Virology Lectures 2021 #1: What is a Virus?

[Music] welcome to virology i'm vincent draconiello and i am going to be your professor for this entire virology course and this is lecture number one what is a virus a little bit about me before we continue i have been working on viruses since 1976 i've been at columbia i'm at the medical school campus i've been there since 1982 i have a lab that does research on viruses i've been teaching about viruses i've been teaching this course now this is the 11th year and i've written a textbook and done a lot of other things it's my goal to teach you virology to teach as many people in the world as possible all about viruses and before this pandemic at the beginning of every virology course i used to say if you want to understand all about human disease if you want to understand human health you need to know about viruses and that's why i teach this course i actually do it voluntarily i don't have to teach at all being at a medical school but i want you to know about viruses and colombia didn't have a virology course for many years so that's why i'm doing this it's voluntary nobody's forcing me to do it but the fact is i love viruses even though they have caused enormous devastation in the past year they're amazing i'm fascinating with the with them and i have devoted my entire career to them and i want to pass along to you some of my passion for viruses and make you knowledgeable more than most people on the planet there's a lot of misinformation and i want to fix that one student at a time so this is my course for you we live and prosper in a cloud of viruses viruses infect every living thing on the planet there is no life form that does not have some kind of a virus that infects it in fact most have many many different viruses humans regularly eat and breathe billions of virus particles a day you're breathing them right now they're floating around in the air you eat them with your food as we'll see and we carry viral genomes as part of our genetic material every life form on earth has viral genomes as part of their genetic material it is just remarkable and so really in the end we're talking about huge unfathomable numbers of viruses on the planet earth the number of viruses is staggering and this is an example this is just in the world's waters people have gone out and estimated the number of bacteriophage particles in the world's waters bacteriophage which is pictured here is a virus that infects bacteria as the name would indicate bacteria archaea everything is infected with viruses in the world's waters there are over 10 to the 30th bacteriophage particles this is just remarkable that number is too big for you to comprehend i don't get it i don't know what 10 to the 30th is but we can put it in in terms that make more sense next time you go in the ocean you take a mouthful of water and spit it at someone you're spitting millions of virus particles in coastal water in surface water out in the middle of the ocean way down deep everywhere you go millions of virus particles per milliliter because there's a lot of life in the oceans now a phage particle weighs about a femtogram 10 to the minus 15 grams and if you multiply that by 10 to the 30th you find that the biomass on the planet of of bacterial viruses alone exceeds that of elephants by a thousand fold i mean these are things you cannot see that's just remarkable and if you put these phages head to tail they would extend 100 million light years into space that's way outside the planet formerly known or the pluto former planet you know it's just way out there it's it's farther than the nearest galaxy 100 million light years so that's a lot of viruses and you can't see them that's the amazing thing and the extent to which different life forms are infected with viruses is remarkable give you some examples whales are commonly infected with small naked rna-containing viruses called kalisi viruses they may cause various diseases like rashes and blisters and even gastroenteritis some of these viruses can affect us as well but here's the thing infected whales excrete and they excrete in the feces this is an enteric virus in wales over 10 to the 13th kalisi viruses daily one whale 10 to the 13th daily it's just remarkable how many and and many other animals are similarly infected perhaps one goal i have for this course is for you to understand that viruses are not just bad news of course this year everyone is going to think that's all viruses do is make people sick because most people have not thought about viruses before but in fact the vast majority are benign maybe even considered symbiotic so if you look in the ocean and this is another great statistic more viruses and a liter of coastal sea water than there are people on earth that's how many viruses are in the oceans if you look at these two pie charts here the one on the left is looking at um prokaryotes protists and viruses right so protists are eukaryotes and then virus particles by biomass alone and prokaryotes vastly out mass the others there's more massive prokaryotes in the ocean than protests or viruses but if you look at particle number or abundance viruses make up 94 of all particles in the ocean of among these three groups they are in the oceans you may be wondering what are they doing are they just infecting bacteria protists and fish and mammals that live in the ocean well they are but they're not making most of them sick actually they are catalysts for biogeochemical cycling they turn over carbon and sulfur and phosphorus without viruses releasing organic matter the earth would be quite a bad place to live and we're just beginning to understand this so they have huge roles in cycles on the earth another interesting statistic today there are 10 to the six genomes of hiv-1 on the planet human immunodeficiency we have another pandemic going on right now and it's amazing most people don't realize that it's the hiv aids pandemic there are 37 million people infected at the moment and we'll have an entire lecture on hiv aids to emphasize that but we know how many genomes are in each person and we can calculate 10 to the 16 also a huge number and what does it mean well among those genomes because the viral genome is so variable as most rna genomes are there already exist resistance to every antiviral drug we have we have well over 30 antiviral drugs to treat hiv aids that work very well but there's already resistance to all of them out there and no matter how many we make in the future we will have resistance to them because of this genetic diversity that's what that means a number like that what about us how