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<title>Viruses As Agents of Disease 1</title></titleStmt>

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<date>28/04/2003</date><equipment><p>video</p></equipment>

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<u who="nm1342">the other day I was introducing # ah # the topic I was introducing epidemiology to you and I was presenting some data # about measles epidemics in the United Kingdom and and in Iceland # and I went through that rather too quickly so let's go back to it briefly # what I was saying # is that you can see # that in the united kingdom # you have these frequent epidemics # ah every # <trunc> w </trunc> well # every other year pretty well # ah between the epidemics there are still sporadic cases of measles in the country so in Britain in UK # measles is both endemic # but you get these spikes # of epidemic measles from time to time # when we look at Iceland # the picture is rather different # between epidemics # there is no # ah endemic measles at all # ah and the epidemics that occur are rather more sporadic # than you'd expect # this is the sort of data that is used # obviously to describe # ah the incidence of diseases # epidemic diseases # the difference between the United Kingdom and Iceland # really is quite simple # in Britain in the United Kingdom there is large population # in large cities # ah in Iceland the population is smaller and more dispersed # now in order for an infection to occur # there have to be susceptible individuals in that population # okay if everybody is infected and gets better # all those individuals will be resistant and so there cannot be another epidemic # there can only be another epidemic when sufficient people have been born # who are not susceptible # ooh sorry who are susceptible to the virus # that is going to happen # at a greater rate where the population is bigger # than where the population is smaller # okay # so we get these differences in behaviour # basically # quite simply because of the dynamics of population size # and the fact that individuals have to be susceptible to <trunc> ge </trunc> to be infected # okay # let's go on # and talk briefly about surveillance # i mention the term surveillance # one has to be aware # ah of the incidence of disease in a country # in order to be able to plan the medical services # and in order to be able to predict # obviously surveillance depends crucially on diagnosis # ah in the case of a disease like measles # which I've just been talking about # the diagnosis is quite simple on clinical grounds # if you have an individual # with the characteristic spots and fever of measles # then # the clinician # is quite certain # ah of his diagnosis # there are plenty of other virus infections in which the diagnosis is not so clear cut # and I'm thinking particularly of respiratory infections where you have a cold # snuffles # sneezes # and headaches or such and suchlike # this # ah these sorts of conditions can be caused by a wide range of viruses # so in order to get a reliable diagnosis # of what is the virus that's causing the current epidemic # you have to have laboratory-based # ah information # and you'll all be aware perhaps I hope # ah that in this current outbreak of <trunc> th </trunc> of SARS # the causative # virus wasn't identified immediately wasn't known # and it was only # after some work # that the virus was characterised # thus allowing one to make a definitive diagnosis of that infection # it goes without saying # that in order to be able to # ah have reliable epidemiology you have to have reliable # diagnoses # that can be clinical as in the case of measles # but quite often will require # quite detailed laboratory studies # so who is it that does this surveillance # and this is a major part of # public health service and in the united kingdom # it's done by an organisation called the Public Health # Laboratory Service # the P-H-L-S # which is # currently undergoing a very substantial reorganisation in the National Health Service # they think that reorganisation is progress I can assure it's not # if you want to look and see # what sorts of things they do # how they're organised at present # there's the website that you can go and look at # and you might find it quite interesting # obviously on a worldwide basis the organisation that is essential for surveillance # is the World Health Organisation # they do a tremendous lot of work <trunc> i </trunc> in keeping track of diseases # as for example SARS # and there is # this website that you might like to # to look at in order to find out more about what the World Health Organisation does # both of these websites are quite interesting because they work at several levels # there are some levels # which are designed for lay people # and there are other topics and areas which are designed for professionals # so you will find a wide range of information at both those sites # useful # so let me talk a little bit about the factors that ah are important in the maintenance # of a virus within a population # I've already hinted touched on one factor which is a crucial factor # which is that there have to be susceptible individuals # in the population # without susceptible individuals there is no infection # but there are obviously other factors # and probably the main factors that matter # are the efficiency of transmission # of a virus # from host to host # from the infected host # to the susceptible host # fortunately many viruses # don't easily transmit from individual to individual # ah some are very easily transmitted