Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Glycerol monolaurate prevents mucosal SIV transmission


Although there has been great progress in treating human immunodeficiency virus 1 (HIV-1) infection1, 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 transmission2,3,4. 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 entry5,6. 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 compound7 with inhibitory activity against the production of MIP-3α and other proinflammatory cytokines8—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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Mapping early expansion of infection in endocervix.
Figure 2: Influx and infection of CD4 + T cells in cervix in early infection.
Figure 3: pDCs, cytokines and chemokines associated with endocervical epithelium after exposure to SIV.
Figure 4: GML inhibits HIV-1 induced expression of MIP-3α and IL-8 in HVECs and in cervical and vaginal fluids.
Figure 5: GML prevents mucosal transmission and acute infection.


  1. 1

    Fauci, A. S. 25 years of HIV. Nature 453, 289–290 (2008)

    ADS  CAS  Article  Google Scholar 

  2. 2

    Ledford, H. HIV vaccine may raise risk. Nature 450, 325 (2007)

    ADS  CAS  Article  Google Scholar 

  3. 3

    Check, E. Scientists rethink approach to HIV gels. Nature 446, 12 (2007)

    ADS  PubMed  Google Scholar 

  4. 4

    Cohen, J. AIDS research. Microbicide fails to protect against HIV. Science 319, 1026–1027 (2008)

    CAS  Article  Google Scholar 

  5. 5

    Haase, A. T. Perils at mucosal front lines for HIV and SIV and their hosts. Nature Rev. Immunol. 5, 783–792 (2005)

    ADS  CAS  Article  Google Scholar 

  6. 6

    Miller, C. J. et al. Propagation and dissemination of infection after vaginal transmission of SIV. J. Virol. 79, 9217–9227 (2005)

    CAS  Article  Google Scholar 

  7. 7

    Kabara, J. J. in Cosmetic and Drug Preservation (eds Kabara, J. J. et al.) 305–322 (Marcel Dekker, Inc, 1984)

    Google Scholar 

  8. 8

    Peterson, M. L. & Schlievert, P. M. Glycerol monolaurate inhibits the effects of Gram-positive select agents on eukaryotic cells. Biochemistry 45, 2387–2397 (2006)

    CAS  Article  Google Scholar 

  9. 9

    Li, Q. et al. Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 434, 1148–1152 (2005)

    ADS  CAS  Article  Google Scholar 

  10. 10

    Mattapallil, J. J. et al. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434, 1093–1097 (2005)

    ADS  CAS  Article  Google Scholar 

  11. 11

    Colonna, M., Trinchieri, G. & Liu, Y. J. Plasmacytoid dendritic cells in immunity. Nature Immunol. 5, 1219–1226 (2004)

    CAS  Article  Google Scholar 

  12. 12

    Estes, J. D. et al. Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection. J. Infect. Dis. 193, 703–712 (2006)

    CAS  Article  Google Scholar 

  13. 13

    Dieu-Nosjean, M. C., Vicari, A., Lebecque, S. & Caux, C. Regulation of dendritic cell trafficking: a process that involves the participation of selective chemokines. J. Leukoc. Biol. 66, 252–262 (1999)

    CAS  Article  Google Scholar 

  14. 14

    Schlievert, P. M., Deringer, J. R., Kim, M. H., Projan, S. J. & Novick, R. P. Effect of glycerol monolaurate on bacterial growth and toxin production. Antimicrob. Agents Chemother. 36, 626–632 (1992)

    CAS  Article  Google Scholar 

  15. 15

    Narimatsu, R., Wolday, D. & Patterson, B. K. IL-8 increases transmission of HIV type 1 in cervical explant tissue. AIDS Res. Hum. Retroviruses 21, 228–233 (2005)

    CAS  Article  Google Scholar 

  16. 16

    Schlievert, P. M. et al. Glycerol monolaurate does not alter rhesus macaque (Macaca mulatta) vaginal lactobacilli and is safe for chronic use. Antimicrob. Agents Chemother. 52, 4448–4454 (2008)

