TY - JOUR
T1 - Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection
AU - Münch, Jan
AU - Rücker, Elke
AU - Ständker, Ludger
AU - Adermann, Knut
AU - Goffinet, Christine
AU - Schindler, Michael
AU - Wildum, Steffen
AU - Chinnadurai, Raghavan
AU - Rajan, Devi
AU - Specht, Anke
AU - Giménez-Gallego, Guillermo
AU - Sánchez, Pedro Cuevas
AU - Fowler, Douglas M.
AU - Koulov, Atanas
AU - Kelly, Jeffery W.
AU - Mothes, Walther
AU - Grivel, Jean Charles
AU - Margolis, Leonid
AU - Keppler, Oliver T.
AU - Forssmann, Wolf Georg
AU - Kirchhoff, Frank
PY - 2007/12/14
Y1 - 2007/12/14
N2 - 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.
AB - 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.
KW - HUMDISEASE
KW - PROTEINS
U2 - 10.1016/j.cell.2007.10.014
DO - 10.1016/j.cell.2007.10.014
M3 - Article
SN - 0092-8674
VL - 131
SP - 1059
EP - 1071
JO - Cell
JF - Cell
IS - 6
ER -