others are more difficult to transmit # some of the ah more # severe virus infections fortunately aren't easily transmitted and what I'm thinking about is H-I-V at the moment # you actually have to work surprisingly hard # to contract H-I-V # I don't recommend that you ah # there are other infections such as hepatitis # hepatitis B and C # ah that likewise that you have to work hard at # and apparently the current SARS virus # is much less infectious than say influenza # so that's good # influenza on the other hand is very easily transmitted from host to host # ah and so that virus # actually spreads around # much more easily # so this issue # of transmission from host to host obviously is crucial # in the # maintenance of a virus in a population # without efficient translation # the virus will die out # we're going to talk about transmission in more detail in the next lecture # the next topic #

the other factor which matters # is the survival of the virus outside the host # to pass from host to host # evidently a virus has to spend a little bit of time # in the environment # now viruses usually are rather unstable # things they tend to denature and break up very quickly and easily # ah # other viruses on the other hand really are quite stable # I'll give you some examples in a moment # so evidently if a virus is short lived in the environment # okay # the efficiency with which it transmits from one individual to another is going to be # short-lived ah is going to be low # so as I say most viruses # are actually rather unstable # in the external environment and I'm thinking of things like herpes simplex the cold sore virus and again # H-I-V # ah which has to have intimate contact for transmission # on the other hand some viruses # are remarkably stable # because they're adapted to an adverse environment # and what I'm thinking about particularly here are the so-called enteroviruses # the word enterovirus quite straight-forwardly means that these are viruses that inhabit the gut # in order to get into the gut the large bowel or whatever # those viruses have to pass through the stomach # now those of you that recollect ah # little bit of ah # practical work we did last term # remember that the stomach is actually a very acid environment # so viruses which are going to be denatured at low PH # are going to be destroyed in the stomach so enteroviruses are particularly tough # and <trunc> re </trunc> ah ah and resist # the virus # ah ah resist acid of the of the stomach # that means that they can be very stable in the environment # and if you go down # to say the River Sow just down the road # you will find lots of enteroviruses in that river # ah most of them are pretty innocuous # the <trunc> mo </trunc> most ah worrying one is polio # but fortunately it turns out always # to be the vaccine strain of polio # but the point is these viruses can survive # for a long period # in <trunc> th </trunc> the open environment # in river water # obviously # ah the exact conditions of the environment matter # for the virus survival # viruses which are transmitted by # coughs and sneezes # actually don't fly around as naked viruses # none of them do # but they are attached # or part of # the aerosol that flies out of your mouth when you cough or your nose when you sneeze # so these aerosol droplets actually keep the virus damp # wet # humid so that it doesn't denature easily # if the atmosphere is very damp # that aerosol won't evaporate very quickly # and so the virus will survive longer # if the atmosphere is very dry # on the other hand # ah the aerosol will evaporate # and the virus will denature quite quickly # that's probably why # ah some of these viruses tend to transmit better # in the winter # when we're all huddled together in warm cosy environments with high humidity and sneezing at each other #

likewise # some unstable viruses # ah may survive in specialist specialised environments # and the example which I'm suggesting here # curiously # is influenza virus # in frozen corpses at the north pole # now that might seem a rather odd # example # but it's actually fairly ah straightforward that where # exhibitions # exhibitions # expeditions # to the north pole # at the time of the great influenza pandemic of 1918 and 1919 # and there's no doubt # that this <trunc> ve </trunc> very well known # that individuals on those expeditions # suffered from influenza and died and were buried at the north pole # so their bodies were kept # in frozen conditions in deep freezers essentially because the ground is frozen at the north pole # ah and it has been shown that you can actually recover # at least fragments # of the influenza virus from that period # so there is a possibility that viruses may linger for a very long time # ah in the appropriate environments # and one of things # that archaeologists actually are actually quite concerned about is when go <trunc> a </trunc> around digging up old graveyards # is that they might uncover something # ah like smallpox # cos smallpox can survive for a long time # ah in the environment under certain circumstances # so # this whole issue of virus survival # obviously is important # in the maintenance of the virus in the population # and these other points # also plainly matter # so the amount of virus which is shed # okay # how long the infected individual is actually shedding the virus # the size of the susceptible <trunc> pop </trunc> the susceptible population I've already mentioned # and this other issue of whether there are animal reservoirs is of course tremendously important # again I've pointed out # ah