How did we do it? Yeah come onto be saints. You already have one hundred percent. That never happened. You must be exceptional. Yes, our museum. can control most infections, that's the answer, that's a good sign for the rest of the course, so I'll do it periodically at 3, 3, 4 per lecture just to make sure you're doing it right, so now let's define a virus that I am going to need this definition for the rest of the course what is a virus I have to tell you that every year I change this it is difficult for me to include what we have learned and the first definition from 10 years ago that I gave is different from this one and the definition of This year it is an infectious obligate intracellular parasite comprising genetic material which may be DNA or RNA often surrounded by a protein coat and sometimes a membrane.
It's a bit of a weak definition, there's a lot of qualifications there, but that's what it is, let's break it down, it's so infectious. In fact, I debated removing it from the definition this year, but I think it's the important concept: infectious means that the virus can move from one host to another and from one cell to another and enter the host because an obligate intracellular parasite means virus. they have to enter cells in order to reproduce they will not reproduce in the air or on the skin they have to enter a cell so infectious they move from one cell to another cell host or obligate host they have to enter the cell now the parasite is something that takes something from another organism and harms it, so taking nutrients is considered harmful because otherwise you would have those nutrients and you will see many ways that viruses harm their hosts and you may feel confused at some point we are going to speak.
Viruses that infect us without harming us, how can that happen? But they are still taking something because in order to produce more virus particles they have to take something from the host, so it may not be serious or openly damage the DNA or RNA. Viruses are unique and their genome may always be the same for a particular type of virus, so the influenza virus has always had RNA genomes and herpes viruses always have DNA genomes, but nowhere else in the biological world do we see RNA being genome and that is very interesting and we're going to talk about that when we talk about where viruses came from that were often surrounded by a protein coat, well it turns out that the vast majority of viruses have a protein coat.
I added this this year because I want to include as viruses some naked nucleic acid molecules like this one here. It is a piece of RNA called a viroid and it infects plants. It has to get inside the plant cells, it reproduces and moves inside the plant and can cause plant diseases. They called me viroid because people didn't think they were viruses because they didn't have a capsid, the protein coat. I don't think that should be the defining character of a virus. I want to include viroids in viruses, that's why I have them. In fact, they're often surrounded, as you can see in the diagrams here, most of these viruses have a protein coat, so here at the bottom left, this icosahedron particle which is the poliovirus, next to it is the adenovirus.
These are made of pure protein shells with the nucleic acid inside. We'll learn more about this as we go, other viruses sometimes have a membrane so here's a corona virus that has a lipid membrane around it which doesn't aggregate and polio viruses don't so not all Viruses have a membrane and many here do, that's an option, but most of them will have some kind of protein code around the nucleic acid, except for these fibroids, and we'll talk about viroids and other naked nucleic acid viral particles more forward. Now viruses have to infect cells in order to reproduce, if they don't they disappear and I'm sure many lineages of viruses have disappeared over the billions of years they've been around, they can't find a host and that's the end, But when we study viruses we also have to study the host cell so that each solution of the virus's reproductive cycle reveals something about the host.
Many of the great discoveries about host cells were found using virus-infected cells and I will point them out to you as we go along and these are some, of course, various hosts for viruses, as I said, they infect everything on the planet. Do you think there is only one organism? Well, there are so many species out there that you can't expect to find a virus for each one because no one studies them, right? I always learned that there are more insects in certain areas than we have ever catalogued, but the only organism I don't know a virus for is tetrahymena, but I bet there is one and they just haven't found it for many years C elegans there were no viruses from C elegans and then they were found so you just have to look hard enough to be able to study the virus of any organism and learn about the organism as well so that mosquitoes can infect us of course this is a very interesting protist that lives in the ocean is one of the most numerous protists in the ocean and there is a virus that infects it which we will talk about and these are tulips these are tulips that are very appreciated in Holland they have stripes and the stripes are caused by a viral infection and people used to breed these tulips to make the stripes and without knowing it they included the virus because the virus is what interrupts the pigmentation and makes them attack, so the other question is that our virus is alive and I have a poll on my blog here, which I just saw the other day, about 7,000 people have taken it and you can see it's pretty evenly split between yes and no and something in between, I don't know what it would be, are you living or not and So I've thought about this a lot and I have an answer to this question and it is not a simple answer, it is captured on this slide, so when they urinate, most people think of viruses, they think of a particle like the one on the left in polyomavirus. and that is in no way a form of living being, it is a protein show with some nucleic acid, if it is here on the table it will stay there forever and do nothing that it can't reproduce on its own, so it just can't be.
