Herpesvirus Saimiri Encodes a Functional Homolog of the

Here we demonstrate that open reading frame 16 (ORF16) of the oncogenic herpesvirus saimiri protects cells from heterologous virus-induced apoptosis. The BH1 and BH2 homology domains are highly conserved in ORF16, and ORF16 heterodimerizes with Bcl-2 family members Bax and Bak. However, ORF16 lacks the core sequence of the conserved BH3 homology domain, suggesting that this region is not essential for anti-apoptotic activity. Conservation of a functional bcl-2 homolog among gammaherpesviruses suggests that inhibition of programmed cell death is important in the biology of these viruses. The gammaherpesviruses have been subdivided into two genera. The prototype gamma 1 herpesvirus (lymphocryptovi-rus) is Epstein-Barr virus (EBV), a human B-cell-tropic virus that is believed to have a prominent role in the etiology of a wide variety of human malignancies (47). EBV infection of B cells in culture leads to growth transformation and the estab-lishment of a latent virus infection. Several EBV genes that are expressed during latency are required for growth transforma-tion of lymphocytes in vitro, including EBNA-LP,-2,-3A,-3C