Transcript for:
Animal Viruses and Prions Overview

this is the lecture for chapter 13 viruses and prions part two in this part of the lecture i'm going to focus on the animal viruses and then at the end i will go over prions so as a review for the structure for animal viruses all animal viruses must must have a capsid which is composed of capsules and they must also have some sort of nucleic acid so the nucleic acid could be dna or rna also some animal viruses may have an envelope but that is not required for all animal viruses so all animal viruses will have some type of capsid and some sort of nucleic acid and some may have an envelope like bacteriophages animal viruses also go through the five stages of the viral life cycle and as you remember those stages are attachment penetration biosynthesis maturation and release and knowing the structure of the animal virus will allow you to determine the details of each of these stages knowing the outer covering what is the outermost layer of the animal virus will help you to determine how it attaches penetrates and releases from the host cell so all of these are dependent on what is the outermost covering is it just the capsid or is there an envelope so knowing that about the virus will give you information on how it attaches penetrates and releases biosynthesis and maturation this is determined by the type of genome that the virus has so is it a dna virus or an rna virus knowing that information will give you information or give you the location of biosynthesis and maturation so in determining the complete viral life cycle of an animal virus you need to know what the outer covering is is it a capsid or an envelope and you also need to know what type of genome does it have as long as you know those two pieces of information you can give a full of viral life cycle the first thing i want to do is go over how the outermost covering affects the life cycle of an animal virus and the two types of outer coverings are either just having a capsid or an envelope and if the virus has just a capsid i refer to it as a naked virus so that's also known as a non-enveloped virus so a naked virus or non-enveloped virus is just a capsid on the outside there is no envelope so this outermost covering is made of capsimirs which are proteins and remember when i talked about the viruses before on these especially on polyhedral viruses but on all naked viruses you have these protein fibers that are sticking out from the corners and this is what the virus is going to use for attachment so that first stage in the viral life cycle for a naked virus that that virus will use these protein fibers to recognize and adhere to the host cell the next stage in the viral life cycle is penetration so for a naked virus or a non-enveloped virus it will use receptor mediated endocytosis as its method of penetration remember penetration is how the virus gets its genome into the host cell receptor-mediated endocytosis means that the virus and we'll pretend that these purple triangles are the virus the virus will bind to a receptor so the virus will use those protein fibers to bind to receptor and that will send a signal into the cell to perform endocytosis so the cell will actually perform endocytosis moving its cytoskeleton and membrane to pinch off a vesicle and that brings the virus into the cell so the virus is basically tricking the cell into taking it in by endocytosis so again this is receptor-mediated endocytosis the endocytosis only occurs when the virus binds to the receptor and once it is in inside the cell the whole virus went into the cell so it's not just the genome like with the bacteriophages it's the capsid and the genome so then the animal virus the naked virus has to go through a process of uncoding and that is where the capsid is removed so the protein capsid is removed so then you end up with just the genome inside the cell now i'm just talking about a naked virus or a non-enveloped virus and so i went through attachment and penetration and if all you know about the virus is that it is a naked virus that gives you no information on biosynthesis or maturation you need to know what kind of genome is present for that information but it does give you information on release and naked viruses released by lysis so they release by lysis so the cell will rupture and of course that will kill the cell cell cannot survive that process now i want to go through the life cycle of an enveloped virus and so remember knowing the outermost covering will give you information on attachment penetration and release and as a reminder the envelope is composed mainly of a phospholipid bilayer so it's composed of a phospholipid bilayer which is very similar to the cell membrane of the host cell the other thing to remember is that embedded in that phospholipid bilayer are viral spikes so these are protein spikes that were encoded by genes on the virus so these are proteins and they are considered spikes so when the cell is going to attach when an envelope cell is going to attach to a host cell it will use these spikes to bind to receptors on the host cell so this is an example of a virus and this is the host cell and here's the enveloped virus so the envelope is on the outside here with those spiral spikes inside is the capsid and inside the capsid is the nucleic acid so these viral spikes are going to recognize receptors on the appropriate host cell so again those spikes are used for attachment then penetration is going to be done by fusion and fusion means that the envelope and the host cell membrane are going to fuse together and that is fusion and that is something that phospholipid bilayers can do when you