nm1342: the other day I was introducing er ah er the topic I was introducing 
epidemiology to you and I was presenting some data er about measles epidemics 
in the United Kingdom and and in Iceland er and I went through that rather too 
quickly so let's go back to it briefly er what I was saying er is that you can 
see er that in the united kingdom er you have these frequent epidemics er ah 
every er w well er every other year pretty well er ah between the epidemics 
there are still sporadic cases of measles in the country so in Britain in UK er 
measles is both endemic er but you get these spikes er of epidemic measles from 
time to time er when we look at Iceland er the picture is rather different er 
between epidemics er there is no er ah endemic measles at all er ah and the 
epidemics that occur are rather more sporadic er than you'd expect er this is 
the sort of data that is used er obviously to describe er ah the incidence of 
diseases er epidemic diseases er the difference between the United Kingdom and 
Iceland er really is quite simple er in Britain in the United Kingdom there is 
large population er in large cities er ah in Iceland the population is smaller 
and more dispersed er now in order for an infection to occur er there have to 
be susceptible individuals in that population er okay if everybody is infected 
and gets better er all those individuals will be resistant and so there cannot 
be another epidemic er there can only be another epidemic when sufficient 
people have been born er who are not susceptible er ooh sorry who are 
susceptible to the virus er that is going to happen er at a greater rate where 
the population is bigger er than where the population is smaller er okay er so 
we get these differences in behaviour er basically er quite simply because of 
the dynamics of population size er and the fact that individuals have to be 
susceptible to ge to be infected er okay er let's go on er and talk briefly 
about surveillance er i mention the term surveillance er one has to be aware er 
ah of the incidence of disease in a country er in order to be able to plan the 
medical services er and in order to be able to predict er obviously 
surveillance depends crucially on diagnosis er ah in the case of a disease like 
measles er which I've just been talking about er the diagnosis is quite simple 
on clinical grounds er if you have an individual er with the characteristic 
spots and fever of measles er then er the clinician er is quite certain er ah 
of his diagnosis er there are plenty of other virus infections in which the 
diagnosis is not so clear cut er and I'm thinking particularly of respiratory 
infections where you have a cold er snuffles er sneezes er and headaches or 
such and suchlike er this er ah these sorts of conditions can be caused by a 
wide range of viruses er so in order to get a reliable diagnosis er of what is 
the virus that's causing the current epidemic er you have to have laboratory-
based er ah information er and you'll all be aware perhaps I hope er ah that in 
this current outbreak of th of SARS er the causative er virus wasn't identified 
immediately wasn't known er and it was only er after some work er that the 
virus was characterised er thus allowing one to make a definitive diagnosis of 
that infection er it goes without saying er that in order to be able to er ah 
have reliable epidemiology you have to have reliable er diagnoses er that can 
be clinical as in the case of measles er but quite often will require er quite 
detailed laboratory studies er so who is it that does this surveillance er and 
this is a major part of er public health service and in the united kingdom er 
it's done by an organisation called the Public Health er Laboratory Service er 
the P-H-L-S er which is er currently undergoing a very substantial 
reorganisation in the National Health Service er they think that reorganisation 
is progress I can assure it's not er if you want to look and see er what sorts 
of things they do er how they're organised at present er there's the website 
that you can go and look at er and you might find it quite interesting er 
obviously on a worldwide basis the organisation that is essential for 
surveillance er is the World Health Organisation er they do a tremendous lot of 
work i in keeping track of diseases er as for example SARS er and there is er 
this website that you might like to er to look at in order to find out more 
about what the World Health Organisation does er both of these websites are 
quite interesting because they work at several levels er there are some levels 
er which are designed for lay people er and there are other topics and areas 
which are designed for professionals er so you will find a wide range of 
information at both those sites er useful er so let me talk a little bit about 
the factors that ah are important in the maintenance er of a virus within a 
population er I've already hinted touched on one factor which is a crucial 
factor er which is that there have to be susceptible individuals er in the 
population er without susceptible individuals there is no infection er but 
there are obviously other factors er and probably the main factors that matter 
er are the efficiency of transmission er of a virus er from host to host er 
from the infected host er to the susceptible host er fortunately many viruses 
er don't easily transmit from individual to individual er ah some are very 
easily transmitted others are more difficult to transmit er some of the ah more 
er severe virus infections fortunately aren't easily transmitted and what I'm 
