Glycerol monolaurate prevents mucosal SIV transmission

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 increas...

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Bibliographic Details
Published in:Nature 2009-04, Vol.458 (7241), p.1034-1038
Main Authors: Li, Qingsheng, Haase, Ashley T, Brunner, Kevin G, Estes, Jacob D, Lifson, Jeffrey D, Duan, Lijie, Schlievert, Patrick M, Peterson, Marnie L, Nephew, Karla R, Reilly, Cavan S, Schultz-Darken, Nancy, Pambuccian, Stefan, Southern, Peter J, Carlis, John V, Brosnahan, Amanda J
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Binomial distribution
Biological and medical sciences
Body Fluids - metabolism
Body Fluids - virology
Causes of
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - virology
Cell Cycle Proteins - metabolism
Cells
Cervix Uteri - drug effects
Cervix Uteri - immunology
Cervix Uteri - virology
Chemokine CCL20 - immunology
Chemokine CCL20 - metabolism
Dendritic Cells - immunology
Dendritic Cells - metabolism
Diagnosis
Female
Gene expression
Gene Expression Profiling
Genetic aspects
Glycerin
Glycerol
GPI-Linked Proteins
Health aspects
HIV-1 - physiology
Human immunodeficiency virus 1
Human viral diseases
Immunization
Infectious diseases
Interleukin-8 - metabolism
Laboratory animals
Laurates - pharmacology
Macaca mulatta
Macaca mulatta - virology
Mathematical models
Medical sciences
Membrane Proteins - metabolism
Monoglycerides - pharmacology
Mucous Membrane - drug effects
Mucous Membrane - immunology
Mucous Membrane - virology
Prevention
Receptors, CCR5 - immunology
Receptors, CCR5 - metabolism
RNA, Viral - blood
Sample size
Simian Acquired Immunodeficiency Syndrome - genetics
Simian Acquired Immunodeficiency Syndrome - prevention & control
Simian Acquired Immunodeficiency Syndrome - transmission
Simian Acquired Immunodeficiency Syndrome - virology
Simian immunodeficiency virus
Simian Immunodeficiency Virus - drug effects
Simian Immunodeficiency Virus - genetics
Simian Immunodeficiency Virus - growth & development
Simian Immunodeficiency Virus - physiology
Statistical methods
Time Factors
Vagina - drug effects
Vagina - virology
Viral diseases
Viral diseases of the lymphoid tissue and the blood. Aids
Virus diseases
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Summary: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-3 (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-3 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.
ISSN:0028-0836
1476-4687
1476-4679
DOI:10.1038/nature07831