that viruses may effect both humans and animals # and of course the human population may be free of the infection # but # animals # may be infected and of course the infection may spread from animals to people # so all these points # you know # these issues of stability # efficacy of transmissions # animal reservoirs # have to be taken into account by epidemiologists ah # and epidemiologists work very hard at this sort of topic because they want to develop mathematical models # which will tell them how quickly # a virus will spread through a population # what proportion of the population will be infected # I'll give you an example of that # ah it's not actually a virus # it's Creutzfeld-Jacob disease # ah human form of mad cows disease you'll know it perhaps as # ah this is another disease actually which is actually quite difficult to transmit despite all the scares that have gone about # it is not efficiently shed by populations by by infected individuals so it doesn't spread very easily amongst individuals # ah its its # i don't know it's stability in the environment is not well known # but mathematicians # have tried very hard with these with these various parameters to predict how big # ah an ah epidemic of ah new variant C-J-D might be # and they got it all wrong as you probably know # they've been predicting up to # tens of thousands of people infected with this # agent in fact it's likely to be a few dozen # but the point is # given the right information # you can model and can predict the size and extent of epidemics # which is being done right now for SARS # Okay let's leave that point now # what I've been saying is that is that the impact of viruses on society is substantial # both in mortality # certainly in the Third World still # but also through morbidity # that is the ah impact that a virus has short of lethality # okay # this is obviously the main stimulus for virology without any question # and one has to recognise that much # of the important study of viruses is actually done # at the public health level # the epidemiology level # where we're predicting patterns of disease and predicting numbers of # cases numbers of deaths or what sort of intervention will have to be carried out # okay so that brings me to the end of that topic # so I hope you all have ah the next # handout # okay # so as it were I'm now moving on # ah to talk a little bit about more detail # about how viruses move from individual to individual # and I'm going to be talking about what we call vectors # that's organisms # other ah living organisms which transmit the virus from one individual to another # and I'm also going to talk about the routes of entry into the body # okay # this is what I've just said # okay # viruses travel between one host and another either directly # or via some other agent okay # a term # I like to use quite often # in the context of virology # is natural history of infection # what this i mean what I mean by this is just sort of the broad macroscopic description of how an infection occurs # it's a useful way to take the process into its component parts and think about the individual parts of that process # so this quite simply we break down into transmission from one host to another # entry into a host # how it gets past the barriers which normally prevent a pathogen entering ah the host # then its replication within the host # how it increases its numbers # and then finally of course # the release from # that should be # the host and transmission to the next host # now what you will see # is these four steps # are essentially exactly the same four steps # as we use on the microscopic scale when we're thinking about virus infection of cells # cells have to ah the virus has to enter the cell # it replicates within the cell it's released within the cell # and passes onto the next cell so really this is the macroscopic version # of the microscopic ah cycle that you've already heard about from Andrew Easton # i can't stress this point too much that <trunc> und </trunc> understanding a virus transmission is an important step in controlling disease # I've mentioned # ah John Snow in the late 19th Century who make this connection between sewage and enteric fevers # but there are several other examples that one can think about # where understanding the transmission of a disease # has led directly # to its control # ah perhaps the most famous example is the issue # of yellow fever # a guy called Walter Reed who was an American army physician # realised ah that mosquitoes # were in some way connected with the transmission of yellow fever in the early years of the last century # the guys digging the Panama Canal # were dying like flies # perhaps that's the wrong term # of yellow fever mm # in the Canal Zone # this guy Walter Reed realised that the transmission was through mosquitoes # destroy the mosquitoes he said or more accurately destroy the places where the mosquitoes grow and you will prevent yellow fever # and that's exactly what happened # going to an example rather later in the 20th century # ah having learned # that the main transmission # of H-I-V is sexual # it's a sexually transmitted disease # if we are careful about our sexual habits # ah we will prevent the transmission of H-I-V # and I've put some question marks here # in relation to Ebola Ebola virus # I'll talk a little bit later on # some time what later on # ah is a virus which occasionally occurs in Africa # not very often fortunately because the mortality rate for this virus is about ninety percent # now the transmission of Ebola is not very well understood from one individual to another # there is probably an animal reservoir but the animal reservoir has not been identified so there's no possibility of eliminating the reservoir which was done in the case if mosquitoes and yellow fever # ah and and there is certainly person to person transmission but it's not clear how that happens # it is thought and I think there is good evidence for this # ah that the ah African funeral rites # in some ways # in some way contributes to the transmission the Africans in the parts of Africa where this disease occurs have particular rituals for washing the body of the dead # and its thought that these rituals which I don't know what they are # ah contributes to the transmission of the virus okay # so the point is perfectly plainly if you know how a virus is transmitted you can avoid it #