thinking about is H-I-V at the moment er you actually have to work surprisingly 
hard er to contract H-I-V er I don't recommend that you ah er there are other 
infections such as hepatitis er hepatitis B and C er ah that likewise that you 
have to work hard at er and apparently the current SARS virus er is much less 
infectious than say influenza er so that's good er influenza on the other hand 
is very easily transmitted from host to host er ah and so that virus er 
actually spreads around er much more easily er so this issue er of transmission 
from host to host obviously is crucial er in the er maintenance of a virus in a 
population er without efficient translation er the virus will die out er we're 
going to talk about transmission in more detail in the next lecture er the next 
topic er 
the other factor which matters er is the survival of the virus outside the host 
er to pass from host to host er evidently a virus has to spend a little bit of 
time er in the environment er now viruses usually are rather unstable er things 
they tend to denature and break up very quickly and easily er ah er other 
viruses on the other hand really are quite stable er I'll give you some 
examples in a moment er so evidently if a virus is short lived in the 
environment er okay er the efficiency with which it transmits from one 
individual to another is going to be er short-lived ah is going to be low er so 
as I say most viruses er are actually rather unstable er in the external 
environment and I'm thinking of things like herpes simplex the cold sore virus 
and again er H-I-V er ah which has to have intimate contact for transmission er 
on the other hand some viruses er are remarkably stable er because they're 
adapted to an adverse environment er and what I'm thinking about particularly 
here are the so-called enteroviruses er the word enterovirus quite straight-
forwardly means that these are viruses that inhabit the gut er in order to get 
into the gut the large bowel or whatever er those viruses have to pass through 
the stomach er now those of you that recollect ah er little bit of ah er 
practical work we did last term er remember that the stomach is actually a very 
acid environment er so viruses which are going to be denatured at low PH er are 
going to be destroyed in the stomach so enteroviruses are particularly tough er 
and re ah ah and resist er the virus er ah ah resist acid of the of the stomach 
er that means that they can be very stable in the environment er and if you go 
down er to say the River Sow just down the road er you will find lots of 
enteroviruses in that river er ah most of them are pretty innocuous er the mo 
most ah worrying one is polio er but fortunately it turns out always er to be 
the vaccine strain of polio er but the point is these viruses can survive er 
for a long period er in th the open environment er in river water er obviously 
er ah the exact conditions of the environment matter er for the virus survival 
er viruses which are transmitted by er coughs and sneezes er actually don't fly 
around as naked viruses er none of them do er but they are attached er or part 
of er the aerosol that flies out of your mouth when you cough or your nose when 
you sneeze er so these aerosol droplets actually keep the virus damp er wet er 
humid so that it doesn't denature easily er if the atmosphere is very damp er 
that aerosol won't evaporate very quickly er and so the virus will survive 
longer er if the atmosphere is very dry er on the other hand er ah the aerosol 
will evaporate er and the virus will denature quite quickly er that's probably 
why er ah some of these viruses tend to transmit better er in the winter er 
when we're all huddled together in warm cosy environments with high humidity 
and sneezing at each other er 
likewise er some unstable viruses er ah may survive in specialist specialised 
environments er and the example which I'm suggesting here er curiously er is 
influenza virus er in frozen corpses at the north pole er now that might seem a 
rather odd er example er but it's actually fairly ah straightforward that where 
er exhibitions er exhibitions er expeditions er to the north pole er at the 
time of the great influenza pandemic of 1918 and 1919 er and there's no doubt 
er that this ve very well known er that individuals on those expeditions er 
suffered from influenza and died and were buried at the north pole er so their 
bodies were kept er in frozen conditions in deep freezers essentially because 
the ground is frozen at the north pole er ah and it has been shown that you can 
actually recover er at least fragments er of the influenza virus from that 
period er so there is a possibility that viruses may linger for a very long 
time er ah in the appropriate environments er and one of things er that 
archaeologists actually are actually quite concerned about is when go a around 
digging up old graveyards er is that they might uncover something er ah like 
smallpox er cos smallpox can survive for a long time er ah in the environment 
under certain circumstances er so er this whole issue of virus survival er 
obviously is important er in the maintenance of the virus in the population er 
and these other points er also plainly matter er so the amount of virus which 
is shed er okay er how long the infected individual is actually shedding the 
virus er the size of the susceptible pop the susceptible population I've 
already mentioned er and this other issue of whether there are animal 
reservoirs is of course tremendously important er again I've pointed out er ah 
that viruses may effect both humans and animals er and of course the human 
