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

doi:10.1038/nature07831

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Glycerol monolaurate prevents mucosal SIV transmission

Journal article

Open access

Peer reviewed

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, …

Nature (London), Vol.458(7241), pp.1034-1038

04/23/2009

DOI: 10.1038/nature07831

PMCID: PMC2785041

PMID: 19262509

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Abstract

While there has been great progress in treating HIV-1 infection 1 , 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 2 – 4 . Nonetheless, studies of vaginal transmission in the SIV-rhesus macaque model point to opportunities in the earliest stages of infection where a vaccine or microbicide might be protective, by limiting the expansion of infected founder populations at the portal of entry 5 , 6 . Here we show in this SIV-macaque model, that an outside-in endocervical mucosal signalling system, involving MIP-3α, 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, recruit CD4+T cells to fuel this obligate expansion. We then show that glycerol monolaurate, a widely used antimicrobial compound 7 with inhibitory activity against production of MIP-3α and other proinflammatory cytokines 8 , can inhibit mucosal signalling and the innate and inflammatory response to HIV-1 and SIV in vitro , and in vivo can protect rhesus macaques from acute infection despite repeated intra-vaginal exposure to high doses of SIV. This novel 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 development of effective interventions to block HIV-1 mucosal transmission.

Details

Title: Subtitle: Glycerol monolaurate prevents mucosal SIV transmission
Creators: Qingsheng Li - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Jacob D Estes - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Patrick M Schlievert - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Lijie Duan - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Amanda J Brosnahan - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Peter J Southern - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Cavan S Reilly - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Marnie L Peterson - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Nancy Schultz-Darken - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Kevin G Brunner - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Karla R Nephew - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Stefan Pambuccian - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Jeffrey D Lifson - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
John V Carlis - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Ashley T Haase - Department of Computer Science and Engineering, Institute of Technology, University of Minnesota, 200 Union Street S.E., Minneapolis, Minnesota 55455, USA
Resource Type: Journal article
Publication Details: Nature (London), Vol.458(7241), pp.1034-1038
DOI: 10.1038/nature07831
PMID: 19262509
PMCID: PMC2785041
NLM abbreviation: Nature
ISSN: 0028-0836
eISSN: 1476-4687
Language: English
Date published: 04/23/2009
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984002396202771

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