infected are we well we at least have and all of you have these viruses about a dozen herpes viruses in us like herpes simplex one and two varicella zoster human cytomegalovirus epstein-barr virus and then herpes human herpes virus six seven and eight you all get these in your first decade of life and you have them for the rest of your life there's no exception and you can't get rid of them once infected it's for life i love to say unlike love herpes is forever because many of these you get from loving and i get an email on a daily basis i get posting on my social media dr so and so cured me of herpes no it's not possible not today maybe in the future we could do that but these are with you for life and we're going to have a lecture that explains that however we have more than just a dozen herpes viruses as you know we have a microbiome that is unique to each part of our body we have microbes in our mouth in our respiratory system and our skin in our intestines and so forth that have just been characterized in the last 15 years and which are clearly beneficial for us and if we disturb the populations we have problems and many diseases are being linked to the microbiome and the products that they make the metabolic products that they make but we also have a viral and here on the left is a a diagram of what we know of the human virum again every tissue and organ system has its unique complement of viruses and here they're coded whether their dna or rna containing viruses in blue or green by pie charts and your skin your digestive tract your blood etc even your nervous system has viruses just think of this there are viruses in all parts of your body most of them are not making you sick we think that most of them are actually beneficial now in recent years we've developed technologies that allow us to study the microbiome and the virum of course sequencing is a big part of that but here on the right is a movie which i'm going to play for you and this is a drone and on the top of the drone is a a big petri dish a plastic petri dish and this drone is being flown by scientists on a nearby boat this is off the coast of australia and these are whales here you can see the blow coming out of these whales and they want to collect the breath of these whales and see what viruses are in it so what they do is when they fly over the whale they this there's a little mechanism that opens it so let's play it there you go see the lid came up and then it so it came up it caught the mist from the whale breath closes then they go back they bring it back to land and they can sequence and find out what viruses are are in whale breath i couldn't do that before you can't catch a whale as i sit still while i sample your anterior neres it doesn't work this is brilliant a combination of sequencing of course which you need to do this and also the drone technology so we can access a lot of different kinds of wildlife that way as i said earlier our genome contains viral information integrated in it so here's a pie chart of the human genome 3.2 billion bases of course it's been sequenced many times in many many humans and it's divided according to what we've found and you know it's just embarrassing how little is protein-coding genes 1.5 percent the rest is non-coding and has various functions and what i want to point out to you here these ltr retrotransposons these are in some of these are in fact remnants of viral infections retrovirus infections whose feature of their reproductive cycle is to integrate their nucleic acid into our genome and these other signs short interspersed nuclear elements and long interspersed nuclear elements or also retro elements that can move around the genome and these these are beneficial they can also harm us but we have taken some of these viral genes and use them in the course of our evolution and we'll talk about that in this course in fact the placenta would not be here if we didn't have a retrovirus that delivered the sensation gene that's needed for the formation of the placenta of course most people are interested in viruses because they cause disease so here's a cause a chart showing you the causes of 2017 global deaths it's the most recent data i can find and by different causes here and you can see of course cardiovascular diseases are the biggest killer cancers and i've put arrows next to the viral diseases of course lower respiratory infections you can see diarrheal diseases have a lot of viral causes and then where does covid19 fit well we have about 1.9 million deaths so far as of january 4th and that would put it you know just between digestive and neonatal disorders that's a pandemic that's been going for about a year it's quite remarkable we'll certainly have more than far more than that by the time this is over hiv aids hepatitis many hepatitis infections are caused by infections so we try to avert some of this of course by studying viruses and learning how to prevent or resolve infections so let's take a look now at the current numbers i'm going to switch to a live version of this so when i started teaching this course the johns hopkins site which all of you certainly know didn't exist and i have some screen caps where the global cases now 90 million plus global cases this was 5 000 10 00 30 000 and i remember most of the red dots were in china for for many many weeks and and nowhere else and then they slowly started spreading so this is a wonderful website where you can go to learn the numbers the cases the global deaths you can drill down by country as you can see and of course we're leading yeah in cases and in deaths because we've had a really poor response to the pandemic we'll talk more about that later anyway that's a great site there's also a wonderful site in the new york times where they show you um cases in the u.s from uh march until the present and they also have a map of the country where they you know the red the where's the here the redder areas the darker areas have more cases and then they also have a world view so we don't get too us centric latest maps and data that's the world view and they have a map of the world with the heat map of cases as well so lots of great um resources to study this well this is not a course about the pandemic but you're gonna learn virology and you're gonna understand what's going on in the pandemic the vast majority of viruses that infect us as opposed to this one sarsko v2 that's been killing so many people most of the others have no impact on our health or well-being and why is that why is that uh and you know someone asked in the chat why is it that people can have symptoms associated with