Divergent Molecular Pathways ofProductive andLatentInfection witha Virulent Strain ofHerpesSimplex VirusType1

Mutants ofherpes simplex virus (HSV)havebeenusedtoshowthat a variety ofkeygenesassociated with initiation oflytic infection or replication ofviral DNA are notessential forestablishment oflatency. These observations areextended inthepresent study, inwhich avirulent strain ofHSVtype1thatisnotcompromised initsability toproductively infect neurons underfavorable conditions was usedtodemonstrate early divergence ofmolecular pathways leading toproductive andlatent infection. Ourexperimental strategy made unique useofthesegmental innervation ofthevertebrate trunktostudy thespread ofvirus throughout the peripheral nervoussystem after inoculation ofmouse flanks. Evidence ofviral geneexpression, including that ofimmediate-early genes,was transient, confined toganglia directly innervating theinoculated skin(8th through 12ththoracic segments), andseenonlyatsites fromwhichinfectious virus couldberecovered. In contrast, neuronscontaining latency-associated transcripts andreactivatable virus were more widely distrib