population may be free of the infection er but er animals er may be infected 
and of course the infection may spread from animals to people er so all these 
points er you know er these issues of stability er efficacy of transmissions er 
animal reservoirs er have to be taken into account by epidemiologists ah er and 
epidemiologists work very hard at this sort of topic because they want to 
develop mathematical models er which will tell them how quickly er a virus will 
spread through a population er what proportion of the population will be 
infected er I'll give you an example of that er ah it's not actually a virus er 
it's Creutzfeld-Jacob disease er ah human form of mad cows disease you'll know 
it perhaps as er ah this is another disease actually which is actually quite 
difficult to transmit despite all the scares that have gone about er it is not 
efficiently shed by populations by by infected individuals so it doesn't spread 
very easily amongst individuals er ah its its er i don't know it's stability in 
the environment is not well known er but mathematicians er have tried very hard 
with these with these various parameters to predict how big er ah an ah 
epidemic of ah new variant C-J-D might be er and they got it all wrong as you 
probably know er they've been predicting up to er tens of thousands of people 
infected with this er agent in fact it's likely to be a few dozen er but the 
point is er given the right information er you can model and can predict the 
size and extent of epidemics er which is being done right now for SARS er Okay 
let's leave that point now er what I've been saying is that is that the impact 
of viruses on society is substantial er both in mortality er certainly in the 
Third World still er but also through morbidity er that is the ah impact that a 
virus has short of lethality er okay er this is obviously the main stimulus for 
virology without any question er and one has to recognise that much er of the 
important study of viruses is actually done er at the public health level er 
the epidemiology level er where we're predicting patterns of disease and 
predicting numbers of er cases numbers of deaths or what sort of intervention 
will have to be carried out er okay so that brings me to the end of that topic 
er so I hope you all have ah the next er handout er okay er so as it were I'm 
now moving on er ah to talk a little bit about more detail er about how viruses 
move from individual to individual er and I'm going to be talking about what we 
call vectors er that's organisms er other ah living organisms which transmit 
the virus from one individual to another er and I'm also going to talk about 
the routes of entry into the body er okay er this is what I've just said er 
okay er viruses travel between one host and another either directly er or via 
some other agent okay er a term er I like to use quite often er in the context 
of virology er is natural history of infection er what this i mean what I mean 
by this is just sort of the broad macroscopic description of how an infection 
occurs er it's a useful way to take the process into its component parts and 
think about the individual parts of that process er so this quite simply we 
break down into transmission from one host to another er entry into a host er 
how it gets past the barriers which normally prevent a pathogen entering ah the 
host er then its replication within the host er how it increases its numbers er 
and then finally of course er the release from er that should be er the host 
and transmission to the next host er now what you will see er is these four 
steps er are essentially exactly the same four steps er as we use on the 
microscopic scale when we're thinking about virus infection of cells er cells 
have to ah the virus has to enter the cell er it replicates within the cell 
it's released within the cell er and passes onto the next cell so really this 
is the macroscopic version er of the microscopic ah cycle that you've already 
heard about from Andrew Easton er i can't stress this point too much that und 
understanding a virus transmission is an important step in controlling disease 
er I've mentioned er ah John Snow in the late 19th Century who make this 
connection between sewage and enteric fevers er but there are several other 
examples that one can think about er where understanding the transmission of a 
disease er has led directly er to its control er ah perhaps the most famous 
example is the issue er of yellow fever er a guy called Walter Reed who was an 
American army physician er realised ah that mosquitoes er were in some way 
connected with the transmission of yellow fever in the early years of the last 
century er the guys digging the Panama Canal er were dying like flies er 
perhaps that's the wrong term er of yellow fever mm er in the Canal Zone er 
this guy Walter Reed realised that the transmission was through mosquitoes er 
destroy the mosquitoes he said or more accurately destroy the places where the 
mosquitoes grow and you will prevent yellow fever er and that's exactly what 
happened er going to an example rather later in the 20th century er ah having 
learned er that the main transmission er of H-I-V is sexual er it's a sexually 
transmitted disease er if we are careful about our sexual habits er ah we will 
prevent the transmission of H-I-V er and I've put some question marks here er 
in relation to Ebola Ebola virus er I'll talk a little bit later on er some 
time what later on er ah is a virus which occasionally occurs in Africa er not 
