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Influenza virus

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Influenza epidemiology in humans

Fields Virology, 2nd ed, Fields & Knipe, eds, Raven Press, 1990, Fig!0"1

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Influenza mor#ali#y from 19$% #o 19%9

Fields Virology, 2nd ed, Fields & Knipe, eds, Raven Press, 1990, Fig!0"11

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#ru'#ure of influenza virus (he diagram illus#ra#es #he main s#ru'#ural fea#ures of #he virion (he surfa'e of #he par#i'le 'on#ains #hree

)inds of spi)e pro#eins* #he hemagglu#inin +-., neuraminidase +/-., and ma#ri +2. pro#ein emedded in a lipid ilayer derived from #he

hos# 'ell and 'overs #he ma#ri +1. pro#ein #ha# surrounds #he viral 'ore (he rionu'leopro#ein 'omple ma)ing up #he 'ore 'onsis#s of

a# leas# one of ea'h of #he eigh# single"s#randed R/- segmen#s asso'ia#ed 3i#h #he nu'leopro#ein +/P. and #he #hree polymerase

pro#eins +P42, P41, P-. R/- segmen#s have ase pairing e#3een #heir 56 and $6 ends forming a panhandle (heir organiza#ion and #he

role of /2 in #he virion remain unresolved +From Fields Virology, !#h ed, Knipe & o3ley, eds, 7ippin'o## 8illiams & 8il)ins, 2001, Fig

!%"2.

Influenza virus s#ru'#ure

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le'#ron mi'rographs of influenza virus -:;* (he s#ru'#ure of #he in#ernal 'omponen#s< +=. #he e#ernal vie3 - sus#an#ial fra'#ion +up #o

$0>. of influenza virions 'on#ain large heli'al in#ernal 'omponen#s +-, 4., 3hi'h may 'on#ain individual rionu'leopro#ein +R/P.

segmen#s +;. lin)ed #oge#her (he individual R/Ps ea'h 'on#ain a inding si#e for #he viral polymerase, as seen y #he immunogold

laeling of #he end of #he R/P segmen# +;. (he e#ernal vie3 of #he virions +=. illus#ra#es #he pleomorphi' appearan'e and #he surfa'e

spi)es 4ar in all figures e?uals $0 nm +From Fields Virology, !#h ed, Knipe & o3ley, eds, 7ippin'o## 8illiams & 8il)ins, 2001, Fig !%"2.

Influenza virus

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Influenza gene fun'#ions

From edi'al i'roiology, $#hed, urray, Rosen#hal & Pfaller, osy In', 200$, (ale @0"1

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- monomer i#es -" are immunodominan# epi#opes +From Fields Virology, 2nd ed, Fields & Knipe,

eds, Raven Press, 1990, Fig!0"!.

#ru'#ure of #he influenza hemagglu#inin monomer

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- #rimer +From Fields Virology, 2nd ed, Fields & Knipe, eds, Raven Press, 1990, Fig59"@.

#ru'#ure of #he influenza hemagglu#inin #rimer

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Influenza - hemagglu#inin and neuraminidase su#ypes

Fields Virology, !#h ed, Knipe & o3ley, eds, 7ippin'o## 8illiams & 8il)ins, 2001, (ale !%"1

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Influenza - reservoir

8ild a?ua#i' irds are #he main reservoir of influenza - viruses Virus #ransmission has een repor#ed from 3eild 3a#erfo3l #o poul#ry, sea

mammals, pigs, horses, and humans Viruses are also #ransmi##ed e#3een pigs and humans, and from poul#ry #o humans ?uine

influenza viruses have re'en#ly een #ransmi##ed #o dogs +From Fields Vriology +200%. $#h edi#ion, Knipe, = & o3ley, P, eds, 8ol#ers

Klu3erA7ippin'o## 8illiams & 8il)ins, Philadelphia, Fig !B1.

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Influenza repli'a#ion

Repli'a#ion of influenza - virus -f#er inding +1. #o siali' a'id"'on#aining re'ep#ors, influenza is endo'y#osed and fuses +2. 3i#h #he vesi'le

memrane Cnli)e for mos# o#her R/- viruses, #rans'rip#ion +3. and repli'a#ion +5. of #he genome o''ur in #he nu'leus Viral pro#eins are

syn#hesized +4., heli'al nu'leo'apsid segmen#s form and asso'ia#e +6. 3i#h #he 1pro#ein"lined memranes 'on#aining 2and #he - and /-

gly'opro#eins (he virus uds +7. from #he plasma memrane 3i#h 11 nu'leo'apsid segmen#s +"., /ega#ive sense< +D., posi#ive sense< R,endoplasmi' re#i'ulum +From edi'al i'roiology, $#hed, urray, Rosen#hal & Pfaller, osy In', 200$, Figure @0"2.

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i seronega#ive volun#eers re'eived 10!0 (;I=$0 of 3ild"#ype -A4e#hesdaA101$A@B virus in#ranasally on day 0 +From Fields Virology,

!#h ed, Knipe & o3ley, eds, 7ippin'o## 8illiams & 8il)ins, 2001, Fig !%"10.

Influenza pa#hogenesis in humans

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Pa#hogenesis of influenza - virus (he symp#oms of influenza are 'aused y viral pa#hologi' and immunopa#hologi' effe'#s, u# #he

infe'#ion may promo#e se'ondary a'#erial infe'#ion ;/, ;en#ral nervous sys#em +From edi'al i'roiology, $#hed, urray,

Rosen#hal & Pfaller, osy In', 200$, Figure @0"5.