so # how are viruses transmitted # virologists divide the means of transmission into broad types # one is horizontal # that means basically from me to you or from you to me or from Natalie to you or whatever # that is transmission between a peer group if you like # so you can say that horizontal transmission # is any transmission from one individual to another # which is not vertical transmission # now vertical transmission # very specifically # is defined as transmission from a virus from parent # to offspring # and its almost always the mother # for obvious reasons # ah and this occurs either to the unborn child # or the newborn child # so we think of vertical transmission # as an infected mother # ah transmits the infection the virus to her child either # before birth # or after birth # so vertical transmission is a <trunc> ve </trunc> is a special case # of direct transmission from one individual to another # I'll be giving you plenty of examples as we go along # so that's direct transmission # person to person # there is indirect transmission as you will have imagined ah and this involves # vectors now i've mentioned the term vector # i'm very careful to define # what I mean by vector # in the context of virology # cos it's used in mathematics it's used in molecular biology as well # in virology we speak of vectors as a biological agent # which transmits a virus # from one host # to another # perfectly straightforward # vectors are very often arthropods # biting insects # one sort or another # okay ah # there's a number of # the more pedantic virologist perhaps I should say # ah split # the direct # horizontal transmission into into five distinct kinds <trunc> o </trunc> of route # by routes # first of all there's the airborne # that is sneezes coughs and things like that where you expel # an aerosol # and that is breathed in by somebody else # obviously # that is going to be mostly important # to the respiratory infections # or infections which involve the upper the respiratory tract which may not be # purely respiratory # also there's the so-called faecal-oral route # again that's going to be predominantly quite obviously # ah involving ah ah enteric # viruses those that replicate in the bowel # and there is transmission # via this interesting word # that I'm not quite sure how to pronounce # ah it looks like a Latin word if it was a Latin word I'd pronounce it fomites # and I've heard it pronounced fomites # and I don't know which is right # let's not worry # what it means is that viruses may be transmitted via infected material # so # let's imagine that there's somebody with ah measles # okay he has this rash # the virus is in the rash # he wipes his face with a cloth somebody else wipes <trunc> we </trunc> and so on and so forth # you can understand # how how it can be transmitted # ah a virus may be transmitted # through # materials which are actually contaminated with the virus that's fairly obvious # then we have # contact # transmission # when I say contact transmission what I mean is # more or less intimate contact between two individuals # ah ah <trunc> we </trunc> that could be handshakes # but not really what we're talking about is sexual transmission # ah that may not be # ah full-blown sexual intercourse but it could be kissing for example if you have a virus # in the saliva # or a virus in your lungs which you've coughed up # and you kiss somebody well # I'm sorry # but that's what happens # and # and there is a particular # infection which some of you will be familiar with # glandular fever # which # has also been called the course the kissing disease # because the virus which causes it # replicates very efficiently in the mouth # in the buckle cavity in the throat # so if you kiss somebody with that infection you will pick it up # okay # finally # ah we have this situation where # transmission virus may be transmitted by exchange of blood # okay # viruses can <trunc> rep </trunc> infect the whole body # that includes the blood so if you exchange blood # ah with other people and you know what I'm talking about dirty needles and all that sort of business # ah you will also # exchange any virus which is in your blood # ah you don't have to ah this doesn't have be a wicked thing ah because # some viruses in the past # well still are perhaps # transmitted by blood transfusions # ah before # ah it became clear # that there were viruses that could be transmitted in this way # I'm thinking particularly of hepatitis # ah the possibility was # that blood used for blood transfusion would be contaminated with these viruses # and so that some individual that had had his life saved # by a blood transfusion # then had his life threatened # by a severe attack of hepatitis # so <trunc> we </trunc> obviously when people