very often fortunately because the mortality rate for this virus is about 
ninety percent er now the transmission of Ebola is not very well understood 
from one individual to another er 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 er ah and and there is certainly person to person transmission but it's 
not clear how that happens er it is thought and I think there is good evidence 
for this er ah that the ah African funeral rites er in some ways er 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 er and 
its thought that these rituals which I don't know what they are er ah 
contributes to the transmission of the virus okay er so the point is perfectly 
plainly if you know how a virus is transmitted you can avoid it er 
so er how are viruses transmitted er virologists divide the means of 
transmission into broad types er one is horizontal er that means basically from 
me to you or from you to me or from Natalie to you or whatever er that is 
transmission between a peer group if you like er so you can say that horizontal 
transmission er is any transmission from one individual to another er which is 
not vertical transmission er now vertical transmission er very specifically er 
is defined as transmission from a virus from parent er to offspring er and its 
almost always the mother er for obvious reasons er ah and this occurs either to 
the unborn child er or the newborn child er so we think of vertical 
transmission er as an infected mother er ah transmits the infection the virus 
to her child either er before birth er or after birth er so vertical 
transmission is a ve is a special case er of direct transmission from one 
individual to another er I'll be giving you plenty of examples as we go along 
er so that's direct transmission er person to person er there is indirect 
transmission as you will have imagined ah and this involves er vectors now i've 
mentioned the term vector er i'm very careful to define er what I mean by 
vector er in the context of virology er cos it's used in mathematics it's used 
in molecular biology as well er in virology we speak of vectors as a biological 
agent er which transmits a virus er from one host er to another er perfectly 
straightforward er vectors are very often arthropods er biting insects er one 
sort or another er okay ah er there's a number of er the more pedantic 
virologist perhaps I should say er ah split er the direct er horizontal 
transmission into into five distinct kinds o of route er by routes er first of 
all there's the airborne er that is sneezes coughs and things like that where 
you expel er an aerosol er and that is breathed in by somebody else er 
obviously er that is going to be mostly important er to the respiratory 
infections er or infections which involve the upper the respiratory tract which 
may not be er purely respiratory er also there's the so-called faecal-oral 
route er again that's going to be predominantly quite obviously er ah involving 
ah ah enteric er viruses those that replicate in the bowel er and there is 
transmission er via this interesting word er that I'm not quite sure how to 
pronounce er ah it looks like a Latin word if it was a Latin word I'd pronounce 
it fomites er and I've heard it pronounced fomites er and I don't know which is 
right er let's not worry er what it means is that viruses may be transmitted 
via infected material er so er let's imagine that there's somebody with ah 
measles er okay he has this rash er the virus is in the rash er he wipes his 
face with a cloth somebody else wipes we and so on and so forth er you can 
understand er how how it can be transmitted er ah a virus may be transmitted er 
through er materials which are actually contaminated with the virus that's 
fairly obvious er then we have er contact er transmission er when I say contact 
transmission what I mean is er more or less intimate contact between two 
individuals er ah ah we that could be handshakes er but not really what we're 
talking about is sexual transmission er ah that may not be er ah full-blown 
sexual intercourse but it could be kissing for example if you have a virus er 
in the saliva er or a virus in your lungs which you've coughed up er and you 
kiss somebody well er I'm sorry er but that's what happens er and er and there 
is a particular er infection which some of you will be familiar with er 
glandular fever er which er has also been called the course the kissing disease 
er because the virus which causes it er replicates very efficiently in the 
mouth er in the buckle cavity in the throat er so if you kiss somebody with 
that infection you will pick it up er okay er finally er ah we have this 
situation where er transmission virus may be transmitted by exchange of blood 
er okay er viruses can rep infect the whole body er that includes the blood so 
if you exchange blood er ah with other people and you know what I'm talking 
about dirty needles and all that sort of business er ah you will also er 
exchange any virus which is in your blood er ah you don't have to ah this 
doesn't have be a wicked thing ah because er some viruses in the past er well 
still are perhaps er transmitted by blood transfusions er ah before er ah it 
became clear er that there were viruses that could be transmitted in this way 
er I'm thinking particularly of hepatitis er ah the possibility was er that 
blood used for blood transfusion would be contaminated with these viruses er 
and so that some individual that had had his life saved er by a blood 
transfusion er then had his life threatened er by a severe attack of hepatitis 
er so we obviously when people knew what was happening that was stopped er 
