A potent activator of HIV-1 replication is present in the genital tract of a subset of HIV-1-infected and uninfected women

Abstract

To determine whether the female genital tract contains factors that affect HIV-1 replication. Cervicovaginal lavage (CVL) samples were collected from HIV-1-seropositive and seronegative women and added to cell cultures. HIV p24 production was used to measure the effects of CVL on replication of HIVMN in a T-cell line, of a primary isolate in peripheral blood mononuclear cells, or on HIV expression by the latently-infected monocytic U1 cell line. The effects of CVL on the HIV long terminal repeat (LTR) were determined in 1G5 T cells by measuring luciferase activity. Increased replication of HIVMN and a primary isolate were observed in T cells cultured with CVL samples from three out of 38 HIV-infected women, one out of four uninfected high-risk women, and none of 12 low-risk women. The CVL factor increased replication by enhancing virus expression via activation of the HIV LTR. The HIV-inducing activity was highly stable to heat but was sensitive to proteases, indicating that the activity was distinct from heat-labile cytokines including tumour necrosis factor-α. This is the first study to show that a factor which can stimulate HIV-1 replication is present at biologically active levels in the reproductive tract of women. This factor could potentially affect sexual or vertical transmission of HIV-1 by altering genital tract virus load or virus expression.