Alive has the ability to become alive when it enters a cell, kind of like a spore when you pour water on it, but a spore has a lot of different energy production systems etc. that viruses don't have, so I don't think so. that's a good analogy, so the virus particle that I call a virion, the infectious virus particle is not alive, it can't be, but when the virus infects a cell, the infected cell is absorbed by the virus and now goes about its business. produce virus particles, it does not. It is no longer just a cell, it is a cell infected with a virus and it is alive, so I see it this way: a virus is an organism with two phases, one that is not alive, which is the particle and another which is the infected cell.
I think that solves the problem. but people generally don't like to separate solutions like this, so it doesn't really take hold, but it has to because they are infected cells, they certainly live in the particle, it can't be that the problem is us, as I say when the people think. Viruses always think about the particle and not the infected cell, so that's my answer. The other thing I want to warn you here at the beginning of this course is to please don't anthropomorphize viruses, it's very easy to do because it makes it easier. to talk about them and if you read any articles in the popular press about viruses, they will have viruses doing things the virus wants to do this or the goal of the virus is to do this, they have no goal, they don't believe that they don't. employ they don't ensure exhibition exhibition you know how to do anything they are completely passive agents and you can think well so what I understand is that why I can't say it anyway is because if you anthropomorphize then you are going to misinterpret the things that happen to you.
We will be given targets for viruses when in reality we are not and it is very important to look at all the things that we are going to look at in terms of virology here with a neutral attitude, understanding that these things happen at random, mutations happen to random lists. in a genome and can lead to something, but viruses are not intended to infect people and make them sick. The only selective force for a virus is to find a new host, which is the main selective force. It is a completely passive force and no matter what happens during evolution to make the selected effective, so try not to do this.
I try not to anthropomorphize, it's also very difficult with science writers who do it often because it's very easy and the alternative is sometimes complicated, but it's actually a warning not to do it. Think that way, don't think that viruses can actively do things, they are passive now. The other part of the definition of viruses that I used to use was that they were very small, in fact, I gave them a limit, I said they would pass. through a point to micron filter, there is no more size in the definition of viruses because now we have viruses that are much larger than 0.2 microns, we have one and a half micron viruses and everything in between, so size is no longer part of the definition. but I want to give you an idea of ​​the size of the virus.
They are very small here. Here's a hundred thousand X E. coli and there's a bacteriophage virus attached to it, so you can see it's a lot smaller than the E. coli, but you know. not enormously smaller here in panel D is the HIV particle and that rod-shaped virus is the plant virus tobacco mosaic virus which we'll talk about in a moment, so they're relatively large compared to E. coli and then that little panel has a variety of objects that are magnified up to a million times here and here we have a carbon atom, we have a tRNA and an antibody molecule, there is a ribosome and some other cellular components, actin and myosin, etc., and here's a poliovirus particle, so it's about the size of a ribosome and so on, in this panel it's quite small compared to E coli and that's not the smallest particle, so they get there 30 nanometers, but there are viruses between 20 and 30 nanometers in diameter, those are the smallest we know, so here is the other way.
