HIV-1 and simian immunodeficiency virus (SIV), as well as their hosts, face perils at mucosal front lines in early infection. At these sites, 'resting' CD4+ memory T cells fuel infection (because they are hosts for virus), depleting CD4+ memory T cells throughout the lymphoid tissues, particularly in the gut, and eliciting an immunosuppressive regulatory T-cell response that impairs host defence. But HIV-1 and SIV also risk elimination at the earliest stage of infection, at the mucosal point of entry, if founder populations of infected cells do not expand sufficiently to establish a self-propagating infection. Microbicides and vaccines could increase these viral vulnerabilities at mucosal front lines.
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The author thanks J. Carlis, Q. Li and J. Estes for helpful discussions, C. O’Neill and T. Leonard for help with the manuscript and figures, and the National Institutes of Health (United States) for research support.