Replication of Herpes Simplex Virus in Human T Lymphocytes

Abstract

The replication of herpes simplex virus (HSV) in cultures of human T lymphocytes was investigated. Virus replication occurred only in lymphocyte cultures prestimulated with mitogen. At least one of the factors responsible for this phenomenon is adsorption of the virus to the cells, which was 5 times less efficient in nonstimulated cells than in stimulated cultures. Growth of virus in infected cultures was restricted to lymphocytes of T origin. This was shown by successful infection of highly purified T-cell cultures and by virus replication in four continuous T-cell lines. No virus production was obtained in cultures of lymphocytes of other than T-cell origin. Virus titers in T-lymphocyte cultures reached 10⁷ PFU/ml, which was a four logio step increase over the input dose. Lymphocytes infected with a syn strain of HSV, HSV-ANG, induced polykaryocyte formation in the cultures and therefore generated a CPE visible by microscopic examination. Infection with syn+ strains of HSV (i.e., strains which do not cause cell fusion) did not lead to such phenomena. Not more than 1% of infected T cells was replicating HSV, as revealed by infectious center assays. In contrast, about 5% of these cells showed positive immunofluorescence with anti-HSV antibodies, indicating the presence of cells which express viral protein but do not actively produce infectious virus.