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Paramyxoviruses

Measles, mumps,

parainfuenza virus,respiratory syncytial virus,human metapneumovirus

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Human pathogens in the orderMononegavirales

Family Subfamily Genus Human pathogensRhabdoviridae

Lyssavirus Rabies virus

Filoviridae

Marburghvirus Marburgh virus

Ebolavirus Ebola virusParamyxoviridae

Paramyxovirinae

Rubulavirus Mumps virus, Parainfluenzavirus 2,4

Respirovirus Parainfluenza virus 1,3

Henipavirus Hendra virus, Nipah virus

Morbillivirus Measles virus

Pneumovirinae

Pneumovirus Respirator s n! tial virus

Metaneumovirus Human metapneumovirus

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Mononegavirales genomestructure

N P M F H/HN/G L3" #"

N P M G L3" #"

Paramyxoviridae

Rhabdoviridae

Notes!"HN # mumps, P$%& H # measles& G # '(% ,hMP%, ra)ies*"'a)ies lac+s F

"P encodes *- proteins in Paramyxovirinae .P/%/ "4)Rubula- , Pneumo- , and Metapneumo- contain extra genes .M*, (H0"F 1 G s2itched in Pneumoviruses

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Mononegavirales gene3unction

Gene product Virion location Function

Nucleoprotein .N orNP"

Nucleocapsid Protects 'N4 genome

Polymerasephosphoprotein .P"

4ssociated 2ithnucleocapsid

'N4 polymerasesu)unit

Matrix .M" 5et2eennucleocapsid andenvelope

%irion assem)ly

Fusion 3actor .F" 6ransmem)raneenvelope glycoprotein

Fusion and entry

Hemagglutinin-neuraminidase .HN"&hemagglutinin .H"&glycoprotein .G"

6ransmem)raneenvelope glycoprotein

%iral attachmentprotein

Large protein .L" 4ssociated 2ithnucleocapsid

'N4 polymerase

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Paramyxoviridae structure

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Paramyxovirus structure

Paramyxovirus electronmicrograph

http0 eb(u!t(a!(za depts mmi stannard param (html

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Mononegavirales replication

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Measles induced syncytia

$ormation of giant !ells s n! tia5 in measles pneumonia( Noti!e the eosinophili! in!lusions in both the ! toplasm and nu!lei( $rom

%!hae!hter"s Me!hanisms of Mi!robial &isease' 4 th ed(' Engleberg, &iRita ) &ermod ' *ippin!ott, +illiams ) +il ins' 2--.' $ig( 34/35

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Measles general6 7ne o3 the 8ve classical childhood exanthems

.eruptive diseases 7 ru)ella .togavirus" 7 roseola .HH% 9"

7 83th disease .parvovirus, 5!:, erythema in3ectiosum" 7 chic+enpox .herpes zoster"6 7ne o3 the most prominent causes o3 disease in

unvaccinated populations 7 ;-

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Measles pathogenesis

Me!hanisms of spread of themeasles virus ithin the bodand the pathogenesis ofmeasles( 8M9, 8ell/mediatedimmunit ' 8N%, !entralnervous s stem( $romMedi!al Mi!robiolog , # th ed(,Murra , Rosenthal ) Pfaller,Mosb 9n!(, 2--#, $ig( #:/3(5

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Measles time course

;ime !ourse of measles virus infe!tion(8hara!teristi! prodrome s mptoms are!ough, !ons spots and rash(%%PE, %uba!ute s!lerosing

panen!ephalitis( $rom Medi!alMi!robiolog , # th ed(, Murra , Rosenthal )Pfaller, Mosb 9n!(, 2--#, $ig( #:/4(5

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>opli+?s spots

=opli >s spots in the mouth ande anthem( =opli >s spots usuallpre!ede the measles rash andma be seen for the first da ort o after the rash appears(

8ourtes &r( ?(9( Pugh, %t( @lbans'from Emond R;&, Ro land H@=0

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Measles rash

Measles rash( $rom Habif ;P0 linicaldermatology! olor guide to diagnosis andtherapy, %t *ouis, 1:A#, Mosb (5 $rom Medi!alMi!robiolog , # th ed(, Murra , Rosenthal ) Pfaller,Mosb 9n!(, 2--#, $ig( #:/B(5