bring two phospholipid bilayers in close contact extreme extremely close contact they will fuse together so they will fuse together creating one phospholipid bilayer like that when that happens then the capsid with the nucleic acid can enter into the cell and again because the capsid has entered into the cell this virus has to go through uncoding where that capsid is removed and then just the nucleic acid is released into the cell so an envelope virus will use its spikes for attachment then it will penetrate by fusion biosynthesis and maturation are determined by the type of genome so if all you know about the virus is that it's enveloped you don't know where biosynthesis and maturation are taking place but you do know that this envelope virus will release by budding so at the end of maturation you have the capsid that has been assembled around the nucleic acid and then that capsid will be transported to the edge of the membrane of the host cell and then that membrane will start to bud out and the membrane will bud out enough that you will pinch off a vesicle and that is what gives rise to the envelope so the envelope actually is derived from the host cell's membrane and that is the process of budding knowing if a virus is naked or enveloped will give you information on attachment penetration and release to know where biosynthesis and maturation take place you need to know what type of genome the virus has so now what i want to do is go through the dna viruses and on your list of microbes to memorize you have several dna viruses that you need to know first are the herpes virus so you have herpes simplex 1 which is the cold sore herpes simplex 2 is the std and also chickenpox so remember that chickenpox is actually a type of herpes virus then another type of dna virus that is on your list is hepatovirus hepatovirus which i've mentioned before can cause hepatitis it affects the liver another one is papova virus papova virus causes warts and those could be the warts that you see on the hands and feet and also it includes hpv human papilloma virus which is or causes genital warts and the last type of dna virus that you should know are the pox viruses and an example of this is smallpox and this is an old picture of a child with smallpox because smallpox has actually been eliminated so there are no natural cases of smallpox anymore in the world because we eliminated the disease by a process of vaccination so these are examples of dna viruses knowing that a virus is a dna virus will give you information on biosynthesis and maturation so if the only information you have is that the genome is dna and you don't know if it's a naked or enveloped virus then you won't have any information about how it attaches penetrates or release but you will have information on where biosynthesis takes place and where maturation takes place so for biosynthesis remember that there are two things that have to be produced first is that the virus needs to make copies of its genome so in this case the genome is dna and in a normal eukaryotic cell dna is replicated in the nucleus so that means that copies of the dna viruses genome will be made in the nucleus because that's where all the enzymes are located the second thing that has to be synthesized during this stage are the capsumeers and the capsimirs remember are made of protein so those will be made by the ribosomes and the ribosomes are found in the cytoplasm of a eukaryotic cell and remember the cytoplasm is the area between the cell membrane and the nucleus so these ribosomes are found on the rough er and also floating free in the cytoplasm so during biosynthesis the genome copies of the genome will be made in the nucleus and the capsamers will be made in the cytoplasm so for maturation you have to get these two components together and if you remember when i talked about the nucleus that dna never naturally leaves the nucleus but proteins can be transported into the nucleus so for maturation to take place in a eukaryotic cell that will have to occur in the nucleus because that's the normal direction of transport proteins can move into the nucleus dna cannot move out papova virus is the group of viruses that includes hpv and causes all the different types of warts is a naked so it just has an outer covering of a capsid it's a naked virus with a dna genome and so now that you know the outer covering it's a naked virus and you know the genome dna virus now you can describe the complete viral life cycle of papova virus so going through the first stage for attachment the papova virus would use those protein fibers to recognize and adhere to the appropriate receptors on the host cell then it would penetrate by receptor mediated endocytosis after it penetrates it will go through encoding because remember the whole capsid penetrates then the genome the viral genome will be transported to the nucleus and in the nucleus that is where you will get copies of the viral genome made and then the capsumeers will be made in the cytoplasm so biosynthesis is occurring in two locations the genome is being replicated in the nucleus the capsulmeres are made in the cytoplasm then for maturation the capsimirs will be transported to the nucleus and maturation will occur in the nucleus once the virus particles are all pred are all assembled then the virus will release by lysis rna viruses are the other type of virus that i want to talk about and with rna viruses on your microbes to memorize sheet there are lots of different types of rna viruses and i didn't have any good pictures of those but for these you have the coronavirus which includes of course covid19 filoviruses include ebola flavia viruses include several