CoronavirusesChapter 40Structure and CompositionEnvelopedSpike proteins resemble solar corona or crown120-160 nm Positive-strand !" #2$-%2 kb&C'toplasmic replication(uddin) into E and *ol)i!otoriousl' di+cult to propa)ate in culture,i)h -re.uenc' o- recombinationCause colds and severe acute respirator' s'ndrome #S"S&Classi/cation0amil' Coronaviridae*enus Coronavirus*enus Toroviruseplication1etails are lar)el' unknown because viruses are di+cult to )row in cell culture2ouse hepatitis virus is model -or coronavirus replication3iral spike proteins mediate attachment"minopeptidase ! is a cell receptor tar)et -or man' coronavirusesEndoc'tosis is thou)ht to mediate in-ection"-ter uncoatin)4 the viral )enome #m!"& is translated to produce !" pol'meraseSub)enomic !"s are s'nthesi5ed -or each viral pol'peptide*enomic !" is cos'nthesi5ed with nucleocapsidesults in nucleocapsid bindin) immediatel' to )enomic !"Pro)en' virus buds -rom E and *ol)i and are packa)ed into vesicles 3esicles travel to and -use with plasma membrane4 releasin) viral particles -rom cellCoronavirus 6n-ectionsPatho)enesis7imited knowled)e,i)hl' species-speci/c8'picall' mild upper respirator' in-ections #9colds:& that remain locali5edE;ception< S"S6mmunit' is not durable2an' people become resusceptible a-ter a -ew 'ears7aborator' 1ia)nosisE76S" - ma' not discriminate past in-ections,"PC3irus isolation is di+cult #o-ten impossible& and re.uires )reat e;pertiseSevere "cute espirator' S'ndrome6nitial outbreak in SE "sia,on) =on) and Sin)apore /rst reported1isease ori)inated in China>ri)inall' thou)ht to be -rom wild )ame marketsPalm civet cat #which isn?t a cat& - Paradoxurus hermaphroditusaccoon do) #which isn?t a do)& - Nyctereutes procyonoides6t is a bat virusChinese horseshoe bats #Rhinolophus sinicus&!o virus isolation"mpli/cation o- coronavirus !" -rom anal swabsSerolo)'6t is hi)hl'-similar4 but not identical to S"S-Co32utations have most likel' occurred in transmission -rom bats to civets to humanseverse )enetics o- S"S-Co3 and some bat viruses has been done!o animal patho)enesis modelS"S Co3Coronavirus Ph'lo)en'Ch'motr'psin-like protease #%C7pro&4 !"-dependent !" pol'merase #Pol&4 spike #S&4 and nucleocapsid #!& Coronaviruses "re (at 3irusesS"S Patho)enesis3irus is transmitted b' respirator' and -ecal routes6n-ection is mediated b' human an)iotensin-convertin) en5'me 2 #h"CE2& receptor,i)h e;pression7un) alveolar epithelial cells6ntestinal enteroc'tes7ow e;pression(lood vessels #virtuall' all or)ans&PneumoniaCause o- death is lun) -ailurePulmonar' 6n@ammation o- S"SPatholo)ic /ndin)s o- lun) tissue sectionsA "< Pulmonar' con)estion and edema #,BE stain4 ori)inal ma)ni/cation ;100&A (< " mild de)ree o- interstitial l'mphoc'tic in/ltrationA 6ntra-alveolar or)ani5in) e;udative lesion was occasionall' -oundA 1etached at'pical pneumoc'tes indicated b' arrow #,BE stain4 ori)inal ma)ni/cation ;200&A C< "t'pical multinucleated pneumoc'tes were occasionall' identi/edA 1e/nite viral inclusion was not apparent #,BE stain4 ori)inal ma)ni/cation ;400&A 1< 0ibrin thrombi were -re.uentl' noted in small pulmonar' arteries and arterioles #,BE stain4 ori)inal ma)ni/cation ;200&A6s S"S an 6mmunopatho)enesisCCriterion Evidence in S"S Precedent in other viral in-ectionsDorse disease with decrease in viral loadControversialE viral titres4 measured in nasophar'n)eal-aspirate samples4 decrease as clinical disease worsensE but hi)h viral loads have been detected in lun)s and immune cells a-ter death2,3-induced dem'elination increases as virus is clearedE 2,3-%-induced hepatitis correlates with macropha)e activation and not viral loadE and 6(3-induced nephritis is detected in chickens with ver' low viral loads2acropha)e or 1C in-ection6n-ection is abortive but induces e;pression o- pro-in@ammator' mediators2,3 and 06P3 productivel' in-ect macropha)es2acropha)e in/ltration into sites o- in@ammation2acropha)es are present in lar)e numbers in in-ected lun)s6n 2,3 in-ection4 macropha)es in/ltrate the C!S coincident with dem'elination #thou)ht to be the /nal eFector cell&E and in 06P3 in-ection4 macropha)es are the main cell t'pe in )ranulomas and are crucial -or patho)enesis,i)h concentration o- pro-in@ammator' mediators in serum or at site o- in-ectionControversialE anti-in@ammator' mediators mi)ht contribute to dela'ed viral clearance2,3-%-induced 0*72 e;pression is crucial -or liver necrosisE in 2,3-G,2-in-ected mice4 60!- is re.uired -or C1HI 8-cell-mediated responsesE and in 06P3 in-ection4 increased c'tokine concentrations are present in blood and tissues durin) e;acerbation o- disease6nhibition o- t'pe 6 60! induction in in-ected cellsShown usin) isolated macropha)es4 1Cs and /broblasts2,3 does not induce t'pe 6 60! e;pression7'mphopenia and neutrophiliaPresent in most severe casesE and l'mphoc'tic in-ection has been detected6n 06P3 in-ection4 l'mphopaenia is present durin) clinical relapsesE and in 2,3-% in-ection4 l'mphopaenia is present and l'mphoc'tic in-ection has been detected,aemopha)oc'tosis Present in severe cases !ot reported