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29 Mar 2011
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LECTUREMarch, 29th, 2011
INFLUENZA
Chinese physicians took live smallpox, scratch skin, and give it to people
Then Jenner recognized can vaccinate with something not as virulent as the actual infection
oSmallpox had high fatality rate
oSurvivors would be scarred
oMilkmaids had perfect skin, they were exposed to cowpox that didnt cause disease in
humans
oGave cowpox to a young boy, and then gave him smallpox
oWHO campaigned to eliminate smallpox
o1979 – smallpox eliminated
Polio – next campaign
oEndemic in Nigeria
oRumours that it was a US plot to sterilize Muslim men or to give AIDS
oSo people refused it
oSo cases doubled and tripled – polio started to spread again
oNow cooperation and back on track to eliminate polio
HPV vaccine
oZur Hausen – people with cervical cancer had a virus, the HPV
oVaccine to two serotypes accounts for 70% of human cancer
oNow widely used
No vaccine to HIV, malaria parasite, influenza because they are pathogens with high mutation
rates and high variability
oVaccine cannot account for the evolution of these pathogens and parasite
Influenza is todays focus
NOT stomach flu, but a respiratory illness
Influenza spread
Guinea pigs one infected at one end of chamber, uninfected at other end
oIn winter-like conditions, droplets in sneezing spread further than in summer-like
conditions
Three kinds of viruses
C – not included in any of the vaccines
Orthomyoviruses
oMany forms – pleomorphic
STRAINS
oNegative-strand RNA virus = influenza
Complimentary copy of virus in genome
Each gene on different segment
Can mix and match different segments to create new variant of virus
Two major surface proteins, H and N
Non-structuralpart of virus infectious power, but not part of structure
oH attaches to sialic acids, endocytosis
oInside endosome, pH is acidic, causing conformational change in protein to expose
fusion peptide, to lyse endosome and release viral RNA into cell
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oCopies of viral RNA packaged into new viruses, transcribed into viral proteins to
make more copies of virus
oBud out of cell to create more virus particles
oH needs to be processed – enzyme in host cell that allows cleavage of H and
maturation of virus
These enzymes limited to lung epithelial cells
Not systemic infection
Only these cells give productive infection because they cleave the H
More systemic infection – avian species, influenza is systemic infection
The enzymes required for productive infection more systemic in
avian species
Flus natural host is avian species
N allows cleave sialic acid and allow particle to leave cell to infect other cells
Enormous reservoir in the wild
Wild birds are n atural ho st
At le a st 1 6 ty p es of influenz a A in wild d u cks
At le a st 9 different ty p es of N
Often thro u g h intermediate spe cies, like pigs
oThat c a n a c c om m o d ate an avian an d tro pic virus
oBec a use of mix an d matching segments c a n
H2N2 may come b a ck into h u mans b e c a use it is com m o nly circulatin g in
Antigenic shift
Can g et re a s s ortment of RNA segments from different strains to g et n ew
Two different viruses infec ting com m on spe cies
oAs lon g as yo u g et 8 co pies of g enes, regardles s of so urc e ,
oH1N1 mix of four different strains four different viruses c a me
to g ether to give n ew combinatio n
Antigenic d rift
RNA p olymerase d o es n o t h ave pro ofr e a ding fu n ction
Viruses replic a te rapidly an d gives mistake
oAny mutatio n s that gives fu nctio n al virus c a n sele c t n ew v ariant
dru g pro blem
omust tre a t e a rly wit hin first 2 4-4 8 h o urs
ootherwise, by then h u g e p e a k in viral populatio n
omore u sed, more drug resistant
anti biotics h ave n o eff e c t
oused when p pl h ave b e c ome v ulnerable to b a c terial infe ctio n s d u e
Influenz a v a ccine co n sists of ina ctivated mixture of 3 cur r ent strains
make anti b o dies that bind to H an d prevent viral at t a c hment, preventi n g
Problem: co n tin u al mutation result s in chan g es in seq u enc e
oViral v ariant that c a n suc c e s sfully av oids n eutraliz a tio n, this is
sele c ted for an d this will replic a te
oVac cines o nly work for o n e or two se a so n s
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Document Summary

chinese physicians took live smallpox, scratch skin, and give it to people. hpv vaccine: zur hausen people with cervical cancer had a virus, the hpv, vaccine to two serotypes accounts for 70% of human cancer, now widely used. no vaccine to hiv, malaria parasite, influenza because they are pathogens with high mutation rates and high variability: vaccine cannot account for the evolution of these pathogens and parasite. not stomach flu, but a respiratory illness. guinea pigs one infected at one end of chamber, uninfected at other end: in winter-like conditions, droplets in sneezing spread further than in summer-like conditions. c not included in any of the vaccines. each gene on different segment: can mix and match different segments to create new variant of virus. two major surface proteins, h and n. these enzymes limited to lung epithelial cells. only these cells give productive infection because they cleave the h.

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