Semen-derived amyloid fibrils drastically enhance HIV infection

被引：443

作者：

Muench, Jan ^{[2
]}

Ruecker, Elke ^{[2
]}

Staendker, Ludger ^{[1
,3
]}

Adermann, Knut ^{[1
,3
,4
]}

Goffinet, Christine ^{[5
]}

Schindler, Michael ^{[2
]}

Wildum, Steffen ^{[2
]}

Chinnadurai, Raghavan ^{[2
]}

Rajan, Devi ^{[2
]}

Specht, Anke ^{[2
]}

Gimenez-Gallego, Guillermo ^{[6
]}

Cuevas Sanchez, Pedro ^{[7
]}

Fowler, Douglas M. ^{[8
,9
]}

Koulov, Atanas ^{[8
,9
]}

Kelly, Jeffery W. ^{[8
,9
]}

Mothes, Walther ^{[10
]}

Grivel, Jean-Charles ^{[11
]}

Margolis, Leonid ^{[11
]}

Keppler, Oliver T. ^{[5
]}

Forssmann, Wolf-Georg ^{[1
,3
]}

Kirchhoff, Frank ^{[2
]}

机构：

[1] IPF PharmaCeut GmbH, D-30625 Hannover, Germany

[2] Univ Clin Ulm, Inst Virol, D-89081 Ulm, Germany

[3] Hannover Med Sch, Ctr Pharmacol, D-30625 Hannover, Germany

[4] VIRO Pharmaceut GmbH & Co KG, D-30625 Hannover, Germany

[5] Heidelberg Univ, Dept Virol, D-69120 Heidelberg, Germany

[6] CSIC, Ctr Invest Biol, Madrid 28040, Spain

[7] Hosp Ramon & Cajal, E-28034 Madrid, Spain

[8] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[9] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[10] Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA

[11] NICHHD, Bethesda, MD 20892 USA

来源：

CELL | 2007年 / 131卷 / 06期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.cell.2007.10.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1059 / 1071

页数：13

共 44 条

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