HSV Type 2 Infection Increases HIV DNA Detection in Vaginal Tissue of Mice Expressing Human CD4 and CCR5

Abstract

The goal of this study was to develop an in vivo murine model that can be used to study the influence of HSV-2 on HIV infection. Mice expressing transgenes for human CD4, CCR5 and Cyclin T1 were infected intra-vaginally with HSV-2 and 3-7 days later infected with HIV. HIV DNA was detected by real time PCR. The frequency of detection of HIV DNA was significantly higher (65%) in vaginal tissue of HSV-2-infected mice compared to mock-infected mice (35%) when HIV was given 3 days after HSV-2. HSV-2 infected mice also had significantly higher levels of HIV DNA in vaginal tissue. HIV DNA was not detected in vaginal tissue of mice lacking human CD4. Longer periods (5 or 7 days) between infection with HSV-2 and HIV did not increase the frequency of detection or the amount of HIV DNA detected. HIV DNA was also detected in lymph nodes from some of the mice that were infected intra-vaginally with HSV-2 and HIV. Flow cytometric and mRNA analysis of human CD4 in vaginal tissue suggested that HSV-2 infection increased the number of T cells expressing human CD4 in vaginal tissue. This study provides evidence that HIV infection of cells occurs in the vagina of mice expressing human CD4, CCR5 and Cyclin T1 and that HSV-2 infection increases HIV infection. These findings demonstrate that this model can be used to study the mechanisms responsible for increased susceptibility to HIV in HSV-2-infected persons and for testing preventative treatments.