Cyanovirin-N potently inhibits human immunodeficiency virus type 1 infection in cellular and cervical explant models

Abstract

In the absence of a protective vaccine against human immunodeficiency virus (HIV), there is an urgent need for the development of effective topical microbicides to prevent HIV infection. Candidate vaginal microbicides should provide protection against circulating strains, be cheap, stable on storage, safe and easy to use. Here we describe a detailed study of the safety and efficacy of Cyanovirin-N (CV-N) in vitro, and in an ex vivo model of female genital tissue explants. CV-N demonstrated potent activity in the low nanomolar range against laboratory and primary isolates. Activity was related to the affinity of CV-N for binding to whole virions as determined by acoustic resonance. Potent activity was also observed against cell-associated HIV-1, although slightly reduced. CV-N activity in the presence of whole semen was reduced by 7-10-fold, although it remained in the low nanomolar range and was minimally modified by the presence of Candida albicans. Furthermore, CV-N potently inhibited infection of ectocervical explants and virus dissemination by tissue-emigrating cells. In peripheral blood mononuclear cell (PBMC) assays, CV-N was shown to have some mitogenic activity following 3 days exposure to compound, and this was associated with a modest increase in expression of gamma interferon, stromal cell-derived factor 1beta and interleukin 4. However, 2 h exposure to CV-N had no effect on cytokine expression in PBMC or tissue explant culture over a 24 h period, suggesting that the potential for inflammation is low. Data presented here indicate that targeting HIV envelope glycoproteins may provide an effective strategy to prevent HIV-1 infection mediated by either cell-free virus or infected cells.