diseases such as yellow fever and dengue fever and zika coronaviruses are known mainly for the common cold paramioxiviruses measles mumps orthomyoxaviruses influenza rhabdoviruses rabies and the last group the retroviruses they are technically an rna virus their genome is composed of rna but they are a special group so i will talk about them separately after i go through the rna viruses if all you know about a virus is that it is an rna virus then you have no information on how it attaches penetrates or releases from the host cell but that does give you information on biosynthesis and maturation so remember for biosynthesis you are synthesizing two things copies of the genome and cap smears and for the genome the genome is composed of rna and in the cell the copies of the rna will be made in the cytoplasm so not in the nucleus capsmere as i talked about before capsamers are proteins so those will be made by the ribosomes which are out in the cytoplasm so for maturation both of your components are in the cytoplasm the copies of the genome are in the cytoplasm the capsimirs are in the cytoplasm so maturation will also occur in the cytoplasm coronavirus causes many diseases like the common cold and all picorna viruses are naked rna viruses so now that you know a picornovirus is a naked rna virus then you are able to give me the full life cycle so naked virus will use its protein fibers to adhere attach to the host cell recognize and attached to the host cell then it will penetrate by receptor mediated endocytosis and also it has to go through uncoating because again the whole capsid has entered the cell once it goes through encoding then it goes through biosynthesis copies of the genome will be made in the cytoplasm cap smears will be made in the cytoplasm so because these two components are both in the cytoplasm you get maturation in the cytoplasm and then a naked virus releases by lysis within the group of rna viruses there is actually a lot of variation in their genomes some rna viruses their genome can be made a positive sense some can be made of negative sense rna some can be single stranded some can be double stranded and all of those differences in the genome can have little effects on the viral life cycle but that is the level of detail that i don't think you need to know at this point but i just want to point out that no matter which type of genome the rna virus has always with all of them the biosynthesis is in the cytoplasm so that doesn't change that general rule that i've given you so rna viruses always have biosynthesis in the cytoplasm and maturation in the cytoplasm technically retroviruses are a type of rna virus because their genome is composed of rna but they have a slightly different life cycle that i want to go through there are many types of retroviruses but the most famous one is human immunodeficiency virus or otherwise known as hiv and all retroviruses have the same basic structure so all of the retroviruses are enveloped so they do have that phospholipid bilayer and they do have those spikes embedded in the phospholipid bilayer and then of course like all viruses they have a capsid which is composed of the capsimirs those protein capsules and then as i mentioned before their genome is composed of rna now an additional thing that retroviruses have is they actually contain an enzyme and the enzyme is called reverse transcriptase and you know that's an enzyme because it ends in ace and the name is actually very descriptive because this enzyme does the reverse of transcription so if you remember from your basic genetics transcription is the process by which dna is copied into rna so what would the reverse of that be it would be taking rna and making a copy in dna and when that is done by the reverse transcriptase we call that v dna little v dna that means viral dna so reverse transcriptase is an enzyme that will convert the viral rna into a dna copy and animal cells never do that so human cells never take rna and make a dna copy so that is why the virus has to carry the enzyme with it because the host cell will not have that enzyme there is a second type of retrovirus on your microbes to memorize lists that i want you to know and it is murine mammary tumor virus otherwise known as mmtv and marine mammary tumor virus this is actually the animal model for breast cancer so that mammary tumor breast cancer and murine tells you what kind of animal it is specific for and urine refers to mice so like canine is for dog feline is for cats mirin refers to mice so if we want to use the mouse as a model for breast cancer we need to infect the mouse with this virus the mmtv and then the mouse develops breast cancer now a retrovirus is an enveloped rna virus so this will follow the life cycle the basic life cycle for enveloped rna viruses but there will be a little twist to it but in general enveloped rna viruses will use the spikes spikes for attachment for identification and attachment of a appropriate host cell then for penetration they will penetrate by fusion and then for biosynthesis since it's an rna virus that will occur in the cytoplasm and maturation will also occur in the cytoplasm and they will release by budding and budding by the way does not kill the cell because the cell membrane remains intact so budding will not kill the cell the cell can still remain alive so a retrovirus will follow this basic life cycle but the difference occurs during or right after penetration for a retrovirus so as soon as the virus goes through uncoding the reverse transcriptase is going to copy the rna genome the viral rna into dna so that's the dna so it's going to make a copy of the viral genome into dna and