herpes if we all had it so that's an interesting characteristic of that infection because it goes into latent phases where it's silent and then it reactivates periodically and then you may or may not have disease we'll have an entire lecture on that in this course well many viruses just pass through us you eat them for example in your food and here's a two interesting studies in one they looked at cabbage from five different supermarkets in washington dc and you know cabbages used to make coleslaw of course and each serving would have up to 10 to the eighth particles of a virus that infects the cabbage looper this is a cabbage looper right here on the right caterpillar of cabbage so these caterpillars are crawling over the cabbage and they're shedding viruses you can't wash them off you can't you just can't get them off and it doesn't matter because they pass right through you they cannot infect your cells and we'll study why in that course why they cannot infect your cells here's another example if you take human feces and you sequence the nucleic acid most of the rna virus sequences 91 of the rna in human feces is similar to plant viruses so we eat a lot of plants they have their own viruses we have them in our feces they just pass through they don't infect this you know you can have your fecal virum done now you can send feces to a company and they'll sequence the virum and i routinely get emails from people have this plant virus is it bad is it a problem no it's not a problem they're just going to pass through you the most abundant human fecal virus is pepper mild model virus it's a virus of peppers makes peppers look bad and it's a long flectuous virus as you can see here but it's completely harmless to us 10 to the ninth virus particles per gram of feces but they don't infect us so most viruses just pass through us and that's just the gi tract but same for the respiratory tract your skin uh we are regularly encountering viruses that simply cannot infect us as i said earlier i think many viruses are in fact beneficial not all of them just pass through us many of them reproduce in us but they don't cause disease and i suspect that some of them are beneficial it's hard to look to study that though we can't do the experiments and people that we need to know to do that but here are two examples of beneficial viruses in systems that you can study on the left is a plant called dicanthelium lanuginosum sounds like a harry potter curse right this is a plant that grows at high temperatures if you go to yellowstone national park with all the hot springs these grasses will grow right next to them 55 degrees celsius no problem and they're able to grow because they have inside them a fungus with a virus in the fungus because if you take the virus out of the fungus the plant will not grow at high temperature and so you need both the virus in the fungus for for growing at high temperature so the fungus has a place to live the virus gets to grow in the fungus and the and the grass grows at high temperatures that's an example of beneficial viruses but we can manipulate this in the lab and find out you know and we can't manipulate people to take out their viruses and see what happens here on the right is another amazing one there are lots of examples of this but this is a wasp a parasitoid wasp that lays its eggs inside of insect larvae like a caterpillar and the eggs then will hatch into baby wasps who then eat their way out of the larva and um what was that movie uh aliens right they didn't invent anything it was already in nature the wasp genome has encoded in it viral genes to make virus particles and so when the wasp delivers an egg into the caterpillar it also delivers virus particles these blue dots here it's a polyidna virus it's a big dna virus and the virus delivers genes whose gene products immunosuppress the caterpillar so it won't reject the wasp egg so this virus is good for the wasp of course not so good for the caterpillar because it allows the wasp eggs to hatch and eventually not be rejected there are all kinds of examples of this of how viruses manipulate different hosts to benefit one or the other now there is some evidence in mammals that viruses are beneficial for example uh this is an example of mice uh who's whose enteric tracts uh develop properly because of a norovirus a norovirus is related to those viruses of whales that i told you about earlier so it turns out this is these are sections of the intestinal tract of mice you can see the villi right if you might if you grow uh mice in a germ-free facility that is without bacteria their intestinal tract is aberrant so the villi are morphologically apparent in the control the conventional mice are here this is the control mice that have the normal complement of bacteria so they're morphologically aberrant and their immune system isn't properly developed here on the bottom we're staining for cd3 cells which are lymphocytes and you can see the normal mice have the brown staining cells those are the immune cells in the germ-free mice don't so there's a defect in the morphology of the gut and in the number of immune cells if you grow mice without bacteria you can infect these mice with a muri norovirus and partially restore all of this so here you have now lymphocytes returning to the villi and the morphology is a little better it's not completely normal but it's just one virus if you infect these mice and this is a myrin virus it partially restores the functions that are lost when you take away the bacteria i just think this is amazing now what about in people we don't have any data because we haven't been able to study we can't take away viruses in a similar way although one day when we have broadly acting antivirals we may be able to find out the other reason why many viruses don't hurt us is we have an amazing immune system so all those herpes viruses that are in you they're kept in check most of the time by your immune system many other viruses that infect us are also controlled by this immune system which we'll explore very briefly in this course two lectures or so uh but uh we'll explore the interactions of this system with viruses and to emphasize how amazing this immune system is when your immune system is down if you're immunosuppressed for example if you are on drugs to take care of a cancer they can immunosuppress you many virus infections can immunosuppress you hiv aids measles virus and others and then you have problems and if you take immunosuppressive therapy for example for various diseases all these viruses that are in us can be a problem and so liver transplants when you get a liver