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Measles pathogenesis

Me!hanisms of spread of themeasles virus ithin the bodand the pathogenesis ofmeasles( 8M9, 8ell/mediated

immunit ' 8N%, !entralnervous s stem( $romMedi!al Mi!robiolog , # th ed(,Murra , Rosenthal ) Pfaller,Mosb 9n!(, 2--#, $ig( #:/3(5

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Measles vaccination

Reported !ases of measles in the Cnited %tates, 1:#-01::-( 9mmediatel after the introdu!tion of the va!!ine, the in!iden!e de!lineddramati!all ( @ measles epidemi! o!!urred bet een 1:A: and 1::1, ith most !ases affe!t ing unva!!inated !hildren ounger than # ears(

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Mumps

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Mumps pathogenesis

Me!hanism of spread of mumps virus ithin the bod ( $rom Medi!al Mi!robiolog , # th ed(, Murra , Rosenthal ) Pfaller, Mosb 9n!(, 2--#, $ig(#:/.(5

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Mumps time course

;ime !ourse of mumps virusinfe!tion( $rom Medi!alMi!robiolog , # th ed(, Murra ,Rosenthal ) Pfaller, Mosb 9n!(,2--#, $ig( #:/A(5

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Mumps symptoms

8hild ith parotitis( $rom $ields Driolog 2--.5 #th edition, =nipe, &M ) Ho le , PM, eds, +olters =lu er *ippin!ott+illiams ) +il ins, Philadelphia $ig( 43(4

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'espiratory syncytial virus

6 @idespread A0B o3 in3ants seropositive )y ! year o3 age6 Cearly in =( 0;,;;;-D;,;;; hospitilizations, !;; in3ant deaths, !A,;;; elderlydeaths

6 Host range limited to humans& single serotype6 'espiratory transmission

7 Highly contageous& contagion period precedes symptoms and may occur in a)sence o3symptoms

6 Localized in3ections o3 respiratory tract, no viremia and no systemic in3ections

6 Eisease 7 hildren ! y o )ronchiolitis 7 Pneumonia 7 ommon cold in older children and adults

6 Poor immunity 7 'ein3ection occurs thoughout li3e 7 Maternal anti)ody does not prevent in3ection

6 Eiagnosis

7 rtP ', immunofuorescence, enzyme immunoassay, serology6 6reatment 7 'i)avarin reduces severity o3 symptoms in immunocomprimized patients

6 No vaccine& improper vaccination increases severity o3 disease6 Passive vacciniation 3or high ris+ in3ants

7 Palivizuma) anti-F monoclonal anti)ody

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Parainfuenza viruses6 Four serotypes, host range limited to humans,6 'espiratory transmission6 $n3ections limited to respiratory tract, generally non-

systemic and viremia rare6 auses cold-li+e symptoms, )ronchitis and croup .serotypes

! and *" $n3ections o3 children common6 Eiagnosis

7 %irus culture 7 (yncytia 3ormation 7 Hemadsorption 7 Hemagglutination inhi)ition 7 rtP '

6 $mmunity 3ollo2ing in3ection short-lived $ndividuals su) ectto re-in3ection

6 andidate vaccines are in various stages o3 clinical trials

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Human metapneumovirus

6 'espiratory transmission6 Eisease asymptomatic, common

cold, )ronchiolotis, pheumonia 7 4ccounts 3or !0B o3 common colds in

children

6 Eiagnosis )y rtP '

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Paramyxovirus summary6 (tructure

7 Negative sense ss'N4 genome, helical nucleocapsid, envelope2ith attachment protein and F protein6 Pathogenesis

7 6ransmission in respiratory droplets and 3usion o3 virusenvelope via F protein 2ith plasma mem)rane o3 cells in therespiratory tract

7 'eplication in cytoplasm, )udding 7 %iremia except 3or '(% and P$% 7 $nnate and anti)ody response important& many symptoms 3rom

immune response rash in measles and s2elling in mumps& P$%)ronchitis and croup& '(% )ronchiolitis and pneumonia inin3ants

7 (eIuelae in N( 3or measles and mumps6 Eiagnosis

7 (erology or nucleic acid 7 Measles >opli+ spots& mumps s2elling o3 parotid gland

6 6reatment/prevention 7 MM' live attenuated viral vaccine 3or measles and mumps,

none 3or '(% or P$%