title: Murine gammaherpesvirus 68 lacking thymidine kinase shows severe attenuation of lytic cycle replication in vivo but still establishes latency.
abstract: The lytic cycle functions of gammaherpesviruses have received relatively little attention to date, at least in part due to the lack of a convenient experimental model. The murine gammaherpesvirus 68 (MHV-68) now provides such a model and allows the roles of individual lytic cycle gammaherpesvirus proteins to be evaluated in vivo. We have used MHV-68 to determine the contribution of a gammaherpesvirus thymidine kinase (TK) to viral lytic replication and latency establishment. MHV-68 mutants with a disrupted TK gene grew normally in vitro but showed a severe attenuation of replication in the lungs after intranasal inoculation, with lytic titers at least 1,000-fold lower than those of wild-type and revertant viruses. Nevertheless, the establishment of latency by the TK-deficient mutants, while delayed, was not prevented by their lytic replication deficit. The viral TK clearly plays a crucial role in the capacity of MHV-68 to replicate efficiently in its natural host but does not seem to be essential to establish a persistent infection. The potential of TK-deficient mutants as gammaherpesvirus vaccines is discussed.
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Coleman
authors.forename: Brigitte
authors.initials: B
authors.lastname: de Lima
authors.forename: Victoria
authors.initials: V
authors.lastname: Morton
authors.forename: Philip G
authors.initials: PG
authors.lastname: Stevenson
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D018142:Gammaherpesvirinae / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D013937:Thymidine Kinase / Q000172:deficiency* / Q000235:genetics; D014774:Virulence; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D013937:Thymidine Kinase