Bovine herpesvirus 1 U(S) ORF8 protein induces apoptosis in infected cells and facilitates virus egress.

The bovine herpesvirus 1 (BHV-1) U(S) ORF8 protein with homology to the Us9 protein of other alphaherpesviruses induces apoptosis in rabbit kidney (RK13) cells without the presence of other BHV-1-encoded proteins. In this article, we have characterized the cytotoxicity and growth behavior of a BHV-1 recombinant, BHV-1/D8, which fails to express the U(S) ORF8 protein in infected cells. BHV-1/D8 exhibited a reduced cytotoxicity to RK13 cells when compared to the cytotoxicity of control BHV-1 strains. In RK13 cells, the onset of apoptosis was not observed during the infection with BHV-1/D8, and the virus multiplication of BHV-1/D8 was markedly greater than that of control viruses. However, virus release of progeny viruses from the infected RK13 cells into culture supernatant was significantly decreased by the loss of the U(S) ORF8 protein. These data demonstrate that the U(S) ORF8 protein activates the apoptotic process and facilitates virus release from the BHV-1-infected cells.