right er vertical transmission er as I've said already er this can be prior to 
birth er now for this to happen the virus must cross the placenta er and 
actually er fortunately er there aren't many viruses which can do that er the 
one which is really prominent or used to be really prominent er in crossing the 
placenta and so infecting the newborn infant er ah was was rubella er German 
measles er and you may be aw are aware er that this virus if it infects the 
foetus causes all sorts of er developmental er problems er and so the foetus is 
born the child is born er ah sadly has all sorts of problems er there are other 
viruses which are transmitted in that way er er er er but I can't think of them 
er now sh either during birth er or shortly after birth er that's called 
perinatal ah infection can occur er now er I don't suppose many of you have er 
yet experienced childbirth ah but it's a bloody affair er er er and should the 
child be injured in any way during ah birth er than he's likely he or she is 
likely to pick up ah blood from the mother er and if that blood is contaminated 
well then the infection proceeds er okay er also er viruses can be in milk er 
er er and so an infant can be infected by the mother's milk er 
sm1343: I wonder if gametes can be
nm1342: gametes no er fortunately well er gametes er if there's er there are 
some animal examples of viruses that can be transmitted via gametes er but not 
human ones er and the animal examples are some kinds of ah retrovirus er all 
right er but a a as in human virology er transmission by gametes doesn't happen 
er transmission by semen can because er er semen may be contaminated with 
viruses you see er ah and that potentially can infect the foetus er ah and I 
don't know if you been er ah if yo you've heard about ah a suggestion lately 
that er fathers can er infect er unborn children er if they're infected with H-
I-V er and there's some suggestion this can be prevented by certain drug 
treatments er but not gametes er now the the example er two a couple of 
examples that I can think of er the direct transmission by blood includes er 
particularly herpes viruses er ah herpes simplex virus for example er the cold 
sore virus that occurs in a genital form as well er so if the mother is 
infected with ah genital herpes virus there's a chance that will be transmitted 
to the child during birth er the virus er which probably is er most prominently 
transmitted by milk is hepatitis er hepatitis B er you will be taking about 
hepati er the hepatitis viruses later er there are myriads of the darned things 
er but B is probably the most important one er okay so er vector transmission 
as i've said already er these are almost this sort of transmission is almost 
always er ah via arthropods er and so the term arthropod-borne and I've got it 
spelt right here er the arthropod viruses are sometimes contracted into 
arboviruses er you won't see that term very often except in medical virology 
because the er the real pukka card-carrying virologists er don't like this ah 
this term arboviruses because there are many different kinds of viruses that 
are transmitted by arthropods er arbovirus used to regarded as a family of 
viruses it plainly is not er there are many different viruses which can be 
transmitted by arthropod vectors er and quite often other hosts are involved 
here er animal reservoirs er again zoonoses er so ah going back to ah yellow 
fever monkeys er are a reservoir of yellow fever virus er so the virus is 
transmitted from the monkey reservoir er to the human er and back er by by the 
mosquito er so we have a very nice ah system going there er for the virus that 
is er just give you a few examples ah right er of arthropod viruses yellow 
fever I mentioned er there are many different kinds of mosquitoes er aedes is 
one of them er as I said the monkey is the reservoir here for yellow fever er 
the virus occurs basically in hot tropical countries er in Europe er ah what we 
have er is a virus called tick-borne encephalitis er now ticks are arthropods 
but they are not insects er ah and that's the particular arthropod er 
particular tick which transmits this virus er which causes encephalitis which 
is an inflammation of the brain er ah the reservoir host here er ah is rodents 
or birds er North-East Europe er and I have given you ah a slightly exotic one 
here er O'Nyong-Nyong virus er which occurs in parts of Africa er and is 
transmitted er by a different kind er of mosquito er anopheles mosquitoes which 
co-incidentally is the same kind of mosquito that transmits malaria er 
coincidentally er there is no known reservoir host reservoir host er for that 
particular virus er there are just three examples er there are many many such 
viruses which are transmitted by vectors er this cartoon for which I am not 
responsible er summarises er ah er my cartoons are much better er summarises 
the various points I've been making er 
that's obviously a rather complicated zoonoses er ah less said about it the 
better er okay er so let's go on er having talked about these means of 
transmission in theory er i i in concept er at least er let's talk about how 
the virus actually gains access to its host because obviously the virus sits o 
on my skin er that's no good to the virus er it's got to get to the cells 
underlying my skin in order to the able replicate er so in order to initiate an 
infection er ah the virus must penetrate through the tissues covering the 
surface of the body er okay er or as i've modified it there er 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 er as you know er all er 