then that viral dna is going to transport to the nucleus and it's going to splice into the cell's chromosome chromosome so the host cells dna and when it does this it forms what we call a pro virus when it does this the host cell doesn't know anything has happened and the host cell can continue doing what it does so it can continue metabolizing moving reacting so it continues doing everything it normally would until there's some sort of trigger and the trigger we don't know exactly what it is with hiv but it could be an illness it could be aging but whatever that trigger is that is going to trigger the pro-bias pro virus to become transcriptionally active so the pro-virus will not splice out but it will become genetically active and its genes will start expressing proteins and producing the capsamers you'll start making copies of the genome and so basically it starts into biosynthesis at that point and once you've started biosynthesis which will occur in the cytoplasm then you go to maturation and then virus particles will bud off this figure is an example of life cycle of a retrovirus and again the virus is an enveloped rna virus so it will use the spikes to recognize and adhere to the appropriate host cell it will penetrate by fusion then it will go through encoding and once it goes through encoding then you have the viral rna will be reverse strand reverse transcribed into viral dna so that reverse transcriptase will form the viral dna that viral dna will get transported to the nucleus where it will fuse into the host chromosome and that forms a pro virus so that pro virus will sit there quietly for maybe the life of the cell but if there is a trigger and again we're not sure what that trigger is then this pro virus will become transcriptionally active it will start being transcribed and the genes are expressed and the cell will start producing the capsamers and copies of the genome in the cytoplasm so you get biosynthesis in the cytoplasm maturation in the cytoplasm and then released by budding one of the easiest ways to learn all the different life cycles of the animal viruses is to create a table so in the first column you can write the different stages of the viral life cycle attachment penetration biosynthesis maturation and release so these would be the first column and then you can create or add all the different types of viruses so the first one would be the outer covering the naked virus so the naked virus versus the enveloped virus naked viruses remember they use the protein fibers to recognize and attach to the appropriate host cell they penetrate by receptor mediated endocytosis and for biosynthesis you don't have any information about that if all you know is it's naked maturation you have no information and release they release by lysis the envelope virus uses the spikes they penetrate by fusion you have no information about biosynthesis or maturation and they release by budding then you have the dna viruses dna viruses it gives you no information about attachment or penetration but biosynthesis occurs in two places the genome is replicated in the nucleus and the capsule mirrors in the cytoplasm maturation will occur in the nucleus because protein can be transported into a into the nucleus dna is not transported out and release you have no information then rna viruses rna viruses again no information on attachment or penetration but all the biosynthesis occurs in the cytoplasm maturation occurs in the cytoplasm and no information about release so again if you know the outer covering and if you know the type of genome you should be able to give the full life cycle of a particular virus and the last one i talked about were the retroviruses and remember the retroviruses they are enveloped rna viruses so since they are enveloped they use this the spikes for attachment they penetrate by fusion biosynthesis occurs in the cytoplasm maturation in the cytoplasm and they release by budding but also remember after penetration you get that reverse transcriptase that makes the viral dna which splices into the chromosome and forms a pro virus which will sit in the chromosome inactive until you get a trigger once you get that trigger then that pro virus becomes transcriptionally active it's genetically activated and that will lead to biosynthesis which leads to maturation and then release when talking about viral diseases we often relate to them in three terms that describe the type of viral infections they produce and these three terms are acute chronic and latent and these are referring to two things how much virus is produced during the infection and how long the infection lasts so the first term acute refers to a very short time so this could be hours two weeks and during that short time you get a very high level of virus produced so you'll get a very high level of virus produced over a short time and some examples of this are influenza the flu and rhinovirus the common cold also another acute infection would be ebola that would also be another one a chronic virus is one that lasts for a long time so that would be months to years so a very long time and during that time you get sort of a constant low level production of virus so the individual is continually producing virus particles and that would be several types of hepatitis and human papilloma virus the last type is latent and a latent infection can last a long time but the virus production only occurs during short outbreaks so for a period of time there's absolutely no virus being produced and that is a latent infection all the herpes viruses do this so the herpes simplex 1 herpes simplex 2 and chickenpox do that because viruses are too small to be