you get immunosuppressive drugs and then human cytomegalovirus begins to reproduce and cause problems you have it in you we all do and normally it's kept in check but if you're immunosuppressed then the viruses can cause pathology so viruses not only pass through us they're reproducing us they're kept in check by our immune system and there are many that reproduce in us but don't make us sick and we'll explore some of these later here's a polyoma virus a small dna containing viruses that infect everyone over 90 percent of the planet is sero-positive and they're slightly different kinds of polyoma viruses you get these in your family they're spread within your family and so as your first 10 years of life you get it from your parents and siblings and we can trace population movements by what kinds of polyoma viruses they've been affected with so here's a map of a human population movement the dotted purple line is reconstructed by genetic analysis of populations human populations so humans moving out of africa into europe and asia and eventually into the americas right the black line is reconstructing human movements based on polyoma virus infections much more granular as you can see you can even see moving into australia these are viruses that don't hurt you again unless you're immunosuppressed now in a bigger picture viruses clearly shape host populations and vice versa so when a virus is introduced into a population as you have seen last year with sarsko v2 it kills a lot of people it can shape the population and similarly if a virus doesn't have a host if the host is gone if the host becomes extinct there's no more of that virus so it's a two-way street and here's an example which i love because this is a example of a virus that infects these uh eukaryotic phytoplankton that bloom in the ocean you can see them from space this is a satellite photograph of one of these blooms the organism is emiliano huxley eye and these blooms get big and then viruses infect them and then the blooms go away the blooms are collapsed so that's an example of how a virus can affect a population there are many many examples and we'll explore some of those later on in evolution so in short viruses are amazing you've just never seen anything like it you're going to love this course you're going to love what you learned you're going to be amazed but what i want to leave you with just before we go into some detail is that virology is an integrative science what do i mean by that you need to know everything to understand viruses you just there's no subject just a virology virology to understand viruses you have to know cell biology biochemistry uh physiology even ecology even is sociology to see how populations interact epidemiology and many more so that's what i mean by integrative it brings together all these different disciplines and i've had many students tell me you know i took biology as a freshman most of it didn't make sense but in the context of viruses now it all makes sense that's the beauty of virology because you need to understand all about how cells work to understand virology and my goals for this course are shown here i want to teach you the big picture this course is not about individual viruses you can find lots of virology courses where lecture one is influenza virus lecture two is herpes lecture threes coronavirus you're not going to learn virology that way that's why our textbook is written by principle we take a core set of viruses and we teach you how viruses work how they cause disease and that's what we're going to do in this course this this course is designed around the textbook so i want you to learn about virology as an integrated discipline i'm not going to teach you about viruses i'm not going to teach you about diseases or genes we're going to put the whole picture together and in the end you're going to have a better understanding and then you could take an advanced course where you delve into specific viruses and perhaps the most important one in these days of misinformation you're going to learn things that i say amaze the informed and frighten the uninformed people typically are afraid when they don't understand something and in this pandemic we've seen so many examples of how people want to blame others for example for the origin of the virus they want to blame a lab in china which you'll see is just absurd it reflects a lack of understanding of virology and i want to teach you that but even more important i want you to be able to read a newspaper headline and understand when it's right and when it's wrong and my my interaction with mainstream media over the years and it's not just this year has always been tempestuous because at least the people who write the headlines need to take a virology course so here are some examples this actually are some headlines from last year but every time there's an outbreak it's the same coronavirus could mutate coronavirus could mutate and hear the vice minister in china there is the possibility of viral mutation and then just recently in the new york times the coronavirus is mutating you will learn in this course why these headlines drive me crazy the virus is always mutating always at every reproduction cycle in every cell in your body that's infected that's always mutating the question is whether it means anything so these headlines are crazy and i want you to learn how to distinguish truth from not truth in in virology reporting we are going to do these quizzes throughout the lectures so that you get a break from listening to me and i can see if i've been teaching you so what you have to do is go to this website and it will ask you for a room number and the room number is virus of course and here and go there now and and take this quiz which statement is true all viruses make us sick and can be lethal our immune system can manage most infections humans are usually infected with one virus at a time the press is usually correct in their virology reporting our immune system cannot handle most viral infections looks like most people got selected b which is our immune system can handle most infections that's correct all viruses make us sick and lethal is incorrect we are infected with one virus at a time of course is not correct the press is usually not correct well that's probably harsh but you can see why that would be false and our immune system can handle most virus infections what is a virus that's the name of this lecture so let's define it here's my definition which has changed over the years an infectious obligate intracellular parasite comprising genetic material and that can be dna or rna often surrounded