Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection

Jan Münch, Elke Rücker, Ludger Ständker, Knut Adermann, Christine Goffinet, Michael Schindler, Steffen Wildum, Raghavan Chinnadurai, Devi Rajan, Anke Specht, Guillermo Giménez-Gallego, Pedro Cuevas Sánchez, Douglas M. Fowler, Atanas Koulov, Jeffery W. Kelly, Walther Mothes, Jean Charles Grivel, Leonid Margolis, Oliver T. Keppler, Wolf Georg ForssmannFrank Kirchhoff

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1059-1071
Number of pages13
JournalCell
Volume131
Issue number6
DOIs
Publication statusPublished - 14 Dec 2007

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Keywords

  • HUMDISEASE
  • PROTEINS

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Münch, J., Rücker, E., Ständker, L., Adermann, K., Goffinet, C., Schindler, M., Wildum, S., Chinnadurai, R., Rajan, D., Specht, A., Giménez-Gallego, G., Sánchez, P. C., Fowler, D. M., Koulov, A., Kelly, J. W., Mothes, W., Grivel, J. C., Margolis, L., Keppler, O. T., ... Kirchhoff, F. (2007). Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection. Cell, 131(6), 1059-1071. https://doi.org/10.1016/j.cell.2007.10.014