Sexual contact is a major mode of HIV-1 transmission, with an increasing number of transmissions occurring via heterosexual contact from males to females. Consequently, about 16 million women worldwide are infected with HIV-1. Heterosexual transmission includes both anal and vaginal sex; the estimated risk of infection from vaginal sex with an HIV-1 positive male ranges from 0.08% to 0.30% per sexual act (not including commercial sex workers). This is in contrast with the pooled risk estimate for anal intercourse, which at 1.7% is at least 5?6 times higher than the risk estimate for vaginal sex. These statistics indicate that HIV-1 transmission during vaginal sex faces unique vaginal defenses that prevent the transmission and/or early steps of HIV-1 infection. We have identified vaginal fluid exosomes (VFE) and shown that VFE can significantly reduce HIV-1 transmission in vitro. We hypothesize that VFE can constitute a barrier to HIV-1 transmission during heterosexual contact. To test this hypothesis, we will pursue the following Specific Aims: (1) Analyze VFE and determine their composition and their source; (3) Identify the step(s) of the HIV-1 life cycle that are targeted by VFE; and (3) Determine how VFE block HIV-1 transmission. Specific points of innovation include (1) identification of female-produced defenses against HIV-1 infection, (2) characterization of the newly discovered VFE, and (3) identification of the mechanism by which VFE inhibit HIV-1 transmission. Our research environment enables close collaboration between clinical and basic researchers, which is crucial for the successful outcome of this project.

Public Health Relevance

. Vaginal contact is a major mode of HIV-1 transmission. In this application, we propose to test the hypothesis that vaginal exosomes constitute one of the innate vaginal defenses, which limit the rate of HIV-1 transmission. The application relies on close collaboration between clinical and basic research scientists.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI127293-01A1
Application #
9348751
Study Section
AIDS Immunology and Pathogenesis Study Section (AIP)
Program Officer
Kuo, Lillian S
Project Start
2017-08-08
Project End
2019-07-31
Budget Start
2017-08-08
Budget End
2018-07-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Miscellaneous
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107