Glycerol monolaurate prevents mucosal SIV transmission

Qingsheng Li, Jacob D. Estes, Patrick M. Schlievert, Lijie Duan, Amanda J. Brosnahan, Peter J. Southern, Cavan S. Reilly, Marnie L. Peterson, Nancy Schultz-Darken, Kevin G. Brunner, Karla R. Nephew, Stefan Pambuccian, Jeffrey D. Lifson, John V. Carlis, Ashley T. Haase

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445 Scopus citations

Abstract

Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection, preventing transmission has thus far proven an elusive goal. Indeed, recent trials of a candidate vaccine and microbicide have been disappointing, both for want of efficacy and concerns about increased rates of transmission. Nonetheless, studies of vaginal transmission in the simian immunodeficiency virus (SIV)-rhesus macaque (Macacca mulatta) model point to opportunities at the earliest stages of infection in which a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry. Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3α (also known as CCL20), plasmacytoid dendritic cells and CCR5 + cell-attracting chemokines produced by these cells, in combination with the innate immune and inflammatory responses to infection in both cervix and vagina, recruits CD4 + T cells to fuel this obligate expansion. We then show that glycerol monolaurate'a widely used antimicrobial compound with inhibitory activity against the production of MIP-3α and other proinflammatory cytokines-can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro, and in vivo it can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This new approach, plausibly linked to interfering with innate host responses that recruit the target cells necessary to establish systemic infection, opens a promising new avenue for the development of effective interventions to block HIV-1 mucosal transmission.

Original languageEnglish (US)
Pages (from-to)1034-1038
Number of pages5
JournalNature
Volume458
Issue number7241
DOIs
StatePublished - Apr 23 2009

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    Li, Q., Estes, J. D., Schlievert, P. M., Duan, L., Brosnahan, A. J., Southern, P. J., Reilly, C. S., Peterson, M. L., Schultz-Darken, N., Brunner, K. G., Nephew, K. R., Pambuccian, S., Lifson, J. D., Carlis, J. V., & Haase, A. T. (2009). Glycerol monolaurate prevents mucosal SIV transmission. Nature, 458(7241), 1034-1038. https://doi.org/10.1038/nature07831