A POTENT ACTIVATOR OF HIV-1 REPLICATION IS PRESENT IN THE GENITAL-TRACT OF A SUBSET OF HIV-1-INFECTED AND UNINFECTED WOMEN

Objective and design: To determine whether the female genital tract co ntains factors that affect HIV-1 replication. Cervicovaginal lavage (C VL) samples were collected from HIV-1-seropositive and seronegative wo men and added to cell cultures. Methods: HIV p24 production was used t o 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 effec ts of CVL on the HIV long terminal repeat (LTR) were determined in 1G5 T cells by measuring luciferase activity. Results: Increased replicat ion of HIVMN and a primary isolate were observed in T cells cultured w ith CVL samples from three out of 38 HIV-infected women, one out of fo ur uninfected high-risk women, and none of 12 low-risk women. The CVL factor increased replication by enhancing virus expression via activat ion of the HIV LTR. The HIV-inducing activity was highly stable to hea t but was sensitive to proteases, indicating that the activity was dis tinct from heat-labile cytokines including tumour necrosis factor-alph a. Conclusions: This is the first study to show that a factor which ca n stimulate HIV-1 replication is present at biologically active levels in the reproductive tract of women. This factor could potentially aff ect sexual or vertical transmission of HIV-1 by altering genital tract virus load or virus expression.