HIV binding, penetration, and primary infection in human cervicovaginal tissue
- Departments of *Microbiology and ‡Medicine, University of Minnesota Medical School, MMC 196, 420 Delaware Street Southeast, Minneapolis, MN 55455; and †Department of Medicine, University of Alabama at Birmingham, 1530 Third Avenue South, Birmingham, AL 35294
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Edited by Robert C. Gallo, University of Maryland Biotechnology Institute, Baltimore, MD (received for review February 1, 2005)
Abstract
We have developed human cervicovaginal organ culture systems to examine the initiating events in HIV transmission after exposure to various sources of HIV infectivity, including semen. Newly infected cells were detected in the cervical submucosa 3–4 days after exposure to a primary HIV isolate. At earlier times, extensive and stable binding occurred when cervical surfaces were exposed to virions or seminal cells. Cervical mucus provided some protection for the endocervical surface, by physically trapping virions and seminal cells. Confocal microscopy combined with 3D surface reconstruction revealed that virions could both bind to the external surface of the cervical epithelium and actually penetrate beneath the epithelial surface. In quantitative assays, pretreatment with a blocking antibody directed against β1 integrin reduced HIV virion binding. Collectively, these results highlight a continuum of complex interactions that occurs when natural sources of HIV infectivity are deposited onto mucosal surfaces in the female reproductive tract.
Footnotes
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↵ § To whom correspondence should be addressed. E-mail: peter{at}mail.ahc.umn.edu.
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Author contributions: D.M. and P.S. designed research; D.M., J.H., and P.S. performed research; D.M., X.W., and T.S. contributed new reagents/analytical tools; D.M., J.H., and P.S. analyzed data; and D.M. and P.S. wrote the paper.
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This paper was submitted directly (Track II) to the PNAS office.
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Abbreviation: SIV, simian immunodeficiency virus.
- Copyright © 2005, The National Academy of Sciences
