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

Research output: Contribution to journalArticle

425 Citations (Scopus)

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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Simian Immunodeficiency Virus
HIV-1
Anti-Infective Agents
Infection
Macaca mulatta
Vaccines
Infectious Disease Transmission
Macaca
Vagina
Virus Diseases
Chemokines
Innate Immunity
Cervix Uteri
Dendritic Cells
Cytokines
T-Lymphocytes
monolaurin
Population

ASJC Scopus subject areas

  • General

Cite this

Li, Q., Estes, J. D., Schlievert, P. M., Duan, L., Brosnahan, A. J., Southern, P. J., ... Haase, A. T. (2009). Glycerol monolaurate prevents mucosal SIV transmission. Nature, 458(7241), 1034-1038. https://doi.org/10.1038/nature07831

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

In: Nature, Vol. 458, No. 7241, 23.04.2009, p. 1034-1038.

Research output: Contribution to journalArticle

Li, Q, Estes, JD, Schlievert, PM, Duan, L, Brosnahan, AJ, Southern, PJ, Reilly, CS, Peterson, ML, Schultz-Darken, N, Brunner, KG, Nephew, KR, Pambuccian, S, Lifson, JD, Carlis, JV & Haase, AT 2009, 'Glycerol monolaurate prevents mucosal SIV transmission', Nature, vol. 458, no. 7241, pp. 1034-1038. https://doi.org/10.1038/nature07831
Li Q, Estes JD, Schlievert PM, Duan L, Brosnahan AJ, Southern PJ et al. Glycerol monolaurate prevents mucosal SIV transmission. Nature. 2009 Apr 23;458(7241):1034-1038. https://doi.org/10.1038/nature07831
Li, Qingsheng ; Estes, Jacob D. ; Schlievert, Patrick M. ; Duan, Lijie ; Brosnahan, Amanda J. ; Southern, Peter J. ; Reilly, Cavan S. ; Peterson, Marnie L. ; Schultz-Darken, Nancy ; Brunner, Kevin G. ; Nephew, Karla R. ; Pambuccian, Stefan ; Lifson, Jeffrey D. ; Carlis, John V. ; Haase, Ashley T. / Glycerol monolaurate prevents mucosal SIV transmission. In: Nature. 2009 ; Vol. 458, No. 7241. pp. 1034-1038.
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