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Targeting early infection to prevent HIV-1 mucosal transmission

Abstract

Measures to prevent sexual mucosal transmission of human immunodeficiency virus (HIV)-1 are urgently needed to curb the growth of the acquired immunodeficiency syndrome (AIDS) pandemic and ultimately bring it to an end. Studies in animal models and acute HIV-1 infection reviewed here reveal potential viral vulnerabilities at the mucosal portal of entry in the earliest stages of infection that might be most effectively targeted by vaccines and microbicides, thereby preventing acquisition and averting systemic infection, CD4 T-cell depletion and pathologies that otherwise rapidly ensue.

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Figure 1: Time frame, sites and major events in vaginal transmission and the fast phase of lentivirus infection.
Figure 2: Ill effects of systemic infection and too little too late immune response.
Figure 3: Inflammation, innate immunity, mucosal epithelial signalling and target cell availability at mucosal front lines.

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Acknowledgements

I thank J. V. Carlis, R. P. Johnson, Q. Li, J. D. Lifson, D. Masopust, S. Pambuccian, P. J. Southern, J. Estes, D. Douek, H. W. Virgin and B. D. Walker for discussions. Errors of commission are mine as are errors of omission, with apologies to the authors of work that I could not cite because of space limitations and exclusive focus on tissue analyses. I thank C. O’Neill and T. Leonard for help with the manuscript and figures. Work from my laboratory cited in the review was supported by grants from the National Institutes of Health (AI 38565, AI 48484, AI 71976) and the International AIDS Vaccine Initiative.

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Haase, A. Targeting early infection to prevent HIV-1 mucosal transmission. Nature 464, 217–223 (2010). https://doi.org/10.1038/nature08757

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