Principal Investigator

Stephen Dewhurst, Ph.D. University of Rochester work Box 672 601 Elmwood Ave Rochester NY 14642 office: MRBX 2-1110 p (585) 275-3216

Seminal Amyloid Fibrils: Innate Immune Mediators That Are Hijacked by HIV

The Semen-derived Enhancer of Viral Infection (SEVI) is a cationic amyloid fibril found in human semen, originally identified because of its ability to greatly enhance HIV-1 infection of target cells. SEVI is thought to mitigate the electrostatic repulsion between HIV and its target cells, thereby allowing HIV to more easily interact with target receptors on host cells. SEVI’s function as an enhancer of viral infection makes it an intriguing target for novel microbicides, aimed at reducing the spread of HIV.

At the same time, it seems overwhelmingly likely that SEVI’s normal biological function is unrelated to HIV. Consistent with this, we have shown that SEVI can bind a wide range of bacteria and that it enhances bacterial phagocytosis by macrophages. SEVI also accelerates clearance of Neisseria gonorrhoeae in a vaginal infection model. Current studies are testing whether other cationic amyloid fibrils that have recently been identified in semen also possess antimicrobial activity. In addition, we are conducting other experiments to test whether these unusual cationic fibrils may have additional biological functions.

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