The sexually transmitted viral infections HIV and Herpes simplex virus (HSV) encounter epithelial dendritic cells immediately after transmission, Langerhan cells in stratified squamous epithelium and also for HIV lamina propria Dendritic cells (DCs) in cuboidal/columnar epithelium. HSV-2 and HIV have opposite effects on model DCs. HIV is noncytopathic and induces maturation of DCs for transfer to its major targets, T lymphocytes. HSV induces apoptosis of DCs (including Langerhan cells) which can then be taken up by neighbouring DCs. Recent work from our laboratory shows that in human foreskin explants Herpes simplex virus infects Langerhan cells and then, after LC migration, is transferred to two different types of dermal DCs, probably as intact infectious virus. In isolated culture HSV infected apoptopic Langerhan cells are also readily taken up by the dermal DCs, indicating a cell-virus ‘relay’ which eventually stimulates CD4 and CD8 lymphocytes after dermal DC migration to lymph nodes, explaining similar findings in murine models.
We have previously shown that HIV induces maturation of DCs and that this occurs via a combined effect of the virus and accompanying microvesicles in the inoculum derived from infected T cells. These microvesicles contain >200 proteins of which only Heat shock protein 90 and HIV nef are able to induce such maturation. We have now shown that these microvesicles and their active molecules are able to induce an early spike of cytokines, likely have biological effects on surrounding T cells. Furthermore the interaction between HSV and HIV during co-infection of DCs/LCs results in enhanced HIV production. HSV infection stimulates TNFα production which enhances the HIV receptor CCR5 on neighbouring uninfected DCs. This interaction may contribute to the well described enhanced acquisition of HIV by subjects who are previously infected with HSV-2.