Effects of human papillomavirus-associated cells on human immunodeficiencyvirus gene expression

Objective: To examine the effects of soluble factors secreted by human papi llomavirus (HPV)-associated cells on human immunodeficiency virus (HIV) exp ression. Methods: Supernatants collected from cultured cervical biopsies and cervica l cancer cell lines, and HPV-immortalized and normal keratinocytes were tes ted for the ability to induce HIV p24 production in two cell lines that con tained latent HIV (the U1 monocytic line and the ACH-2 T cell line). Levels of HIV p24 were measured by enzyme-linked immunosorbent assay (ELISA). Cul ture supernatants were also assayed for the inflammatory cytokines interleu kin 6, tumor necrosis factor, and interleukin 1 beta by ELISA. Results: Supernatants from all epithelial cells tested upregulated HIV p24 expression in the U1 line but not in the ACH-2 cells. Only differentiated n ormal keratinocytes induced p24 production by ACH-2 cells. Neutralization o f the cytokines, particularly interleukin 6, partially reduced the level of HIV-inducing activity in the culture supernatants. Additionally, cervical biopsies from HIV-infected women cultured in vitro also were able to induce HIV in U1 cells but not ACH-2 cells. Conclusions: Our results suggest that HPV infection of the cervix might inf luence HIV pathogenesis by inducing the production of immune and inflammato ry factors that enhance HIV expression. (Obstet Gynecol 2000;96:879-85. (C) 2000 by The American College of Obstetricians and Gynecologists.).