Influenza pa#hogenesis

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/a#ural demons#ra#ion of reassor#men# of influenza varian#s in an in#ermedia#e hos#, 3i#h suse?uen# in#erspe'ies #ransmission - 19B0

%/% emergen# virus 3i#h high mor#ali#y for seals is 'onsis#en# 3i#h reassor#men# e#3een #3o 'on'urren#ly 'ir'ula#ing avian viruses (he

virus 'aused a 'onEun'#ivi#is in humans handling #he seals, and 'ould e eperimen#ally #ransmi##ed +assymp#oma#i'ally. #o o#her spe'ies

+From Fields Virology, 2nd ed, Fields & Knipe, eds, Raven Press, 1990, Fig!0"B.

Influenza reassor#men# in an in#ermedia#e hos#

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ene#i' reassor#men# e#3een human 1/1 and 5/5 viruses Reassor#am# viruses +R1 and R2. 'on#aining mied gene 'ons#ella#ions

3ere isola#ed from humans during 19%B and 19%9 u# no# sin'e +From Fields Virology, 2nd ed, Fields & Knipe, eds, Raven Press, 1990,

Fig!0"9.

Influenza reassor#men# in humans

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-n#igeni' drif#

-n#igeni' drif# of 5/2 viruses e#3een 19@B and 199% as demons#ra#ed y #heir 'ross"rea'#ivi#y in hemagglu#ina#ion"inhii#ion #es#s +From

Fields Virology, !#h ed, Fields & Knipe, eds, Raven Press, 1990,(ale !%"5.

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Pos#ula#ed evolu#ion of #he influenza - viruses 'urren#ly 'ir'ula#ing in humans eroar'heology sugges#s #ha# 2/2 and 5/B influenza

viruses 'ir'ula#ed in humans in 1BB9 and 1900, respe'#ively Phylogene#i' eviden'e sugges#s #ha# an influenza virus possessing eigh# gene

segmen#s from avian influenza reservoirs 3as #ransmi##ed #o humans and pigs efore 191B and repla'ed #he 1900 s#rain (his virus 3as

proaly 'arried from /or#h -meri'a #o urope y -meri'an #roops and 'aused #he 'a#as#rophi' panish influenza pandemi' of 191B In

19$% #he -sian pandemi' virus a'?uired #hree genes +P41, -, and /-. from #he avian influenza gene pool in 3ild du')s y gene#i'

reassor#men# and )ep# five o#her genes from #he 'ir'ula#ing human s#rain -f#er #he -sian s#rain appeared, #he 1/1 s#rains disappeared

from humans In 19@B #he ong Kong pandemi' virus a'?uired #3o genes +P41 and -. from #he du') reservoir y reassor#men# and )ep#

si genes from #he virus 'ir'ula#ing in humans -f#er #he appearan'e of #he ong Kong s#rain, #he 2/2 -sian s#rains 3ere no longer

de#e'#ale in humans In 19%% #he Russian 1/1 influenza virus #ha# had 'ir'ula#ed in humans in 19$0 reappeared and spread in 'hildren

and young adul#s (his virus proaly es'aped from a laora#ory and has 'on#inued #o 'o'ir'ula#e 3i#h #he 5/2 influenza viruses in #he

human popula#ion +From Fields Virology, !#h ed, Knipe & o3ley, eds, 7ippin'o## 8illiams & 8il)ins, 2001, Fig !%"1.

Influenza - evolu#ion* an#igeni' shif#

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=iagnosis, #rea#men#, va''ina#ion

G =iagnosis: ;ul#ure, hemadsor#ion, viral an#igen de#e'#ion

G (rea#men#: -man#idine and riman#idine #arge# 2

: Hanamivir and osel#amivir #arge# neuraminidaseG Va''ina#ion

: Formalin fied 3ild #ypeJ virus approved for paren#erallyadminis#ered va''ina#ion

G (rivalen#* #3o 'urren# - s#rains and one 'urren# 4 s#rain

: 7ive a##enua#ed va''ine no3 availale +Flumis#J.G (empera#ure sensi#ive re'ominan# earing relevan# - and /-

genes

: Must anticipate shift and drift in order to identify appropriatevaccine strain.

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Re'ominan# live a##enua#ed va''ine

Produ'#ion of live a##enua#ed viruses y gene#i' reassor#men# e#3een #3o influenza - viruses y #ransfer of genes from an a##enua#ed donor

virus #o a virulen# 3ild"#ype virus (he a##enua#ed reassor#an# live va''ine virus 'on#ains #he genes #ha# 'ode for #he hemagglu#inin and

neuraminidase from #he virulen# 3ild"#ype virus and #he genes #ha# 'onfer a##enua#ion from #he a##enua#ed donor virus +From Fields Vriology+200%. $#h edi#ion, Knipe, = & o3ley, P, eds, 8ol#ers Klu3erA7ippin'o## 8illiams & 8il)ins, Philadelphia, Fig !B11.

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ummary* influenza

G #ru'#ure: /ega#ive sense segmen#ed ssR/- genome, heli'al nu'leo'apsid,

enveloped

G Pa#hogenesis: respira#ory #ransmission

: repli'a#ion in nu'leus< udding: no spread +usually.: inna#e and an#iody response impor#an#< an#igeni' shif# and drif#: lo'al symp#oms from 'ell )illing< sys#emi' symp#oms from immune

response< eaggera#ed disease in young and elderly< viral and a'#erialpneumonia 'ompli'a#ions

G =iagnosis: 'ul#ure, hemadsor#ion, viral an#igen de#e'#ionG (rea#men#Apreven#ion

: aman#idine and riman#idine #arge# ma#ri< zanamivir and osel#amivir#arge# /-

: )illed and live va''ines need 'ons#an# upda#ing