title: Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract.
abstract: Worldwide, HIV-1 infects millions of people annually, the majority of whom are women. To establish infection in the female reproductive tract (FRT), HIV-1 in male ejaculate must overcome numerous innate and adaptive immune factors, traverse the genital epithelium, and establish infection in underlying CD4(+) target cells. How the virus achieves this remains poorly defined. By utilizing a new technique, we define how HIV-1 interacts with different tissues of the FRT using human cervical explants and in vivo exposure in the rhesus macaque vaginal transmission model. Despite previous claims of the squamous epithelium being an efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact columnar and squamous epithelial barriers to depths where the virus can encounter potential target cells. In the squamous epithelium, we identify virus entry occurring through diffusive percolation, penetrating areas where cell junctions are absent. In the columnar epithelium, we illustrate that virus does not transverse barriers as well as previously thought due to mucus impediment. We also show a statistically significant correlation between the viral load of inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our results suggest a diffusive percolation mechanism for the initial events of HIV-1 entry. With these data, we also mathematically extrapolate the number of HIV-1 particles that penetrate the mucosa per coital act, providing a biological description of the mechanism for HIV-1 transmission during the acute and chronic stages of infection.
authors: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Ann M
authors: AM
authors: Carias
authors: Scott
authors: S
authors: McCoombe
authors: Michael
authors: M
authors: McRaven
authors: Meegan
authors: M
authors: Anderson
authors: Nicole
authors: N
authors: Galloway
authors: Nathan
authors: N
authors: Vandergrift
authors: Angela J
authors: AJ
authors: Fought
authors: John
authors: J
authors: Lurain
authors: Maurice
authors: M
authors: Duplantis
authors: Ronald S
authors: RS
authors: Veazey
authors: Thomas J
authors: TJ
authors: Hope
mesh_terms: D000818:Animals; D004848:Epithelium / Q000276:immunology / Q000821:virology; D005260:Female; D005836:Genitalia, Female / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D008253:Macaca mulatta; D008962:Models, Theoretical; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology*; D009924:Organ Culture Techniques; D060737:Reproductive Tract Infections / Q000276:immunology / Q000821:virology*; D019562:Viral Load
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