knew what was happening that was stopped # right # vertical transmission # as I've said already # this can be prior to birth # now for this to happen the virus must cross the placenta # and actually # fortunately # there aren't many viruses which can do that # the one which is really prominent or used to be really prominent # in crossing the placenta and so infecting the newborn infant # ah was was rubella # German measles # and you may be <trunc> aw </trunc> are aware # that this virus if it infects the foetus causes all sorts of # developmental # problems # and so the foetus is born the child is born # ah sadly has all sorts of problems # there are other viruses which are transmitted in that way # # # # but I can't think of them # now <trunc> sh </trunc> either during birth # or shortly after birth # that's called perinatal ah infection can occur # now # I don't suppose many of you have # yet experienced childbirth ah but it's a bloody affair # # # and should the child be injured in any way during ah birth # than he's likely he or she is likely to pick up ah blood from the mother # and if that blood is contaminated well then the infection proceeds # okay # also # viruses can be in milk # # # and so an infant can be infected by the mother's milk # </u>

 

<u who="sm1343">I wonder if gametes can be</u>

 

<u who="nm1342" trans="latching">gametes no # fortunately well # gametes # if there's # there are some animal examples of viruses that can be transmitted via gametes # but not human ones # and the animal examples are some kinds of ah retrovirus # all right # but <trunc> a </trunc> <trunc> a </trunc> as in human virology # transmission by gametes doesn't happen # transmission by semen can because er # semen may be contaminated with viruses you see # ah and that potentially can infect the foetus # ah and I don't know if you been # ah if <trunc> yo </trunc> you've heard about ah a suggestion lately that # fathers can # infect # unborn children # if they're infected with H-I-V # and there's some suggestion this can be prevented by certain drug treatments # but not gametes # now the the example # two a couple of examples that I can think of # the direct transmission by blood includes # particularly herpes viruses # ah herpes simplex virus for example # the cold sore virus that occurs in a genital form as well # so if the mother is infected with ah genital herpes virus there's a chance that will be transmitted to the child during birth # the virus # which probably is # most prominently transmitted by milk is hepatitis # hepatitis B # you will be taking about <trunc> hepati </trunc> # the hepatitis viruses later # there are myriads of the darned things # but B is probably the most important one # okay so # vector transmission as i've said already # these are almost this sort of transmission is almost always # ah via arthropods # and so the term arthropod-borne and I've got it spelt right here # the arthropod viruses are sometimes contracted into arboviruses # you won't see that term very often except in medical virology because the # the real pukka card-carrying virologists # don't like this ah this term arboviruses because there are many different kinds of viruses that are transmitted by arthropods # arbovirus used to regarded as a family of viruses it plainly is not # there are many different viruses which can be transmitted by arthropod vectors # and quite often other hosts are involved here # animal reservoirs # again zoonoses # so ah going back to ah yellow fever monkeys # are a reservoir of yellow fever virus # so the virus is transmitted from the monkey reservoir # to the human # and back # by by the mosquito # so we have a very nice ah system going there # for the virus that is # just give you a few examples ah right # of arthropod viruses yellow fever I mentioned # there are many different kinds of mosquitoes # aedes is one of them # as I said the monkey is the reservoir here for yellow fever # the virus occurs basically in hot tropical countries # in Europe # ah what we have # is a virus called tick-borne encephalitis # now ticks are arthropods but they are not insects # ah and that's the particular arthropod # particular tick which transmits this virus # which causes encephalitis which is an inflammation of the brain # ah the reservoir host here # ah is rodents or birds # North-East Europe # and I have given you ah a slightly exotic one here # O'Nyong-Nyong virus # which occurs in parts of Africa # and is transmitted # by a different kind # of mosquito # anopheles mosquitoes which co-incidentally is the same kind of mosquito that transmits malaria # coincidentally # there is no known reservoir host reservoir host # for that particular virus # there are just three examples # there are many many such viruses which are transmitted by vectors # this cartoon for which I am not responsible # summarises # ah # my cartoons are much better # summarises the various points I've been making #

