Mechanism and Structural Basis of SEVI-Mediated Enhancement of HIV Infection

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We have recently shown that semen - the major vehicle for the transmission of HIV/AIDS - contains amyloid peptide aggregates that drastically enhance HIV-1 infection. These amyloid structures are formed by naturally occurring fragments of the abundant semen marker prostatic acid phosphatase, and were termed ‘Semen-derived Enhancer of Virus Infection’ (SEVI). SEVI captures HIV-1 virions and promotes virion attachment to the cell, thereby increasing the infectious virus titer by several orders of magnitude. Our observations suggest that SEVI-mediated enhancement of HIV-1 infection may play a key role in the dissemination of HIV/AIDS in the human population. To determine the mechanisms of SEVI- and semenmediated enhancement of HIV infection and to explore how the virus enhancing effect of semen can be blocked, we here propose to combine our complementary expertise in HIV/AIDS and amyloids. Our results will provide novel insights into the mechanisms of sexual transmission of HIV/AIDS and may lead to new approaches to prevent it.