by a protein coating sometimes a membrane so let's let's break it down and infectious that that's clear infectious means it can go from cell to cell or host to host obligate intracellular parasite so obligate intracellular means the virus has to get into a cell in order to reproduce if it doesn't get in the cell that's the end of that virus needs to get inside and parasite of course means one organism taking something from another so viruses can take your life or they can take materials that they need in order to reproduce it can be very subtle or can be very dramatic genetic material dna or rna viruses are unusual because some viruses have rna and there's nothing else on the planet that has rna as its genetic material we have dna everybody else has dna there are some viruses that have rna like sars cov2 and of course that is because probably the first life molecules that evolved on earth were rna molecules and the first life forms were rna-based so viruses rna viruses are relics of what we call an rna world and we'll talk more about that later and these genomes can be surrounded by a protein code so here for example um is poliovirus the virus i've spent my entire career working on it's just a piece of rna with a protein shell here's adenovirus which is being used to make some of the vaccines being used as a vector and it's again dna with a protein shell and sometimes there's a membrane so let's go right to coronaviruses here it's an rna virus with a membrane and in that membrane of course our spike glycoproteins and other kinds of glycoproteins here's influenza virus again a membrane with spikes in the membrane so that's the fundamental structure and that's the fundamental definition we'll look into how these viruses are built in a subsequent lecture so viruses are obligate molecular parasites they need the machinery of the host cell so when you study a virus and you learn about it you learn about the cell and countless cellular processes have been understood by studying viruses almost every major cellular pathway for example dna synthesis was first figured out using a virus the structure of messenger rna was figured out using viruses splicing of messenger rna was discovered with viruses they're amazing systems for studying the host cell now a very interesting question that many people have and they're very opinionated about is are viruses alive and i used to have a a poll on my blog it's not there anymore but our virus is alive and you can see it's evenly split between yes and no and something in between but i over the years have thought a lot about this and there's quite a straightforward answer and it really depends on what you mean by virus so let me explain a virus is an organism with two phases there's the virus particle which you all think of when you think of virus right the pictures of coronaviruses and all the viruses i've just shown you that's the virus particle there's no way that that can be alive it's a piece of nucleic acid surrounded by protein and sometimes a membrane can't do anything it cannot reproduce on its own however when it infects the cell it actually reprograms the cell to make more virus particles and so the cell of course the infected cell is clearly living but the virus particle is not so this solves the conundrum when you say virus what you are meaning is an organism with two phases there's the infectious particle which is not living and there's the infected cell which is clearly alive and it's dedicated to making virus particles and so you know many people say oh the viruses have the potential to be alive yes when they infect the cell but the particle is not it just cannot be the other thing i want to warn you about and will probably remind you multiple times is to avoid anthropomorphic analyses now science journalists love to use these because it makes it easier to explain science but viruses do not have human qualities they do not think they do not employ ensure exhibit display and do any of those active words they are passive agents everything that happens is a passive activity a virus bumps into a cell and if it happens to have a receptor the virus binds and then gets in there's no active part of it and so they do not achieve their goals in a human centric manner the danger with saying viruses are thinking about doing this is that you apply human values to what viruses are doing and we have no idea if that's correct you know saying the virus wants to become more transmissible is absolutely wrong it doesn't have any desires but if you apply your human sensibility to virology you're going to misunderstand what happens and so that's the key here it's more than just semantics it's a matter of whether you view viral processes on their own as they should be or through a human lens which is not correct and again there are many examples of this happening in the popular literature the other part of the definition that used to be part of the definition of virus is that they were small but i've taken that out because many of them in fact are small but many of them are pretty big as we've discovered recently so here just to give you a sense of scale here's an e coli at 100 000 x and there's a bacteriophage of e coli attached to it next to the phase this rod-like structure that's a tobacco mosaic virus it's a virus of tobacco so they're they're much smaller than the e coli of course but you know comparable scale and then d is actually hiv-1 so it's quite large and then a is a panel which is expanded on the right a million fold and here is a polio virus h and a g is a ribosome so the poliovirus and ribosomes are very similar in size and there's a trna an antibody molecule a is supposed to be a carbon atom but of course it should be much smaller and here are some you know actin and myosin cables and some some enzymes so viruses can range from the very small you think you can't see these with a naked eye and in fact here's a diagram that shows that in a more clarity so here's a scale size going from a centimeter to an angstrom which is you know 10 to the minus 10th meters and we have atoms down there all the way through cells and viruses are somewhere in between bacteria and ribosomes in their scale and depending on what you're studying you know we can use a light microscope light microscope doesn't work for most viruses you have to use an electron microscope or cryoelectron microscopy and of course for proteins and atoms we need x-ray crystallography and nmr and we'll see how we use these technologies to study virus particles but here's the cell again to show you scale a eukaryotic cell with a nucleus and coming out of it are herpes