Looking at the size range of virus particles first, at the bottom there is a cell with its nucleus and various organelles, a eukaryotic cell of course, and here are some virus particles outside of it and we have blown them up to the right and in the largest. is a herpes virus about 200 nanometers in diameter, making it one of the largest, and there is also a poliovirus the size of ribosomes, so small compared to a cell that many of these virus particles could fit inside a cell at the top, it's an interesting scale that goes from the plant cells on the left to the atoms all the way on the right and how you would visualize each of these entities invites you to see viruses somewhere in between between the bacteria and some of the smaller components and you cannot normally see the viruses for With the light microscope you can see some.
I'm going to show you one in a moment, but mostly you need to use electron microscopy to see viruses, and of course everything is smaller than that. You also need to use these types of techniques. These are the answers. the question is how many viruses could you put on the head of a pin in case you are interested there is a pin head that has a dust mite there that little pink thing is a dust mite and in the square here there are a variety of very small objects including some red blood cells one of these is a lymphocyte one of these is a yeast and here we have some bacteria so you can just barely see this long structure which is a virus, the Ebola virus, it turns out it's very long so you can see it here . it's very small relative to the pin itself, the pin is about 2000 microns in diameter, so you could put 500 million rhinoviruses on the head of a pin, those are the viruses that cause the common cold and if you have a common cold , every time you speak you are making an aerosol and those droplets are full of enough rhinoviruses to infect many people and that is part of the strategy for the viruses to transmit, produce many progeny and pass from one host to another.
Now we used to think that viruses were smaller than the two micron point. I'm going to tell you why in a moment and some of the smallest viruses that we knew about the Rhino virus say it's about the same size as polio, it's about 30 nanometers, HIV is a little bit bigger and the herpes virus is a little bigger than HIV, as I showed you, but about 15 years ago a group of viruses was discovered that we could now call giant viruses because they were bigger than anything we had ever seen and one of them is the Mimi virus which shown here on the cover of an American scientist and you can see that it is quite a bit larger. than any virus we knew here is an electron micrograph of a cell infected with Mimi virus particles.
We'll talk a little bit about giant viruses and what they mean, but they've expanded the size range and now we have even bigger viruses. one is the largest one I know of on the left and it is a light micrograph of this virus. HePandora virus simply put it under the microscope in the laboratory. They are too one and a half microns long for me to see them with the light microscope. quote the Pandora virus, which is the largest virus we know and the genome has 2 and a half million base pairs of DNA huge, they mostly encode genes that we have never seen before and the more viruses we discover, this is incredible, the more viruses we find, the more genes we find.
Find out whose features we have never seen before. The proteins are nothing like the proteins we know, so it's a very exciting time to discover viruses because all kinds of new things can be found. There is also a fundamental difference between viruses and bacteria. and the way they reproduce and bacteria is shown on the bottom right here, you take a single bacteria, you put it in a broth, it starts to divide, it forms two, four and eight, binary fission. If you put a virus in a broth, it won't do anything. it needs a cell and it will go into the cell but it won't divide, it will make parts, it will make genomes and capsid parts and it will assemble them and then it will have an infectious particle, a fundamentally different way of reproducing, it will make the parts assemble the final product and as Consequently, you add viruses to the cells, you have a period where nothing seems to happen, no infectious virus is generated, we call it Eclipse and then at some point after infection it varies depending on the virus, then you see new particles infectious created, so fundamental difference between viruses and bacteria, so let's take a moment to ask which of the following statements is true regarding bacterial versus viral replication.
Viruses must be assembled using preformed components. Bacteria do not replicate through binary fission like viruses do. The bacteria must be assembled using preformed components. The virus. It doesn't have an eclipse period and viruses replicate via binary fission, okay, how do we do it? Yes, viruses must be assembled using preformed components. 91% of you understood that some of you got the others, but that's the key. Everything else is wrong but bacteria replicate via binary fission but therefore C is also wrong viruses have an eclipse period they do not replicate via binary fission how old are they? We can now sequence many viral genomes and do computational biology experiments to estimate the evolutionary rates of the oldest genome that What I know so far in the literature is a retrovirus that appears to have existed 450 million years ago in the Ordovician period, which would be right here where the first land plants are emerging and it seems to originate in the oceans, which is kind of interesting. because there they had the first animals, fish, that grew or evolved and then came to land, so maybe the virus evolved in the ocean and came to land, and this is one of the interesting creatures that lived then, Ortho Sarris lived 488 million years ago.
