PROTECTION AGAINST APOPTOSIS BY THE VACCINIA VIRUS SPI-2 (B13R) GENE-PRODUCT

Vaccinia virus contains a gene, termed SPI-2 or B13R, that is closely related in its sequence to a potent inhibitor of apoptosis from cowpox virus (crmA). Infection by vaccinia virus protects HeLa cells against apoptosis that is induced by an immunoglobulin M antibody against the fas receptor or by tumor necrosis factor alpha. This effect is profou ndly reduced when the SPI-2 gene is deleted. The SPI-2 gene, when tran siently expressed in these cells, can also protect against apoptosis m ediated by these agents. Given the similarity to crmA, it seems likely that SPI-2 functions in an analogous fashion, inhibiting the activity of ICE protease family members and blocking the onset of apoptosis.