Semen Factor Increases Infectivity of HIV

[sharon sanders]

Article

Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection

Jan M?nch¹, Elke R?cker¹, Ludger St?ndker²^,³, Knut Adermann²^,³^,⁴, Christine Goffinet⁵, Michael Schindler¹, Steffen Wildum¹, Raghavan Chinnadurai¹, Devi Rajan¹, Anke Specht¹, Guillermo Gim?nez-Gallego⁶, Pedro Cuevas S?nchez⁷, Douglas M. Fowler⁸, Atanas Koulov⁸, Jeffery W. Kelly⁸, Walther Mothes⁹, Jean-Charles Grivel¹⁰, Leonid Margolis¹⁰, Oliver T. Keppler⁵, Wolf-Georg Forssmann²^,³^,^, and Frank Kirchhoff¹^,^,
¹Institute of Virology, University Clinic of Ulm, 89081 Ulm, Germany
²IPF PharmaCeuticals GmbH, 30625 Hannover, Germany
³Hannover Medical School, Center of Pharmacology, 30625 Hannover, Germany
⁴VIRO Pharmaceuticals GmbH & Co. KG, 30625 Hannover, Germany
⁵Department of Virology, University of Heidelberg, 69120 Heidelberg, Germany
⁶Centro de Investigaciones Biol?gicas (CIB/CSIC), Madrid 28040, Spain
⁷Hospital Ram?n y Cajal, Madrid 28034, Spain
⁸Department of Chemistry and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
⁹Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA
¹⁰National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
Received 6 February 2007; revised 18 June 2007; accepted 4 October 2007. Published: December 13, 2007. Available online 13 December 2007.

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</td><td>A Seminal Finding for Understanding HIV Transmission
Cell, Volume 131, Issue 6, 14 December 2007, Pages 1044-1046
Nadia R. Roan and Warner C. Greene
Abstract | Full Text + Links | PDF (334 K) </td></tr><tr class="refersDivider"><td colspan="3">
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Summary

Sexual intercourse is the major route of HIV transmission. To identify endogenous factors that affect the efficiency of sexual viral transmission, we screened a complex peptide/protein library derived from human semen. We show that naturally occurring fragments of the abundant semen marker prostatic acidic phosphatase (PAP) form amyloid fibrils. These fibrils, termed Semen-derived Enhancer of Virus Infection (SEVI), capture HIV virions and promote their attachment to target cells, thereby enhancing the infectious virus titer by several orders of magnitude. Physiological concentrations of SEVI amplified HIV infection of T cells, macrophages, ex vivo human tonsillar tissues, and transgenic rats in vivo, as well as trans-HIV infection of T cells by dendritic or epithelial cells. Amyloidogenic PAP fragments are abundant in seminal fluid and boost semen-mediated enhancement of HIV infection. Thus, they may play an important role in sexual transmission of HIV and could represent new targets for its prevention.