It is difficult to go further because the mutation rates of the genome of viruses are so high that the data decays beyond a certain age and, of course, we have no fossils from which we can extract nucleic acids. Nucleic acids do not last long in fossils, so they are very difficult to obtain. some ancient fossils, but not millions and billions of years old. I believe that viruses originated before cells, which would be many billions of years ago. I think the first viruses were actually self-replicating nucleic acids that could replicate outside of cells. Self-polymerizing nucleic acids. This is one of the ideas for the origin of life, we call those replicas, they are replicating nucleic acids, they are essentially viruses and from those cells they emerged and then the viruses said, well, they didn't say, of course, that the virus has entered the cells.
Because that was a hospitable place, we will talk more about that when we talk about evolution now. If you start going through recorded history, you start to see evidence of viral infection. We didn't know what viruses were until around the end of the 19th century. but here on the left a Vaz from 700 BC. where it says Hector rabid referring to the rabies virus presumably or rabies the disease and on the right and an Egyptian engraving from these years 1580 BC. where this young man has a foot that looks exactly like what polio myelitis is. today we call it drop foot, the muscles are paralyzed so you can't keep your foot elevated it just falls, we don't really know if this is folio but it looks very similar and there are many references in history over the years that suggest Virus infections existed in the 11th century.
We know that variolation was practiced in China. Now, at this time, smallpox was devastating human civilizations. This was a virus that likely evolved from camels and rodents to infect humans as human populations grew. These viruses invaded them. and smallpox was particularly devastating it killed a lot of people in China they practice a type of vaccination and this is in the historical record where people with smallpox would take the pustules, crush them and blow them into someone's nose so they wouldn't get infected. The disease had no idea this was a virus, of course, but they just knew that some people who survived smallpox never got it again, so they said, "We'll give it to them," and about a third of the people died, but the other two thirds do not.
Vaccine approved by the FDA, but they did it and then the wife of the English ambassador to Turkey the practice had come to Turkey and she realized this and brought it back to England and they started practicing the variation and then in the decade In the 1790s, Edward Jenner did experiments to establish vaccination, which we'll talk about later in the vaccine conference, but let's talk now about the origin of this virus concept, how it grew from a point where we didn't know anything about any microbe to where now we have this concept of a virus. We started with yeast in the 1600s, he invented the microscope and for the first time we saw that there were living things that couldn't be seen because people thought that everything I can see, that's all there is in the world. but he said: Oh, in the water there are little things swimming around the concept of microbes.
Pasteur of course went further and showed that microbes can do good things, in particular bacteria can make wine and cheese etc., and at that point we know that there are bacteria exist as microscopic organisms that can do these things and then finally coke. Towards the end of the 19th century it was said that these bacteria can cause disease, so we established the germ theory of microbiology, so by the end of the 19th century we know about bacteria and we know what they are. we can do and we know that they cause diseases, but we know nothing about viruses, still a key point here is that we used the word virus long before this, we can find as early as 1728 the use of viruses and literature to describe any agent that causes an infection, so in 1728 we don't know about bacteria, but we know that people can transmit a disease to each other and people started saying, well, this is a virus that is doing this because virus is a Latin name for poison. , so They thought that a poison was spreading from one person to another.