that's obviously a rather complicated zoonoses # ah less said about it the better # okay # so let's go on # having talked about these means of transmission in theory # <trunc> i </trunc> <trunc> i </trunc> in concept # at least # let's talk about how the virus actually gains access to its host because obviously the virus sits <trunc> o </trunc> on my skin # that's no good to the virus # it's got to get to the cells underlying my skin in order to the able replicate # so in order to initiate an infection # ah the virus must penetrate through the tissues covering the surface of the body # okay # or as i've modified it there # at least it must gain access to the cells of the surface tissues of the body in order to be able to replicate there so i'll clarify that as we go along # as you know # all # body surfaces # both internal and external # are covered by a continuous layer of epithelial cells # and these epithelial cells # overlay ah connective tissue which is muscle and such # which is sort of forms the structure of the body with the epithelium forming a lining on the top # the epithelium # epithelia rather # are distinguished into two kinds # one in which you've got many cells thick epithelium # that is spoken of as thick stratified # epithelium because there are many cells # strata # or it may be a single cell thick which is referred to as a simple epithelium # now in the stratified epithelium # the outer cells of that epithelium are cornified # that is they are basically all the ah cytoplasm is replaced by keratin # okay # now this keratin # which is the the protein of our nails and our hairs # and the surface of the skin # is a very tough protein # ah it's actually quite difficult to destroy it both physically or chemically # ah so this layer # of cornified keratinised cells # provides a very substantial horny literally # ah # barrier # physical barrier # ah to keep things out # now the sorts of # epithelia that we think of here # are obviously skin # but in general # a set of epithelia called squamous epithelia # and those include the lining of the mouth # what does it look like # ah it actually looks better on my screen than it does on that screen # just to run it through # that is the epithelium # ah # these layers of cells you can see # okay # many layers of cells # a couple of dozen # or a dozen anyway # that's the outside # can you all see my pointer # if you have a problem with my pointer tell me # can it be seen all right # my pointer # nobody says no # ah # that's the outside # and that's the inside # so this # is the junction # between the squamous epithelium # the epithelium proper # and the connective tissue underneath it # so this is your physical barrier which keeps out nasties # thick # tough # cornified # the way it works # as a tissue # now one of things we need to be aware of is many tissues the cells are replicating # constantly proliferating # dividing # and generating new cells # there are other tissues where this doesn't happen # ah the skins is one tissue where the cells constantly are proliferating # the brain the central nervous system is another tissue where they are not constantly replicating # ah proliferating # and in fact as you grow older you get less # mm # the the bottom layer # of the epithelium # is is a layer called basal layer # and the reason why it's more intensely stained # is that there is more nuclear material as as you go outwards there is less nuclear material # these are the cells that are dividing # and as they divide # they move outwards # cos you've the cells underneath pushing off # as you move outwards # they become more and more keratinised # so just here # they are # highly keratinised # and you scrape them off # you give yourself a good scrub # a good rub-down with a towel # of course you remove the outer surfaces # and they're replaced by cells growing underneath # so that's what a stratified epithelia is # or what it looks like # we'll talk about it's infection in a moment # now the point about # squamous epithelium is that it is undamaged # it is entirely impervious to viruses # but if you cut # that epithelium # or otherwise damage it # that will allow # entry potentially of the virus # through the damaged area # and of course bites # from a biting insect or tick or whatever # completely bypass this this layer # that's why arthropod vectors are so important because they # can by-pass # the physical barrier which prevents the virus infection normally # let's think about # ah right the other epithelia # the cells # of the simple epithelia # really have two main functions which you know about # absorption in the gut for example or # in the lungs absorption of oxygen # or secretion # okay # in order to do this quite obviously they cannot be cornified because if if they're thick keratin <trunc> c </trunc> nothing can go through either in or out # so almost certainly this is why our simple epithelia # are more susceptible to infection # that's why we get more respiratory and gut infections than we get skin infections # quite simple # the simple epithelia are not without # ah antiviral ah defences however # ah and we can specify really # three # these really are the same # large amounts of mucus as you know # are produced by these epithelia # the job of the mucus is to trap the viruses # and the job of the cilia is to beat the mucus out # so the virus # other pathogens is taken out with the mucus okay # but also these epithelia # ah can produce anti-viral substances # which I shall talk about more later # so these epithelia also have anti-viral defences # ah # there we go # ah the function of the mucus is to entrap the virus particles # I should say actually viruses really are present as single particles # almost always they're # in an aerosol or something like that # so we're actually talking about quite big physical particles # ah which carry the viruses okay # so we‘re not talking about a virus particle we're talking about a lump of # ah fluid # ah which has ah viruses within it # and that is what gets trapped in the mucus # and these are swept out # by the cilia # which is this is sometimes uses this is used this glorious term muco-ciliarly escalator cos it sort of # oh well let's leave that # for example particularly in the