viruses and polio viruses so here this area is expanded there's a herpes virus about 200 nanometers in diameter and the poliovirus about 30 nanometers about 10 times smaller and ribosomes about 20 nanometers so i want you to get used to these size measurements because i'll be using these terms nanometers quite often throughout this course and of course you're all wanting to know how many viruses can fit on the head of a pin and here's the answer so pin is about two millimeters in diameter and that is a dust mite right there in pink that's a hair lying across the top of the pin and in the middle is something but you can't quite see it and that's expanded on the right and here we have some pollen and some lymphocytes these are red blood cells these are bacteria in green and then right in the middle there are some virus particles the biggest one is actually ebola virus and the others you can't even see but you can put 500 million rhinoviruses rhinoviruses are the common cold viruses they're about the same size as poliovirus 500 million rhinoviruses on the head of a pin and when you sneeze the droplets that you expel can be larger than the head of a pin so you have enormous capacity to expel lots of viruses to infect other people and that's how viruses are transmitted of course in part and why they are so effective and we'll talk about those later now viruses as i said in the definition of viruses we used to say small obligate intracellular we took small out because we have now discovered huge viruses and here's one mimi virus was the first giant virus discovered that's what we call them giant viruses and for comparison rhinovirus there 30 nanometers you can see this is this is about 700 nanometers in diameter hiv bigger than rhinovirus but dwarfed by mimi and here's an electron micrograph of of two mimi viruses in an infected cell even bigger viruses have been since discovered here is one called pandora virus because its genome is so huge it's like opening a pen actually the pandora's was not a box actually it was a it was a flask of some kind and this was flask liked but this is a big dna virus that infected amoeba and this is a light microscopy photograph of pandora virus particles they're about a thousand nanometers in length you can see them under a light microscope not very not many viruses can be visible in a light microscope this is huge the genome is is huge as well and here's a graph of virus particle size versus genome size to emphasize this here's a polymor virus which we talked about quite small herpes virus is 200 nanometers and the vaccinia virus or smallpox virus relative is even bigger and then we have our mimi virus here about 700 nanometers and you can see there's our pandora virus and even bigger viruses have been found pithovirus 1500 nanometers in length with huge genomes so small is out of the definition of virus particles now a key property of how viruses work is they replicate by assembly of pre-formed components you make the parts you assemble the virus particle it's very different from bacteria which of course reproduced by binary fission you put a bacterium a single bacterium in a broth and it begins to double from one you have two and four and eight and so forth binary fission viruses don't do that when you put viruses into cells for a while you don't see anything because during this eclipse period the parts are being made then they're assembled and you then begin to see the infectious particles made this was a key differentiator from early scientists who were studying viruses how they were different from bacteria which of the following is true concerning bacterial versus viral replication viruses must assemble using pre-formed components bacteria do not replicate via binary fission as viruses do bacteria must assemble using pre-formed components viruses do not have an eclipse period viruses replicate by binary fission someone asks in the chat why does it take longer to find huge viruses and one would think smaller ones would be harder to find you know it's a good question we're only discovered 15 years ago all of them infect amoeba and nobody was looking for amiibo viruses and i have to say that first mimi virus was first seen in a in a specimen and they thought it was a bacteria so they put it in the freezer and forgot it for 10 years because it was too big we weren't thinking about such big viruses and now we show the results there we go that's what i was looking for before the right answer which most of you got is a viruses must assemble using pre-formed components the others are all wrong bacteria do not replicate binary fission of course they do replicate by binary fission bacteria don't assemble using preformed components and viruses do not have an eclipse they do they have a period where you can't see any new virus particles how old are viruses and in this one study a virus so now what we can do is we can sequence viral genomes and we can estimate how old they are by a variety of techniques that we'll talk about later and in one study some retroviruses were suggested to have arisen 450 million years ago in the ordovician period which is right here on the timeline of of life right first land plants are rising so these arose in the oceans first 450 million years ago when organisms like this one were swimming around but that's only because we have some data that suggests that i think these viruses originated before cells they were pieces of rna just replicating in the primordial soup and they were precursors of cells actually and we'll talk more about that in detail so probably they've been around for billions of years although you know before cells is a very different thing than we think about now i think viruses arose as self-replicating nucleic acids from then arose cells and then the viruses went into the cells because it was easier to reproduce in the cells than outside of cells but we fast forward many many billions of years we can see some ancient references to viral diseases this this uh amphora from 700 bc says on it here this fire brand rabbit hector so rabid referring to rabies which was a disease that occurred and was not known to be caused by a virus of course and then this is a egyptian carving from 1500 years bc and this priest has a dropped foot which is characteristic of polio the leg becomes paralyzed and you can't hold the foot up any longer because you need muscles to do that so it drops it's flaccid paralysis it's typical of poliomyelitis in the 1700s or actually the 11th century in china they practice a method called variolation so by this time were many diseases known how they developed was not known but