The Interaction of Herpes Simplex Virus Type 1 with Cells of Neuronal Origin.

Abstract

Herpes simplex virus type 1 (HSV-1) latently infects humans, with the dormant virus being harbored in the neuronal cells. Since this implies a uniqueness about the HSV-1/neuronal cell interaction in vivo, the interaction of HSV-1 with a neuroma cell line called B103 has been examined in vitro. The B103 cells were nonpermissive for growth of HSV-1 in a multiplicity and temperature dependent fashion, with the lowest virus yields at elevated temperature and low multiplicity. When infected with active virus under those least permissive conditions, about 10% of the B103 cells survived. The survivor cells grew normally and produced no infectious virus, yet they continued to react with HSV-1 antiserum for 100 cell generations following the initial infection. To analyze the survivor cells for the presence of HSV-1 DNA, twelve cloned EcoRI restriction fragments spanning the HSV-1 genome were isolated. Using these as hybridization probes, it was found that the cells contained no newly acquired HSV-1 DNA sequences. However, they did contain cellular sequences which cross-hybridized with the HSV-1 probes. These cross-hybridizing sequences were also present in the parental B103 cell line, and in a variety of mammalian cell lines representing five species. The sequences were transcribed at an equivalent level in the B103 and survivor cells, and were derived at least in part from the 28 S ribosomal RNA genes. The degree of homology between the cellular and viral sequences, and its significance, are unknown. The reactivity of the survivor cells with HSV-1 antiserum was unrelated to these cross-hybridizing sequences, but was due to expression of a 51 kilodalton cellular protein induced during the HSV-1 infection. This protein appears to be unrelated to the p53 cellular protein induced during SV40 transformation, and it was not present in any of six HSV transformed cell lines. It was induced during lytic HSV-1 infection. No function has yet been demonstrated for the 51 kilodalton protein, and it is unknown if its expression is related to the unique ability of the B103 cells to survive infection with HSV-1.