bronchi # that is the tubes going into your lungs # or alternatively of course the flow of intestinal contents in your bowel # sweeps out the virus # this # is a diagram # I'm afraid it's not a very good one # of of a cross section of of ciliated epithelium # in for example the bronchus and let's just look at it # it's the <trunc> sa </trunc> the same orientation as the picture I showed you just now the squamous epithelium # but obviously a schematic diagram it's not an actual section # couldn't find a section not one that was clear enough to illustrate these points # ah this is the epithelium # the simple epithelium # a single cell thick # with cilia so these are columnar cells celiated columnar cells # they are other cells there goblet cells # I'm not quite sure what goblet cells do # but there are also these cells here these are again epithelial cells # but they're arranged in a glandular structure # okay # so that you have these cells and their job # is obviously the secretion of mucus # which moves outwards # into this layer of mucus here # and these cilia are beating away # and pushing this either in that direction or in that direction I'm not sure which # so anything that's trapped in the mucus will move along # and be got rid of okay # this is the underlying # ah underlying connective tissue # there's some muscle there's some blood vessels or whatever # okay # it's worth mentioning as I already have mentioned that another anti-viral mechanism which is effective against enteric <trunc> we </trunc> effective against viruses that get into the that you swallow # at the low P-H so let's just think # if you inhale # virus particles # then the muco-ciliary the mucus the cilia will drive the mucus into your back of your throat # swallow it # the virus plunges down your oesophagus # into the stomach the P-H-two denatures it very nicely # unless it's an enteric virus # the more specialised immunological mechanisms I shall indeed be discussing later in some detail # okay # so the conclusion from that little topic # is that viruses have evolved many means # of gaining entry # gaining access into the host # the next step # obviously is replication within the host # for which we need to go onto the next handout # which I gave you earlier now # bear with me a moment while I load up the new one # so this next topic ah is # replication of the virus # and the spread of the virus through the body # basically the aims # okay # the aims # of this particular section of the lecture # lectures # is to describe how the viruses colonise their hosts # and how they find the sites at which they replicate # not all viruses will replicate in all cells of the body which is a good thing # some viruses will replicate only in particular tissues # so obviously have to move to those tissues # other viruses do # on the other hand replicate fairly broadly throughout the body and so again they need to disseminate which is the term which we'll define in a moment # ah # different viruses # there are basically just three broad patterns of replication within their multicellular host # first of all the obvious one is what I call localised infection # <trunc> loca </trunc> localised replication # ah that means that the virus will replicate # ah at only # the site where it first infected # it doesn't spread anywhere # so it's fairly obvious what localised means it just stays put # it replicates where it starts doesn't get any further # contrary to that # we have a situation where the infection becomes disseminated # becomes systemic # that is it spreads throughout the whole of the body # it may either be infecting and replicating in a wide range of cells # and a classic example of that is measles # measles will infect almost any cell in the body # fortunately the damage it does is not too serious # or the infection may be disseminated but there may be replication in particular target tissues # in other

words the virus tends to go # for particular tissues # particular cells # to replicate there # and broadly speaking nowhere else # or perhaps not much else # there are really three patterns # local disseminated throughout all tissues # or disseminated to a particular tissue within the body # the last example is # example of the last and a good one is of course hepatitis # but also polio virus which infects certain nervous system cells there's another example # of a virus moving through the body but targeting particular tissues # as i've just said some viruses infect a wide range of cells and so can replicate throughout the whole host # and they cause a wide range of symptoms # other viruses # ah # infect a restricted range of the cells # okay # so only certain cell types are infected # now when you think about that a little bit ah # certain <trunc> ce </trunc> cell types are restricted to certain tissues # others # ah other cell types tend to move around the body # ah and I'm thinking particularly of leucocytes # so H-I-V # infects only # well it doesn't only # but largely certain leucocytes # but these leucocytes are throughout the body # so there are sorts of # a number of sorts of nuances about what what actually can cause disseminated infections # but broadly speaking its moving around the whole body # okay # so why do virus infections show these show these different patterns # and it's actually fairly simple # they've become they are adapted # more or less to grow in different cells # and this is something called tropism with a p not to be confused with trophism # p-h # tropism means targeting particular <trunc> organis </trunc> particular things # whereas trophism # is