A HUMAN-IMMUNODEFICIENCY-VIRUS (HIV)-INDUCING FACTOR FROM THE FEMALE GENITAL-TRACT ACTIVATES HIV-1 GENE-EXPRESSION THROUGH THE KB ENHANCER

Virus-enhancing factors present in the female genital tract may influe nce the transmission of human immunodeficiency virus type 1 (HIV-1). P reviously, the presence of a heat-stable soluble factor in the cervico vaginal lavage (CVL) fluid of both HIV-infected and -uninfected women that induces HIV-1 expression in T cells and monocytes was reported. N ow this CVL factor was shown to increase HIV-1 gene expression through the activation of the kappa B enhancer in the viral long terminal rep eat (LTR). DNA binding studies, together with functional studies using mutant LTR reporter constructs, indicate the requirement for an NF-ka ppa B-dependent pathway in the CVL-mediated activation of HIV-1 expres sion. CVL samples that activated HIV-1 expression also stimulated AP-l -dependent transcription These data demonstrate that an HIV-inducing f actor, distinct from heat-labile cytokines, present in the female geni tal mucosa can activate AP-1 and NF-kappa B and increase HIV-I gene ex pression through the KB enhancer, possibly contributing to HIV-1 trans mission.