title: Forced lytic replication impairs host colonization by a latency-deficient mutant of murine gammaherpesvirus-68.
abstract: A regulated switch between latent and lytic gene expression is common to all known herpesviruses. However, the effects on host colonization of altering this switch are largely unknown. We deregulated the transcription of the gene encoding the major lytic transactivator of murine gammaherpesvirus-68, ORF50, by inserting a new and powerful promoter element in its 5' untranslated region. In vitro, the mutant virus (M50) transcribed ORF50 at a high level and showed more rapid lytic spread in permissive fibroblast cultures, but in vivo, the M50 virus showed a severe deficit in latency establishment, with no sign of the infectious mononucleosis-like illness normally associated with wild-type infection. Although a low level of M50 viral DNA was detectable by PCR in spleens, replication-competent virus could not be recovered beyond 10 days post-infection. The M50 virus was also attenuated in immunocompromised mice. Thus a gammaherpesvirus unable to shut off lytic cycle gene expression showed severely restricted host colonization.
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Janet S
authors.initials: JS
authors.lastname: May
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Coleman
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Belinda
authors.initials: B
authors.lastname: Smillie
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Stacey
authors.initials: S
authors.lastname: Efstathiou
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D018142:Gammaherpesvirinae / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity* / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D041681:NIH 3T3 Cells; D016366:Open Reading Frames / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence; D014775:Virus Activation; D017735:Virus Latency / Q000235:genetics; D014779:Virus Replication
chemical_list: D014764:Viral Proteins