The vast majority of newly acquired HIV infections develop following exposure to HIV infectivity at mucosal surfaces. Oral exposure to semen from HIV seropositive donors can lead to primary HIV infection. Tonsil organ culture systems have been developed in order to investigate the cellular and molecular mechanisms that underlie HIV transmission in the oral cavity. By using semen from HIV-infected donors as a source of HIV infectivity, it is possible to construct an authentic model of HIV transmission across mucosal surfaces. The major goal of this proposal is to apply HIV infectivity in semen (HIV virions or HIV-infected cells) to intact tonsillar epithelial surfaces to track the dispersal of HIV infectivity immediately after exposure and then monitor the establishment of primary HIV infection. Novel procedures have been established for time-lapse confocal microscopy with live tissue that allow direct visualization of events occurring at, and immediately below the exposed epithelial surfaces. A comprehensive representation of HIV transmission can be derived by combining confocal microscopy with high resolution single-cell in situ hybridization and immunocytochemical detection methods, performed with transverse sections cut from the same tissues. Clear understanding of the cellular and molecular events that support HIV transmission at exposed mucosal surfaces, and recognition of changes induced by semen, will contribute significantly towards the development of protective strategies to reduce the overall frequency of HIV transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DE015090-01
Application #
6596475
Study Section
Special Emphasis Panel (ZDE1-YL (70))
Program Officer
Nokta, Mostafa A
Project Start
2002-09-01
Project End
2004-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
1
Fiscal Year
2002
Total Cost
$214,354
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Southern, Peter; Horbul, Julie; Maher, Diane et al. (2008) C. albicans colonization of human mucosal surfaces. PLoS One 3:e2067
Estes, Jacob D; Wietgrefe, Stephen; Schacker, Timothy et al. (2007) Simian immunodeficiency virus-induced lymphatic tissue fibrosis is mediated by transforming growth factor beta 1-positive regulatory T cells and begins in early infection. J Infect Dis 195:551-61
Kumar, Renu B; Maher, Diane M; Herzberg, Mark C et al. (2006) Expression of HIV receptors, alternate receptors and co-receptors on tonsillar epithelium: implications for HIV binding and primary oral infection. Virol J 3:25
Maher, Diane; Wu, Xiaoyun; Schacker, Timothy et al. (2005) HIV binding, penetration, and primary infection in human cervicovaginal tissue. Proc Natl Acad Sci U S A 102:11504-9
Maher, Diane M; Zhang, Zhi-Qiang; Schacker, Timothy W et al. (2005) Ex vivo modeling of oral HIV transmission in human palatine tonsil. J Histochem Cytochem 53:631-42
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