    CAS  Article  Google Scholar 

  17. 17

    Crane-Godreau, M. A. & Wira, C. R. CCL20/macrophage inflammatory protein 3α and tumor necrosis factor α production by primary uterine epithelial cells in response to treatment with lipopolysaccharide or Pam3Cys. Infect. Immun. 73, 476–484 (2005)

    CAS  Article  Google Scholar 

  18. 18

    Wira, C. R., Fahey, J. V., Sentman, C. L., Pioli, P. A. & Shen, L. Innate and adaptive immunity in female genital tract: cellular responses and interactions. Immunol. Rev. 206, 306–335 (2005)

    Article  Google Scholar 

  19. 19

    Wang, Y. et al. The Toll-like receptor 7 (TLR7) agonist, imiquimod, and the TLR9 agonist, CpG ODN, induce antiviral cytokines and chemokines but do not prevent vaginal transmission of simian immunodeficiency virus when applied intravaginally to rhesus macaques. J. Virol. 79, 14355–14370 (2005)

    CAS  Article  Google Scholar 

  20. 20

    Klasse, P. J., Shattock, R. J. & Moore, J. P. Which topical microbicides for blocking HIV-1 transmission will work in the real world? PLoS Med. 3, e351 (2006)

    Article  Google Scholar 

  21. 21

    Ma, Z.-M., Abel, K., Rourke, T., Wang, Y. & Miller, C. J. A period of transient viremia and occult infection precedes persistent viremia and antiviral immune responses during multiple low-dose intravaginal simian immunodeficiency virus inoculations. J. Virol. 78, 14048–14052 (2004)

    CAS  Article  Google Scholar 

  22. 22

    Johnston, R. Microbicides 2002: an update. AIDS Patient Care STDS 16, 419–430 (2002)

    Article  Google Scholar 

  23. 23

    Shattock, R. J. & Moore, J. P. Inhibiting sexual transmission of HIV-1 infection. Nature Rev. Microbiol. 1, 25–34 (2003)

    CAS  Article  Google Scholar 

  24. 24

    Cline, A. N., Bess, J. W., Piatak, M. & Lifson, J. D. Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS. J. Med. Primatol. 34, 303–312 (2005)

    CAS  Article  Google Scholar 

  25. 25

    Peterson, M. L. et al. The innate immune system is activated by stimulation of vaginal epithelial cells with Staphylococcus aureus and toxic shock syndrome toxin 1. Infect. Immun. 73, 2164–2174 (2005)

    CAS  Article  Google Scholar 

  26. 26

    Li, Q. et al. Functional genomic analysis of the response of HIV-1 infected lymphatic tissue to antiretroviral therapy. J. Infect. Dis. 189, 572–582 (2004)

    CAS  Article  Google Scholar 

Download references


We thank C. Miller and D. Lu at the California National Primate Research Center, for helpful discussion and virus stocks, J. Kemnitz at the Wisconsin National Primate Research Center, for discussion and administrative support, and C. O’Neill and T. Leonard for help with the manuscript and figures. This work was supported in part by National Institute of Health (NIH) grants R21 AI071976 and P01 AI066314 (A.T.H.), funds from the National Cancer Institute, NIH, under contracts N01-CO-12400 and HHSN266200400088C (J.D.L.), and grant number P51 RR000167 from the National Center for Research Resources, a component of the NIH, to the Wisconsin National Primate Research Center. This research was conducted in part at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. This publication’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR or NIH.

Author information



Corresponding author

Correspondence to Ashley T. Haase.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-5 with Legends and Supplementary Tables 1-2 (PDF 913 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Li, Q., Estes, J., Schlievert, P. et al. Glycerol monolaurate prevents mucosal SIV transmission. Nature 458, 1034–1038 (2009).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing