Maintenance of gammaherpesvirus latency requires viral cyclin in the absence of B lymphocytes.
Gammaherpesviruses establish a life-long chronic infection that is tightly controlled by the host immune response. We previously demonstrated that viruses lacking the gammaherpesvirus 68 (gammaHV68) viral cyclin (v-cyclin) exhibited a severe defect in reactivation from latency and persistent replication. In this analysis of chronic infection, we demonstrate that the v-cyclin is required for gammaHV68-associated mortality in B-cell-deficient mice. Furthermore, we identify the v-cyclin as the first gene product required for maintenance of gammaherpesvirus latency in vivo in the absence of B lymphocytes. While the v-cyclin was necessary for maintenance of latency in the absence of B cells, maintenance of v-cyclin-deficient viruses was equivalent to that of wild-type gammaHV68 in the presence of B cells. These results support a model in which maintenance of chronic gammaHV68 infection requires v-cyclin-dependent reactivation and reseeding of non-B-cell latency reservoirs in the absence of B cells and raise the possibility that B cells represent a long-lived latency reservoir maintained independently of reactivation. These results highlight distinct mechanisms for the maintenance of chronic infection in immunocompetent and B-cell-deficient mice and suggest that the different latency reservoirs have distinct gene requirements for the maintenance of latency.
van Dyk
Linda F
LF
Department of Microbiology and Immunology, University of Colorado Health Science Center, Denver 80262, USA. linda.vandyk@uchsc.edu
Virgin
Herbert W
HW
Speck
Samuel H
SH
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics; D002908:Chronic Disease; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D018142:Gammaherpesvirinae / Q000235:genetics / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000401:mortality / Q000821:virology; D016867:Immunocompromised Host; D008168:Lung / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D014764:Viral Proteins; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
D016827:CD8 Antigens; D016213:Cyclins; D014764:Viral Proteins