Multiple Viral CoreProteins AreDeterminants of Reovirus-Induced AcuteMyocarditis

Previously, we showedthattheMI gene (encoding a viral core protein, ,I2, whosefunction isunknown)was associated withtheefficiently myocarditic phenotype ofa reovirus variant, 8B.Here,we haveextended our genetic analysis of8Bandconducted genetic analysesoftwootherreovirus strains (TIL[serotype 1 strain Lang]andAbney). Ourresults demonstrate thatmultiple viral core proteins are determinants ofreovirusinduced myocarditis. Incontrast toour previous association of,u2 withinduction ofmyocarditis, thisprovides strong evidence that a corefunction achieved through theinteraction ofmultiple core proteins isresponsible forinduction ofthedisease. Muchevidence overtheyearssuggests that awiderange of viruses areasignificant causeofhumanmyocarditis (24, 27,38, 48). We arestudying reovirus-induced murinemyocarditis to identify theviral genesthat determine theacutedisease andto examine themechanism bywhichthevirus damages cardiac tissue. We haveshownthatefficiently myocarditic andpoorly myocarditic reovirus strains replicate tosimilar titers inthe heart (42, 44); thus, differences inmyocarditic potential donot simply reflect growth intheheart. Inprimary cell cultures, the induction ofcytopathic effect incardiac myocytes, butnot cardiac fibroblasts, iscorrelated withinduction ofmyocarditis (3). Finally, cell-mediated immunity isimportant inprotecting against theacutedisease (43), whichisconsistent withthe proposed mechanism forcoxsackievirus-induced acutemyocarditis (15), andincontrast tothesuggested damaging role for immunecomponents incoxsackievirus-induced