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Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract

Carias, Ann M., McCoombe, Scott, McRaven, Michael, Anderson, Meegan, Galloway, Nicole, Vandergrift, Nathan, Fought, Angela J., Lurain, John, Duplantis, Maurice, Veazey, Ronald S. and Hope, Thomas J. 2013, Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract, Journal of virology, vol. 87, no. 21, pp. 11388-11400, doi: 10.1128/JVI.01377-13.

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Title Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract
Author(s) Carias, Ann M.
McCoombe, ScottORCID iD for McCoombe, Scott orcid.org/0000-0001-6717-7511
McRaven, Michael
Anderson, Meegan
Galloway, Nicole
Vandergrift, Nathan
Fought, Angela J.
Lurain, John
Duplantis, Maurice
Veazey, Ronald S.
Hope, Thomas J.
Journal name Journal of virology
Volume number 87
Issue number 21
Start page 11388
End page 11400
Total pages 13
Publisher American Society for Microbiology
Place of publication Washington, D.C.
Publication date 2013-11
ISSN 1098-5514
Summary 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.
Language eng
DOI 10.1128/JVI.01377-13
Field of Research 110799 Immunology not elsewhere classified
Socio Economic Objective 920109 Infectious Diseases
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Persistent URL http://hdl.handle.net/10536/DRO/DU:30073320

Document type: Journal Article
Collection: School of Medicine
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