seen with the light microscope one of the ways we can identify a viral infection is by cytoplasmic effects so these are changes we can see in the host cell so for instance this is what these normal host cells look like and when you see a cell that has a different morphology that indicates a viral infection one type of cytoplasmic effect are inclusion bodies and this is where you have cells that have darker staining areas in them and that can indicate a viral infection those could be areas where biosynthesis is taking place or maturation so these are cells this is a normal cell and this is an infected cell that has all these inclusion bodies in it also there is giant cell formation giant cell formation is when many cells fuse together to form a giant cell so if this is the normal tissue often when these cells get infected with a virus they will fuse together and so what you will observe is something that looks like one giant cell with many nuclei in it and that indicates a possible viral infection a pap smear is a well-known test which is used to determine if somebody may be developing cervical cancer and what a pap smear is doing is looking for cytoplasmic effects this is an example of a normal pap smear so this is what a normal cervical cell would look like and here they're just all kind of bunched together and folded on top of each other but all these cells look normal an abnormal pap smear would have cells that look like this so that is a cytoplasmic effect where the cells have bunched up they're rounded and they no longer look like the normal cervical cells that's a cytoplasmic effect that indicates a viral infection which could lead to cancer many viruses are associated with cancer and this is the table which lists different types of viruses and relates them to the different types of cancer they are associated with probably the most famous one or most widely known one is hpv human papilloma virus which is a papova virus it's a dna virus and it is associated mainly with cervical cancer and that is why you get the hpv vaccine to hopefully prevent or reduce the chances of developing cervical cancer or any of these other cancers but there are many other viruses that are also associated with many other types of cancer and one of the things i want you to notice is that most of these viruses are dna viruses or they are retroviruses and that is very important because that relates to how they can trigger cancer to explain exactly how viruses can lead to cancer i'll actually start from the end result from cancer so i'll start at the bottom of the screen and cancer what is the basic basic definition of cancer it's basically uncontrolled cell division so what is happening is that those cells are dividing uncontrollably so they have lost control of their cell cycle so they're going through the cell cycle uncontrollably and why did this happen it happened because of a mutation so at some point in time there is a mutation in the genes that control the cell cycle and that causes the cells to lose control and divide uncontrollably in a basic definition of a mutation is a change in the dna so a change in the sequence of dna that's technically the definition of a mutation and what can some viruses do is they can splice they can splice dna into the host chromosome and when i talked about it before i talked about the viral dna from the retroviruses being able to splice into the host cell's chromosome so retro viruses are capable of doing this also not just the retroviruses but also the dna viruses so if the dna viral genome goes to the nucleus it is possible for that dna to splice into the host cells chromosome which will change the sequence of the dna in the host cell which could result in a mutation in the cell cycle genes and result in uncontrollable cell division so that is associated with retroviruses and the dna viruses because they do at some point have viral dna which can mutate the dna in the host chromosome which can lead to cancer rna viruses don't usually do this because rna cannot splice into the host chromosome so it cannot mutate the dna so it's not associated with cancer so that is why retroviruses and dna viruses are often associated with stimulating cancer the last group of microbes i want to talk about are the prions and prions are basically infectious proteins so they're not a type of cell they're not even a type of virus they're something new and all they are are proteins prions were identified first for a prisoner prusiner was doing his research in the 80s and he actually received the nobel prize in the 90s for discovering prions and prans are most famously known as the cause of mad cow disease but these prions are just proteins and so this indicates protein structure here the type of disease that prions cause are called spongy form encephalopathies so these are diseases of the brain and spinal cord and it creates holes giant holes in the brain and spinal cord so it results in the death of neurons so the type of uh side effects you see from these diseases is a loss of motor control wasting away and lots of neurological issues changes in behavior and all prion diseases are a hundred percent fatal they are also untreatable so most individuals that are diagnosed with prion disease have about a year before they die prions are relatively new microbe so we don't know a lot about them but the general hypothesis on how they damage neurons is depicted in this figure so the first thing to know or to note is that a prion is a protein and when you remember studying about proteins in a basic biology class their shape is really important to their function if you change their shape in any way you will change their