Identification of the in vivo role of a viral bcl-2.
Many gamma-herpesviruses encode candidate oncogenes including homologues of host bcl-2 and cyclin proteins (v-bcl-2, v-cyclin), but the physiologic roles of these genes during infection are not known. We show for the first time in any virus system the physiologic role of v-bcl-2. A gamma-herpesvirus v-bcl-2 was essential for efficient ex vivo reactivation from latent infection, and for both persistent replication and virulence during chronic infection of immunocompromised (interferon [IFN]-gamma(-/-)) mice. The v-cyclin was also critical for the same stages in pathogenesis. Strikingly, while the v-bcl-2 and v-cyclin were important for chronic infection, these genes were not essential for viral replication in cell culture, viral replication during acute infection in vivo, establishment of latent infection, or virulence during acute infection. We conclude that v-bcl-2 and v-cyclin have important roles during latent and persistent gamma-herpesvirus infection and that herpesviruses encode genes with specific roles during chronic infection and disease, but not acute infection and disease. As gamma-herpesviruses primarily cause human disease during chronic infection, these chronic disease genes may be important targets for therapeutic intervention.
Gangappa
Shivaprakash
S
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
van Dyk
Linda F
LF
Jewett
Travis J
TJ
Speck
Samuel H
SH
Virgin
Herbert W
HW
D000818:Animals; D002460:Cell Line; D018142:Gammaherpesvirinae / Q000235:genetics* / Q000254:growth & development* / Q000502:physiology; D019254:Genes, bcl-2; D006566:Herpesviridae Infections / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D013997:Time Factors; D014775:Virus Activation; D017735:Virus Latency
D015513:Oncogene Proteins