They thought it was some kind of liquid that could spread in the air. When Pastor came on the scene, he decided that every virus is a microbe. Remember he was studying bacteria and he said these bacteria or viruses, they're all the same these things that make people sick, they're viruses, so again, we don't know what a virus is yet, but we're using the name virus to explain infectious diseases caused by by bacteria. It's a little confusing, but keep in mind. with me he discovered that this gentleman Chamberland was working with Pasteur and the water they had in the laboratory was dirty, it was contaminated, so he designed a filter to clean it, it is called a Chamberlain filter, it has a porcelain insert and you put water in it. and you try a suction, the water goes through the bacteria is retained in the filter so it can produce clean water and he ended up selling this in Paris.
They could have clean water. Chamberlain filter. Pasteur used this in the laboratory and figured out whatever it was. that caused rabies, those who thought it was a bacteria passed through the filter, which then must be a small bacteria and the pores have a size of approximately 0.2 microns. Towards the end of the 19th century, by then people were smoking a lot of tobacco and in Germany. and in other parts of Europe there is a disease that affects backhoe crops, called tobacco mosaic disease, which makes the leaves turn red like this and affects the price of tobacco, so people want to know what is causing it , so a couple of scientists took the Chamberland filter and said it must be bacteria, so we ground up the leaves and filtered them, but what they found was that there was nothing stuck to the filter.
The disease agent entered the broth. Well, one of them said it's just a little bacteria, but the other scientist. he said no, this is something different and that's where the concept of a virus as a different entity emerged. They called these viruses filterable. Now remember that viruses are everything. They called them filterable viruses. These two individuals discovered tobacco mosaic disease. Filterable virus again. Viruses, that is, some kind of virus. liquid for many years people thought that viruses are actually liquid in 1898 the first animal virus was discovered foot and mouth disease a very important livestock virus that we deal with to this day and with the passage of time the key concept It wasn't just They're small, they passed through this 2 micron filter point, which we now know not all viruses do, but they won't replicate in a broth.
They need a cell to grow in, so if you take the filtrate and put it on a tobacco leaf, it will grow. but if you just incubate the filtrate on its own, the virus will not reproduce, but again at this point, 1898 we still think that viruses are liquid, many new viruses are discovered, yellow fever, rabies, smallpox, polio, etc., even Until 1933, we are not sure if these particles are liquid, but we still call them filterable viruses and here is a good graph of the discovery of bacteria and viruses. Now introduces efficient methods for working with bacteria. You see that the bacteria discovered increase and the number of viruses also increases.
Until 1935 we still called them filterable viruses, but a key experiment. They are actually two key experiments that change. The first is the development of the electron microscope by Helmut Ruska and Germany and that is the first e/m on the left. In 1939 he took a photograph of a virus infected with E. coli and saw these particles in it. These are bacteria phages. First image of a bacteria phage. For the first time we realize that the virus is not a liquid, it is a particle. Our next question is which one. The key concept first discovered about viruses that distinguishes them from other microorganisms too large to pass through a spot could a two-micron filter only replicate in broth make tobacco plants sick small enough to pass through a filter none of the above how do we make it small enough to pass through a filter, that's right, yes, so at this point they are not too big to pass through a filter, today they are, but back then the key point was that they don't They did it, they are not replicated in broth, of course, they need sales. in which replicating making tobacco plants sick is not a key characteristic another key experiment the same year as electron micrography 1939 people are making growth curves with bacteria and viruses remember you take it to your room you put it in broth and it starts to divide by binary fission, if you take a virus and infect cells, there is always a delay in this eclipse and they said it can't be a small bacteria because bacteria don't have this delay, it has to be something different, between e/m and this.
It was clear that a virus was something different from a bacteria, so they stopped calling them filterable viruses; now they were just viruses so we had viruses and bacteria that were disease agents so there's a bit of a complicated history there but I wanted you to know that our current understanding of a virus wasn't always like that and if you look in the literature and you see this in ancient times, they were talking about something else, today we know a lot of information about viruses, we take photographs of a variety of them using electron micrography here is a bacteriophage a particular type that has a beautiful tail and fibers of the cola tobacco mosaic virus the one that started all this the one that caused this disease the rabies virus and a virus that causes gastroenteritis we know great details about many viruses we can resolve their three-dimensional structures we cannot know where each atom is in the particle of the virus, these are two different visions of the poliovirus, one of the viruses that I have worked on for most of my career.
