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

Gregory T. Spear, Lena Al-Harthi, Beverly Sha, Mary Nel Saarloos, Mary Hayden, L. Stewart Massad, Constance Benson, Kenneth A. Roebuck, Nancy R. Glick, Alan Landay

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Objective and design: 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. Methods: HIV p24 production was used to measure the effects of CVL on replication of HIV(MN) 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. Results: Increased replication of HIV(MN) 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)1319-1326
Number of pages8
JournalAIDS
Volume11
Issue number11
DOIs
StatePublished - Oct 15 1997
Externally publishedYes

Keywords

  • Activation
  • Cellular factors/cytokines
  • Sexual transmission
  • Vertical transmission
  • Virus replication

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