body surfaces er both internal and external er are covered by a continuous 
layer of epithelial cells er and these epithelial cells er overlay ah 
connective tissue which is muscle and such er which is sort of forms the 
structure of the body with the epithelium forming a lining on the top er the 
epithelium er epithelia rather er are distinguished into two kinds er one in 
which you've got many cells thick epithelium er that is spoken of as thick 
stratified er epithelium because there are many cells er strata er or it may be 
a single cell thick which is referred to as a simple epithelium er now in the 
stratified epithelium er the outer cells of that epithelium are cornified er 
that is they are basically all the ah cytoplasm is replaced by keratin er okay 
er now this keratin er which is the the protein of our nails and our hairs er 
and the surface of the skin er is a very tough protein er ah it's actually 
quite difficult to destroy it both physically or chemically er ah so this layer 
er of cornified keratinised cells er provides a very substantial horny 
literally er ah er barrier er physical barrier er ah to keep things out er now 
the sorts of er epithelia that we think of here er are obviously skin er but in 
general er a set of epithelia called squamous epithelia er and those include 
the lining of the mouth er what does it look like er ah it actually looks 
better on my screen than it does on that screen er just to run it through er 
that is the epithelium er ah er these layers of cells you can see er okay er 
many layers of cells er a couple of dozen er or a dozen anyway er that's the 
outside er can you all see my pointer er if you have a problem with my pointer 
tell me er can it be seen all right er my pointer er nobody says no er ah er 
that's the outside er and that's the inside er so this er is the junction er 
between the squamous epithelium er the epithelium proper er and the connective 
tissue underneath it er so this is your physical barrier which keeps out 
nasties er thick er tough er cornified er the way it works er as a tissue er 
now one of things we need to be aware of is many tissues the cells are 
replicating er constantly proliferating er dividing er and generating new cells 
er there are other tissues where this doesn't happen er ah the skins is one 
tissue where the cells constantly are proliferating er the brain the central 
nervous system is another tissue where they are not constantly replicating er 
ah proliferating er and in fact as you grow older you get less er mm er the the 
bottom layer er of the epithelium er is is a layer called basal layer er and 
the reason why it's more intensely stained er is that there is more nuclear 
material as as you go outwards there is less nuclear material er these are the 
cells that are dividing er and as they divide er they move outwards er cos 
you've the cells underneath pushing off er as you move outwards er they become 
more and more keratinised er so just here er they are er highly keratinised er 
and you scrape them off er you give yourself a good scrub er a good rub-down 
with a towel er of course you remove the outer surfaces er and they're replaced 
by cells growing underneath er so that's what a stratified epithelia is er or 
what it looks like er we'll talk about it's infection in a moment er now the 
point about er squamous epithelium is that it is undamaged er it is entirely 
impervious to viruses er but if you cut er that epithelium er or otherwise 
damage it er that will allow er entry potentially of the virus er through the 
damaged area er and of course bites er from a biting insect or tick or whatever 
er completely bypass this this layer er that's why arthropod vectors are so 
important because they er can by-pass er the physical barrier which prevents 
the virus infection normally er let's think about er ah right the other 
epithelia er the cells er of the simple epithelia er really have two main 
functions which you know about er absorption in the gut for example or er in 
the lungs absorption of oxygen er or secretion er okay er in order to do this 
quite obviously they cannot be cornified because if if they're thick keratin c 
nothing can go through either in or out er so almost certainly this is why our 
simple epithelia er are more susceptible to infection er that's why we get more 
respiratory and gut infections than we get skin infections er quite simple er 
the simple epithelia are not without er ah antiviral ah defences however er ah 
and we can specify really er three er these really are the same er large 
amounts of mucus as you know er are produced by these epithelia er the job of 
the mucus is to trap the viruses er and the job of the cilia is to beat the 
mucus out er so the virus er other pathogens is taken out with the mucus okay 
er but also these epithelia er ah can produce anti-viral substances er which I 
shall talk about more later er so these epithelia also have anti-viral defences 
er ah er there we go er ah the function of the mucus is to entrap the virus 
particles er I should say actually viruses really are present as single 
particles er almost always they're er in an aerosol or something like that er 
so we're actually talking about quite big physical particles er ah which carry 
the viruses okay er so we‘re not talking about a virus particle we're talking 
about a lump of er ah fluid er ah which has ah viruses within it er and that is 
what gets trapped in the mucus er and these are swept out er by the cilia er 
which is this is sometimes uses this is used this glorious term muco-ciliarly 