about nutrition # so don't get trophism and tropism muddled # so obviously these viruses will only go where there cells which can replicate and they have to get there # so what are the reasons for tropism and there are several # one of the most important reasons for tropism # is # that a virus can only infect those cells that it can bind # to which it sticks # obviously we've talked about virus infections in cells # cells have to have receptors for the virus # if a cell doesn't have a receptor for a virus then the virus doesn't infect it # like day follows night # so if many different cells # have a particular <trunc> re </trunc> have a receptor for a particular virus # you get wide-scale wide ranging infection # and the example I've been using is measles # the receptor for this virus # is something called C-D-forty-six # don't worry about C-D stands for for the moment anyway # ah C-D-forty-six is a cell surface protein # which happens to be the complement receptor don't worry about that either # but the point is that this particular protein # which is the receptor for protein is present in all cells # so measles can stick to any cell # so all cells have the receptor for measles # on the other hand # if only one or a few cell types have a receptor for a particular virus # manifestly the virus infection will be restricted # and again an example that I want to mention is H-I-V # the H-I-V receptor # is another cell surface protein this time called C-D-four # i'm oversimplifying this story # so ah it's not just C-D-four but C-D-four is a major part of the receptor for this virus # and C-D-four is a protein which basically is present only on the surface of some white blood cells # that's why H-I-V only # again it's <trunc> sim </trunc> over-simplification # why H-I-V infects predominantly # certain leucocytes because they bear the receptor # for it # but receptor is not the only reason for tropism # some viruses only replicate in certain cells # irrespective # of the fact that other cells # possess the receptor # and an example of that # is human papilloma virus H-P-V ah I've forgotten to get that list of viruses # remember that I mentioned in the opening lecture that <trunc> th </trunc> I have a list of viruses which is on the website I must print it and distribute it # but it is on the website # so if you want to if you if you don't <trunc> re </trunc> write down that H-P-V stands for human papilloma virus go and look at that list of viruses and you will find H-P-V listed and called human papilloma virus # is the warts virus the virus that causes warts # this virus only replicates in squamous epithelium # we've been talking about squamous epithelium # even though it can actually bind to many other cell types # all sorts of other cells # will bind H-P-V # but it will only replicate with squamous epithelium okay # so it's not just receptors # and another example is rhino viruses # this replicates only in the upper respiratory tract # yet # even though the receptor for rhino virus is a very widely distributed self-surface protein C-D-fifty-four as it happens # okay so what I'm going to # ah start off now # is talking about a couple of examples of localised infection # one will be papilloma virus the warts virus # and the other will be rhino virus # that which causes the common cold # in the case of papilloma virus # this infects your skin as you know # and causes warts # infection of the squamous epithelium occurs only after injury for the reasons I've been giving you # the H-P-V virus # replicates first of all in the basal cells in the bottom layer # of the epithelium # these cells as I've been saying # move outwards # as the basal cells divide # and that carries the replicating virus with them # and as these cells approach # the surface of your skin # the progeny virus is produced # and is shed onto the surface of your skin # so if that if you go along and shake hands with somebody else # or do other things # ah you will transmit potentially that virus which is on your skin surface # to that other person # I will start talking about the diagrams # ah this is the same picture of the squamous epithelium that i showed you before # that with the basal cells # that red bar represents a cut and these little green thingies stars are the virus # so the virus gets in to the cut # and has access to the basal cells # it infects the basal cells remember the virus is green # it starts to replicate in the basal cells # and as they start to replicate # i'm glossing over # the actual cycle of replication # ah I'm not going to go into that detail # any detail over that # but it starts the replication is not complete at this point so there is no progeny virus being generated it's beginning but it's not yet completed # but what's happening # as i've said # is that the cells are moving outwards # as they as they proliferate # and they're carrying # the infecting virus with it # there's a lot of shuffling going on are these diagrams missing # on the next page okay right # so the infected cells are moving outwards # and finally # they get to the surface of the skin where they actually produce the progeny virus # they're not producing progeny virus down here # but up here they are # the replication cycle is completed # as the infected cell gets to the surface of the skin # so the virus is shed on the surface of the skin with the consequence of passing on the infection as I've said # okay # now I'll stop there # again tomorrow at eleven o'clock I believe # is it here again # nobody says no so I shall be here at eleven o'clock tomorrow</u> </body> </text> </TEI.2>