they were known to be contagious and so for example smallpox was already known in the 11th century and it was known that some people who recovered from smallpox never got it again so they did this practice where they would take some smallpox pustules and inoculate them into people to immunize them we would call that today was called verilation and here you have an example of the the pustule actually being blown into the nose of a person because this smallpox is acquired by respiratory inhalation about 30 of these individuals would die so not a great vaccine by today's standards but it did protect some of the population in the 1700s the wife of the british ambassador to turkey noticed this process or this practice in turkey she brought it back to the uk and it spread throughout the uk and this was all without knowing what the agent was but simply that the survivors were protected and finally in the 1790s experiments by edward jenner in england establish vaccination and from then on is history we'll talk about that in our vaccine lecture but when did the concept of microorganisms and viruses arise this is very interesting history it begins with three individuals at different times liven hook pasteur and koch and leuvenhook of course developed a microscope and you know people used to think whatever you could see that was all there was on the earth and loisenhook said no there's stuff in water there's all kinds of small things swimming around the concept of microorganisms something smaller than what we see in what you need a microscope to see pasteur then in the 1800s developed this idea that there are bacteria microscopic bacteria that can reproduce that they do not arise by spontaneous generation his famous swan necked broth experiment where he sterilized broth and showed it remained sterile until you broke the neck of this flask and the bacteria could be used to make good things like wine and beer and cheese so that's pasteur microorganisms and then cooked working in germany said you know these bacteria not just for wine and cheese they can make you sick so he developed the germ theory of disease he said some bacteria can cause diseases however no no viruses yet the technology isn't good enough so what when did we learn about viruses well if you look in the literature as early as this 1728 virus was used to describe an agent that causes infectious disease and virus comes from the latin word meaning poison so they're thought to be liquids know that they were particular and pasteur has said every virus is a microbe so he thought the things causing disease are microbes my bacteria for example that are growing okay a key event in the evolution of viruses is is a an apparatus made by chamberlain who worked with pasteur and he developed this porcelain filter to sterilize water water in those days was horribly contaminated you could just apply a vacuum to this filter pour the water in it would go through the porcelain and it would sterilize it it removes bacteria and pasteur found he was working on rabies agent he he found that the agent of rabies passed through these filters it's pretty small so he said it's a small bacterium okay then at the end of the 1800s people are already smoking tobacco is a big industry and it turns out that some of the tobacco can get diseases this is called tobacco mosaic the leaves become blotched and you can't sell the tobacco doesn't make good cigar or cigarettes so a lot of people were working on figuring out what was causing it so what they would do is grind up the leaves pass them through chamberlain's filter and see where the agent was and two different individuals in 1892 and 1898 found that something that passed through this filter could cause tobacco mosaic disease and remember the filter retains bacteria and so something really small is going through it and today we have similar filters that you can buy and use in the laboratory they're 0.2 micron filters that retain bacteria but let viruses pass through them first animal virus was discovered in 1898 again the agent of foot and mouth disease a virus that causes infection of cattle is filterable it passes through the filter that would retain bacteria so the key concept here is that the agent is small but also these agents don't replicate in broth you have to put them in a host either a tobacco leaf or a cow they will not reproduce in broth and again the filter size was 0.2 micron but they were still thought to be liquids at this point that's why they were going through the filter and after that point lots of new viruses were discovered the first human virus yellow fever rabies smallpox polio and chicken leukemia all the way through 1933 where we first identified influenza virus well after the first that big 1918 pandemic and so these are all called filterable viruses the idea that they can pass through a filter and we didn't know that they were particulate and the the pace of discovery is shown here once coke showed how to grow bacteria the pace of bacterial discovery grows really quickly viruses in red filterable viruses they were still called here's the discovery of tmv and then many many more were discovered but in 1939 the key experiment is done by helmut ruska he built the first electron microscope in germany in 1933 and he took the first electron micrographs of bacteriophage he said what is this filterable virus let's take a look at it and he did and he saw there were particles they're not liquids so 1939 well after influenza viruses discovered we finally drop filterable from the name and now they're viruses they're particulate agents okay last question here which is a key concept first discovered about viruses that distinguish them from other microorganisms too large to pass through a 0.2 micron filter uh replicate only in broth they made tobacco plants sick they were small enough to pass through 0.2 micron filter or none of the above so most of you got d they were small enough to pass through a 0.02 micron filter that was the first key concept not too large they don't replicate in broth of course they do make tobacco plants sick but so do bacteria could do that as well so that's not a key concept so in 1939 this experiment was done which i've already showed you and that proved that viruses were not simply small bacteria so it's the same time as the em was done that i showed you and they did a growth curve so again if you put bacteria in broth they begin to divide immediately because they simply divide by binary fission if you put a virus onto cells remember if you put a virus in broth nothing will happen but if you infect cells there's an eclipse period during which you