function so the pathogenic prion the disease type prion has this particular shape so it has one type of shape and actually all neurons have prion proteins but they have a different shape so all of our neurons actually express prion proteins on the surface but this is the normal shape depicted by the box so when a person is exposed to a pathogenic prion so a prion protein that is folded in a different shape that prion protein is going to interact with the normally shaped prion proteins so it's going to interact with those normal prion proteins and when it does so it converts the normal prions into abnormal prions so it's kind of like a domino effect as long as you have one abnormal prion in your body that's going to start converting the other prions into abnormal prions and that continues again in a domino way or a cascade way so when a neuron has all these prions on its surface it's going to try to endocytose those prions to get rid of them so the neuron is going to perform endocytosis take them in and it's going to create these vesicles with these prion proteins in them and for whatever reason it's very difficult for the neuron to break down these prion prion proteins so what happens is the neuron starts filling up with these vesicles with the prions in them and eventually the neuron becomes so full of these vesicles with indigestible prion proteins in them that eventually the neuron dies and when the neurons start to die then you get holes in the brain prion diseases were first identified in animals and the very first animal that was identified with the disease were sheep and the disease when it's in the sheep is called scrapey and it's called scrapey because the behavior that you see in the sheep is they start rubbing against fences and trees until they start rubbing off their wool and then even they can start rubbing to the point where they start rubbing off their skin so again that's very abnormal behavior not normal behavior and the sheep can become aggressive and they also start to lose weight and again within a year of identifying scrapey and sheep they will die the second animal that has a prion disease identified are the cows and this is maybe the most famous mad cow disease and the same sort of thing the cows start to lose weight they lose coordination and they become very aggressive which is unusual for cows so that's the mad the crazy cow and again once it's identified they only survive for about a year the last animal disease is chronic wasting disease so chronic wasting disease in deer and this is actually around northern illinois southern wisconsin and during hunting season a lot of the deer are tested to see if they are carrying cwd and again you see a lot of wasting disease loss in motor control and so on prion diseases in humans there are three basic types of prion disease in humans and the first one is crutzfeld jacob and crutzefeld jacob is a spontaneous disease so when they say spontaneous what they mean is they don't know what triggered it so it seems to just spontaneously happen and of course the humans lose motor control they have psychological changes and eventually they go into basically a coma and the only way you can really diagnose this is after death when you do an autopsy and look at the brain and look at the spongy form aspect of the brain so the damage that is done but krootzville jacob is very unusual but it's spontaneous they don't know what triggers it a second type of prone disease in humans is called kuru and kuru is actually acquired so you can acquire this prion disease by eating infected nervous tissue and this was identified first in papua new guinea in new guinea they had an epidemic of kuru and what they think happened in new guinea is that one person probably developed the spontaneous kurzweil jacob disease and when that person died in these tribes in new guinea they had a funeral practice where all the family would gather and the friends would gather and they would eat a piece of the person's brain and that was their traditional funeral practice so probably what happened is the one person developed the spontaneous form kurtz fell diecum that person died the friends and family got together they ingested part of the brain and infected themselves with the prion disease and then those people died and it just propagated that way so this was a real epidemic of a prion disease and once it was figured out how it was being transmitted through the population the government outlawed that practice that funeral practice and then that stopped the epidemic so the kuru is an acquired form of a prion disease the last type of prone disease that i want to discuss is fatal familial insomnia and the important term here is familial so this is a disease that is found in families and actually this prion disease is a genetic disease so individuals actually inherit a mutated gene that will produce the prion and this gene is a dominant gene so if you have a parent who has who just displays this disease you have a 50 chance of also inheriting the g gene and if you have the gene you will develop the disease in the world there are about 30 families who have been associated with ffi and most famous family is a family in italy and it has been recorded for a couple hundred years that they have the symptoms of ffi and one of the most recent members was a man named silvano and when he first started expressing the evidence of the disease which you can kind of guess is insomnia an inability to sleep he asked the doctors to study him in hopes of finding a cure for right now there is absolutely no cure no effective treatment for any prion disease and like i mentioned before they're a hundred percent fatal