escalator cos it sort of er oh well let's leave that er for example 
particularly in the bronchi er that is the tubes going into your lungs er or 
alternatively of course the flow of intestinal contents in your bowel er sweeps 
out the virus er this er is a diagram er I'm afraid it's not a very good one er 
of of a cross section of of ciliated epithelium er in for example the bronchus 
and let's just look at it er it's the sa the same orientation as the picture I 
showed you just now the squamous epithelium er but obviously a schematic 
diagram it's not an actual section er couldn't find a section not one that was 
clear enough to illustrate these points er ah this is the epithelium er the 
simple epithelium er a single cell thick er with cilia so these are columnar 
cells celiated columnar cells er they are other cells there goblet cells er I'm 
not quite sure what goblet cells do er but there are also these cells here 
these are again epithelial cells er but they're arranged in a glandular 
structure er okay er so that you have these cells and their job er is obviously 
the secretion of mucus er which moves outwards er into this layer of mucus here 
er and these cilia are beating away er and pushing this either in that 
direction or in that direction I'm not sure which er so anything that's trapped 
in the mucus will move along er and be got rid of okay er this is the 
underlying er ah underlying connective tissue er there's some muscle there's 
some blood vessels or whatever er okay er it's worth mentioning as I already 
have mentioned that another anti-viral mechanism which is effective against 
enteric we effective against viruses that get into the that you swallow er at 
the low P-H so let's just think er if you inhale er virus particles er then the 
muco-ciliary the mucus the cilia will drive the mucus into your back of your 
throat er swallow it er the virus plunges down your oesophagus er into the 
stomach the P-H-two denatures it very nicely er unless it's an enteric virus er 
the more specialised immunological mechanisms I shall indeed be discussing 
later in some detail er okay er so the conclusion from that little topic er is 
that viruses have evolved many means er of gaining entry er gaining access into 
the host er the next step er obviously is replication within the host er for 
which we need to go onto the next handout er which I gave you earlier now er 
bear with me a moment while I load up the new one er so this next topic ah is 
er replication of the virus er and the spread of the virus through the body er 
basically the aims er okay er the aims er of this particular section of the 
lecture er lectures er is to describe how the viruses colonise their hosts er 
and how they find the sites at which they replicate er not all viruses will 
replicate in all cells of the body which is a good thing er some viruses will 
replicate only in particular tissues er so obviously have to move to those 
tissues er other viruses do er 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 er ah er different viruses er there are 
basically just three broad patterns of replication within their multicellular 
host er first of all the obvious one is what I call localised infection er loca 
localised replication er ah that means that the virus will replicate er ah at 
only er the site where it first infected er it doesn't spread anywhere er so 
it's fairly obvious what localised means it just stays put er it replicates 
where it starts doesn't get any further er contrary to that er we have a 
situation where the infection becomes disseminated er becomes systemic er that 
is it spreads throughout the whole of the body er it may either be infecting 
and replicating in a wide range of cells er and a classic example of that is 
measles er measles will infect almost any cell in the body er fortunately the 
damage it does is not too serious er or the infection may be disseminated but 
there may be replication in particular target tissues er in other 
words the virus tends to go er for particular tissues er particular cells er to 
replicate there er and broadly speaking nowhere else er or perhaps not much 
else er there are really three patterns er local disseminated throughout all 
tissues er or disseminated to a particular tissue within the body er the last 
example is er example of the last and a good one is of course hepatitis er but 
also polio virus which infects certain nervous system cells there's another 
example er of a virus moving through the body but targeting particular tissues 
er as i've just said some viruses infect a wide range of cells and so can 
replicate throughout the whole host er and they cause a wide range of symptoms 
er other viruses er ah er infect a restricted range of the cells er okay er so 
only certain cell types are infected er now when you think about that a little 
bit ah er certain ce cell types are restricted to certain tissues er others er 
ah other cell types tend to move around the body er ah and I'm thinking 
particularly of leucocytes er so H-I-V er infects only er well it doesn't only 
er but largely certain leucocytes er but these leucocytes are throughout the 
body er so there are sorts of er a number of sorts of nuances about what what 
actually can cause disseminated infections er but broadly speaking its moving 
around the whole body er okay er so why do virus infections show these show 
these different patterns er and it's actually fairly simple er they've become 
they are adapted er more or less to grow in different cells er and this is 
something called tropism with a p not to be confused with trophism er p-h er 