don't see any new viruses made and what's happening there is the parts are being made and then they're assembled and then you get virus infectivity we'll discuss this growth curve that's what it's called next time in more detail so that showed that viruses were not simply small bacteria because they had this eclipse period they didn't divide by binary fission a really different way of reproducing and as time went on we begin to have pictures electron micrographs of more viruses bacteriophage tobacco mosaic virus there and be the rod like particle rabies virus bullet shaped and round viruses today we know incredible details about viruses we have three-dimensional structures of many viruses like poliovirus shown here we even know the chemical formula for poliovirus because we know every atom every atom of rna and protein in the virus particle and we classify viruses and you'll encounter this throughout this course and you've already heard it when you say someone say sarskov2 is a coronavirus what does that mean to be a coronavirus well when we find a new virus we classify it and mostly by the sequence of the nucleic acid and as you'll see back in january last year the sars kofi ii virus was identified the genome was sequenced and immediately it told us it was a coronavirus by homology with other coronaviruses but other properties that are important the kind of shell it has the whether or not there's an envelope and the dimensions of the virus particle this top one the sequence of the nucleic acids only been possible in the last 40 years as sequencing has emerged and before that it was the other properties that we used and we use a very formal hierarchical system of classifying viruses very much like other organisms kingdom phylum class order family genus species and so forth and there's actually more granularity but you don't need to know that there's a website that keeps all the classification in order and mainly in this course we'll be talking about families like the philo viradi family or the coronaviridi family these are families of genera of viruses and within them we have species now technically viruses don't exist as species because the species definition means two organisms that cannot produce offspring but we use it as as a simply a classification mechanism and virus discovery which was once driven only by disease all of those early viruses that i showed you yellow fever polio virus smallpox they were all driven by saying oh there's a new disease let's find out what's causing it and they found viruses nowadays we just look for viruses by genome sequencing and here's a fascinating study published a couple years ago where investigators collected a variety of insects crustaceans nematodes mollusks small critters i would say and they extracted the nucleic acid and sequenced them and they found 1445 new viruses from 220 invertebrate species and this is what we do now we simply extract nucleic acid and we look for viruses and we find them by the score we find thousands just doing a study like this you can find thousands of new viruses and this has hardly been done for any species like rodents we hardly know what's in rodents and they're a threat to humans because any animal that lives in large numbers and close to humans is a threat for a pandemic spillover now you may say why do we care about sequencing all the viruses out there and that's really our goal we want to know everything that's out there well viruses are the greatest biodiversity on the planet they outnumber cellular life by 10 to 1. there are more virus genes than anything else we got to know that just just no way we can ignore it as i said just briefly they drive global biogeochemical cycles they make the earth work they're the reason why carbon is released in the ocean because of viruses they shape host populations and the host-shaped virus populations we'll see evidence of that throughout this course we suspect that many of them are beneficial we can see that in other host systems and probably also in humans as well and of course they are the sources of new pathogens obviously bats are a source of the coronavirus that has caused the pandemic for the past year we don't really know what's in bats for the most part we've hardly sampled them mainly in china but many other countries have bats they have coronaviruses we need to know what's in them and next from bats are rodents which also are numerous and live close to humans i would say any mammal is likely to harbor viruses that can be a threat to us and we we don't do enough studying to understand what's out there now you can see that the viral world is huge but we can order it and that's one of my goals in this course there's an underlying simplicity to viruses because of two very simple facts first the genome is a molecular parasite it will only function in a cell and so we can see what it needs from the cell and that can help us to clarify how it works and then all viruses have to make messenger rna that the host translates no virus encodes a translation system every virus on the planet has to be translated its mrna has to be translated by the host translation system so the mrna must be compatible with the host cell so we can use these two features to organize all of the viruses out there the millions and millions of different kinds of viruses into a scheme that makes sense and makes it easier for us to study them and we'll start doing that in the next couple of lectures now someone asked how many viruses were discovered in the cave you recently talked about on twiv well the the cave you might be talking about the cave full of bats you know caves can have millions of bats in them and if you sample the easiest way to sample bats is to go in the cave you should be gowned up to protect yourself you can collect the guano the bat poop that's on the floor of the cave and bring it back and sequence it and you can find thousands and thousands of viruses but it's barely been done anywhere and you know one thing that's quite interesting is that many farmers in parts of the world collect bat guano to fertilize their fields so you can immediately see how they can infect themselves with some viruses that does it for lecture one next time we're going to talk about the infectious cycle we're going to see what viruses what happens when a virus gets into a cell what are the different things that we can distinguish you

Channel: Vincent Racaniello

Views: 93,541

Rating: 4.9372168 out of 5

Keywords: virus, viruses, viral, virology, pandemic, coronavirus, COVID-19, lecture, course

Id: jX3MhWWi6n4

Length: 61min 57sec (3717 seconds)

Published: Tue Jan 12 2021