Epithelial Cells in HIV Infection

N Baumgarth* (nbaumgarth@ucdavis.edu)

Center for Comparative Medicine, University of California, Davis and Dept. Stomatology, University of California, San Francisco, USA

Epithelial cells on mucosal surfaces such as the oral cavity are regarded as a barrier to HIV entry. While infection of CD4-negative epithelial cells with HIV can occur even in the absence of HIV-envelope glycoproteins in vitro, this type of infection is inefficient and in vivo might occur only rarely, if at all. However, systemic HIV infection does strongly affect the ability of mucosal surfaces to combat infections with obligate and opportunistic pathogens.  In the oral cavity this is seen in particular in the increased occurrence of lesions caused by Epstein-Barr virus, Human Papilloma virus and Candida albicans. The reasons for this increased susceptibility are only partially understood. It is possible that epithelial cells, while not directly infected, are functionally altered by the HIV-mediated alterations of the immune system. To investigate this possibility, we aimed to determine the effects of systemic HIV infection and highly-antiretroviral therapy (HAART) on oral epithelium. We performed laser-dissection microscopy-assisted gene expression studies on punch-biopsies from normal buccal mucosa of HIV-negative and HIV-infected patients with/without HAART, who were oral lesion free at the time of biopsy. Biopsy materials from HPV32-induced oral warts were also studied. Gene expression measurements were done using both a newly developed multiplex real-time RT-PCR approach, as well as comprehensive microarray analyses. Immunohistochemistry was performed on the same biopsies to assess the composition of the leukocytic infiltrate in the epithelium. The results of these studies point to subtle but distinct HIV/HAART-induced changes in the stratum spinosum of the oral mucosa. The most striking finding was the strong induction of genes associated with the Type I IFN system, potentially affecting both antigen-presentation as well as antiviral defenses. Furthermore, HIV/HAART was associated with the induction of various innate effector molecules, including multiple alpha- and beta-defensins. In contrast, the leucocytic infiltrate and other measurements related to the adaptive arm of the immune system seemed little if at all affected. It is tempting to speculate that these and other functional changes in steady-state innate immune defenses of the oral epithelium fundamentally alter the susceptibility of mucosal surfaces to insult and infection with pathogens. These studies provide a basis from which specific mechanisms affecting host-pathogen interactions can now be evaluated. This work was supported by the NIH/NIDCR grant DE-PO1-07496