Immunosuppression of mice by cyclophosphamide (CyP) and cyclosporin A (CsA) changes the course of HSV-1 infection and the distribution of viral DNA in target organs.

The effects of the immunosuppressive drugs cyclophosphamide (CyP), cyclosporin A (CsA) and the Langerhans cells immunomodulator OK-432, a bacterial cell wall preparation, on herpes simplex virus type-1 (HSV-1) infection in mice were studied. An increased mortality of HSV-1-infected mice was observed following intraperitoneal injection of both the pathogenic HSV-1 (Justin) and the apathogenic UL56-deleted HSV-1-M-LacZ strains. Intraperitoneal injection of CyP prior to infection with HSV-1 increased the susceptibility to infection of normally resistant mouse strains, including the inbred strain C57BL/6 and the outbred Sabra strain, with the virus reaching the pancreas, the spinal cord and the spleen. Polymerase chain reaction (PCR) to detect viral DNA in mouse organs following IP HSV-1 injection after treatment with CyP and/or OK-432 showed that CyP treatment prevented the virus from reaching the pancreas, while a combination treatment of both chemicals allowed HSV-1 to reach the pancreas. These studies indicate that treatment of mice with immunosuppressive drugs (CyP and CsA), which affect dendritic cells and T cells, prevents the migration of HSV-1 to the pancreas, while the immunomodulator OK-432, which induces dendritic cell activity, did not prevent virus migration to the pancreas. Lung samples were consistently positive for viral DNA following treatment with either CyP or CsA. PCR to detect viral DNA in mice injected with HSV-1 via the footpad route following pretreatment with CyP and OK-432 also through the footpad revealed the presence of HSV-1 DNA in the spinal cord on days 1, 3, and 5 post-infection.(ABSTRACT TRUNCATED AT 250 WORDS)