We know the chemical formula of the virus because we know how many atoms it has and on the left there is a three-dimensional structure of very highresolution where we can locate each atom in three dimensions and on the right the lowest resolution we will talk about how we get them later and what they mean. This is the virus that I carry on my cell phone, this is the poliovirus with its receptor and I know other people who have viruses on their phones but not that type. We classify viruses so that they make sense not because there is a natural organization but because humans Me I like to classify things and I often refer to classification throughout this course, so I want you to understand what I'm talking about.
Nowadays we classify viruses mainly by sequence, we sequence the genome and say, oh, it's this virus, this is how the new virus appears. China was identified from one of the patients, the isolated virus, they sequenced the entire genome, about 15,000 bases, they put it on a computer, they made a phylogenetic tree and boom, it is a corona virus similar to the SARS virus because you can see exactly on the tree, that's how we classify viruses and of course we get something new that we have never seen, we have nowhere to put it on the tree and it exists on its own until new relatives arrive in the old days we used to use other criteria like the shell, the membrane. the dimensions but we don't really use them for classification anymore we use the classic hierarchical system of classification that you have probably encountered in other organisms we start with orders in this course I will mainly talk about families of viruses with which they all end in viridi, for example, viruses of Ebola are part of the family phylo viridi or filovirus, then we go to the general, in this case, to the Ebola virus and then to the virus species, so I want you to understand when I say to feel a truth or a corner of your idioms that talk about the family level etc, the discovery of viruses is no longer driven by disease, of course when a disease occurs we would like to know if a virus was involved, but now a big part of biology is knowing what's out there and how it affects. ecosystems and here is a great experiment from a few years ago in which several research groups isolated 220 different species of invertebrates, all collected in China.
You can see various insects, crustaceans, worms, mollusks, etc., and they just crushed them and asked what virus. we found through sequencing a complete sequencing and in each of these organisms each of these species they found new viruses in the RNA viruses are in orange here at the top you can see many new RNA viruses in each of these and most of them are new things that we've never seen before, so this drives the discovery of viruses, now the ability to very quickly sequence many genomes and know what's out there now, which you can ask: why do we care about all these other things? why don't we just focus on the viruses that cause disease here are some reasons first of all I said before that viruses outnumber cellular life by at least ten to one they have the greatest biodiversity on the planet and we know that viruses They exchange genes not only with each other but also with their hosts, so that's important and we need to know that they drive global biogeochemical cycles.
This year we will be giving an ecology lecture for the first time to see how viruses interact with broader global ecosystems and see how they behave. as important for the recycling of many nutrients as I also mentioned, they can be beneficial, that is why we want to know what viruses exist. They are beneficial, for example, there are some recently discovered viruses that only infect insects and are now used as a vaccine platform. in humans, so we will never know where the good for us will come from and ultimately we want to know what is out there because the next pathogen could be out there.
This new corona virus in China is no surprise that people have been sequencing. viruses in bats throughout China for many years and we found many related corona viruses, so we knew there was an opportunity for what will likely be a bat to spread to humans and that's another reason we're doing this now. You may think that all this is very complicated but, in fact, in the next two

lectures

I will tell you that this can be simplified due to these two facts: first, genomes are obligate molecular parasites that have to enter inside a cell and once they are in the cell they have to be translated by the host's translation machinery, so we're going to use that to take these billions and billions of viruses and simplify them mechanically so you can understand how they work, so next time we'll talk about The infectious cycle, which is what happens when a virus enters a cell until it reproduces, how does it work?
How do we study it?

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