Herpes simplex virus type 1 induces apoptosis in peripheral blood T lymphocytes

Apoptosis in peripheral blood T lymphocytes induced by herpes simplex virus type 1 (HSV-1) was investigated by use of DNA content analysis and the terminal deoxytransferase-mediated dUTP nick end-labeling method. The hypodiploid fraction in the cell cycle and DNA fragmentation were both increased in HSV-1-infected T lymphocytes compared with that in mock-infected T lymphocytes on stimulation with phytohemagglutinin (PHA). There was no difference in the hypodiploid fraction and DNA fragmentation between HSV-1-infected T lymphocytes and mock-infected cells cultured without PHA. HSV-1 enhanced apoptosis in CD4 and HLA-DR-positive T lymphocytes, but not in CD8 lymphocytes, when stimulated with PHA. These results demonstrate that HSV-1 infection enhances apoptosis in activated T lymphocytes, particularly CD4 and HLA-DR-positive T lymphocytes. bcl-2 expression was unchanged in mock- and HSV-1-infected CD4 and CD8 lymphocytes cultured with or without PHA, indicating that bcl-2 does not contribute to HSV-1-induced apoptotic cell death. Apoptosis in CD4 helper T lymphocytes may account for immunosuppression and lymphocytopenia following HSV-1 infection.