A Novel Approach for Preventing HIV Infection and Reducing Risk to U.S. Military Personnel
Annual rept. 10 Aug 2012-9 Aug 2013
GLADSTONE INSTITUTES SAN FRANCISCO CA
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The most common mode of HIV transmission is through sexual contact, and as such semen is the vector that is fueling the worldwide spread of the virus. We and our colleagues have identified and characterized amyloid fibrils from human semen that substantially promote HIV infection. In our funded proposal, we describe experiments to study the components of semen that enhance HIV infection, to decipher their mechanisms of action both in vitro and in vivo, and to identify methods of blocking their activity. We have made significant progress in our first year of the funded proposal. In addition to identifying a novel set of viral enhancing factors from semen, we have identified new mechanisms by which these amyloids can promote HIV transmission. We have shown an association between the levels of semen amyloids with endogenous viral load in samples form HIV-infected men, and demonstrated the activity of the amyloids in vivo in a humanized mouse model of HIV transmission. Finally, we have initiated a small-molecule screen for inhibitors of these amyloids, and have identified promising hits that we are currently further testing in secondary analysis. Inhibiting the activity of these semen factors can lead to the development of a new generation of microbicides targeting HIV together with naturally-occurring viral enhancement factors.
- Medicine and Medical Research
- Military Forces and Organizations