tropism means targeting particular organis particular things er whereas 
trophism er is about nutrition er so don't get trophism and tropism muddled er 
so obviously these viruses will only go where there cells which can replicate 
and they have to get there er so what are the reasons for tropism and there are 
several er one of the most important reasons for tropism er is er that a virus 
can only infect those cells that it can bind er to which it sticks er obviously 
we've talked about virus infections in cells er cells have to have receptors 
for the virus er if a cell doesn't have a receptor for a virus then the virus 
doesn't infect it er like day follows night er so if many different cells er 
have a particular re have a receptor for a particular virus er you get wide-
scale wide ranging infection er and the example I've been using is measles er 
the receptor for this virus er is something called C-D-forty-six er don't worry 
about C-D stands for for the moment anyway er ah C-D-forty-six is a cell 
surface protein er which happens to be the complement receptor don't worry 
about that either er but the point is that this particular protein er which is 
the receptor for protein is present in all cells er so measles can stick to any 
cell er so all cells have the receptor for measles er on the other hand er if 
only one or a few cell types have a receptor for a particular virus er 
manifestly the virus infection will be restricted er and again an example that 
I want to mention is H-I-V er the H-I-V receptor er is another cell surface 
protein this time called C-D-four er i'm oversimplifying this story er so ah 
it's not just C-D-four but C-D-four is a major part of the receptor for this 
virus er and C-D-four is a protein which basically is present only on the 
surface of some white blood cells er that's why H-I-V only er again it's sim 
over-simplification er why H-I-V infects predominantly er certain leucocytes 
because they bear the receptor er for it er but receptor is not the only reason 
for tropism er some viruses only replicate in certain cells er irrespective er 
of the fact that other cells er possess the receptor er and an example of that 
er is human papilloma virus H-P-V ah I've forgotten to get that list of viruses 
er remember that I mentioned in the opening lecture that th I have a list of 
viruses which is on the website I must print it and distribute it er but it is 
on the website er so if you want to if you if you don't re 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 er is the warts virus 
the virus that causes warts er this virus only replicates in squamous 
epithelium er we've been talking about squamous epithelium er even though it 
can actually bind to many other cell types er all sorts of other cells er will 
bind H-P-V er but it will only replicate with squamous epithelium okay er so 
it's not just receptors er and another example is rhino viruses er this 
replicates only in the upper respiratory tract er yet er even though the 
receptor for rhino virus is a very widely distributed self-surface protein C-D-
fifty-four as it happens er okay so what I'm going to er ah start off now er is 
talking about a couple of examples of localised infection er one will be 
papilloma virus the warts virus er and the other will be rhino virus er that 
which causes the common cold er in the case of papilloma virus er this infects 
your skin as you know er and causes warts er infection of the squamous 
epithelium occurs only after injury for the reasons I've been giving you er the 
H-P-V virus er replicates first of all in the basal cells in the bottom layer 
er of the epithelium er these cells as I've been saying er move outwards er as 
the basal cells divide er and that carries the replicating virus with them er 
and as these cells approach er the surface of your skin er the progeny virus is 
produced er and is shed onto the surface of your skin er so if that if you go 
along and shake hands with somebody else er or do other things er ah you will 
transmit potentially that virus which is on your skin surface er to that other 
person er I will start talking about the diagrams er ah this is the same 
picture of the squamous epithelium that i showed you before er that with the 
basal cells er that red bar represents a cut and these little green thingies 
stars are the virus er so the virus gets in to the cut er and has access to the 
basal cells er it infects the basal cells remember the virus is green er it 
starts to replicate in the basal cells er and as they start to replicate er i'm 
glossing over er the actual cycle of replication er ah I'm not going to go into 
that detail er any detail over that er 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 er but what's happening er as i've said er 
is that the cells are moving outwards er as they as they proliferate er and 
they're carrying er the infecting virus with it er there's a lot of shuffling 
going on are these diagrams missing er on the next page okay right er so the 
infected cells are moving outwards er and finally er they get to the surface of 
the skin where they actually produce the progeny virus er they're not producing 
progeny virus down here er but up here they are er the replication cycle is 
completed er as the infected cell gets to the surface of the skin er so the 
virus is shed on the surface of the skin with the consequence of passing on the 
infection as I've said er okay er now I'll stop there er again tomorrow at 
eleven o'clock I believe er is it here again er nobody says no so I shall be 
here at eleven o'clock tomorrow