Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection

Cell   Dec. 14, 2007  Vol.131 N.6  p.1059-1071 

Article

 

Jan Münch,1 Elke Rücker,1 Ludger Ständker,2,3 Knut Adermann,2,3,4 Christine Goffinet,5 Michael Schindler,1 Steffen Wildum,1 Raghavan Chinnadurai,1 Devi Rajan,1 Anke Specht,1 Guillermo Giménez-Gallego,6 Pedro Cuevas Sánchez,7 Douglas M. Fowler,8 Atanas Koulov,8 Jeffery W. Kelly,8 Walther Mothes,9 Jean-Charles Grivel,10 Leonid Margolis,10 Oliver T. Keppler,5 Wolf-Georg Forssmann,2,3, and Frank Kirchhoff1,

1 Institute of Virology, University Clinic of Ulm, 89081 Ulm, Germany
2 IPF PharmaCeuticals GmbH, 30625 Hannover, Germany
3 Hannover Medical School, Center of Pharmacology, 30625 Hannover, Germany
4 VIRO Pharmaceuticals GmbH & Co. KG, 30625 Hannover, Germany
5 Department of Virology, University of Heidelberg, 69120 Heidelberg, Germany
6 Centro de Investigaciones Biológicas (CIB/CSIC), Madrid 28040, Spain
7 Hospital Ramón y Cajal, Madrid 28034, Spain
8 Department of Chemistry and the Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
9 Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA
10 National Institute of Child Health and Human Development, Bethesda, MD 20892, USA

 

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.

 

abstract
http://www.cell.com/content/article/abstract?uid=PIIS0092867407012846