Murine gammaherpesvirus 68 lacking thymidine kinase shows severe attenuation of lytic cycle replication in vivo but still establishes latency.
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.
Coleman
Heather M
HM
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
de Lima
Brigitte
B
Morton
Victoria
V
Stevenson
Philip G
PG
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
D013937:Thymidine Kinase