Semen-derived amyloid fibrils drastically enhance HIV infection.
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.
Münch
Jan
J
Institute of Virology, University Clinic of Ulm, 89081 Ulm, Germany.
Rücker
Elke
E
Ständker
Ludger
L
Adermann
Knut
K
Goffinet
Christine
C
Schindler
Michael
M
Wildum
Steffen
S
Chinnadurai
Raghavan
R
Rajan
Devi
D
Specht
Anke
A
Giménez-Gallego
Guillermo
G
Sánchez
Pedro Cuevas
PC
Fowler
Douglas M
DM
Koulov
Atanas
A
Kelly
Jeffery W
JW
Mothes
Walther
W
Grivel
Jean-Charles
JC
Margolis
Leonid
L
Keppler
Oliver T
OT
Forssmann
Wolf-Georg
WG
Kirchhoff
Frank
F
D000135:Acid Phosphatase; D000682:Amyloid / Q000302:isolation & purification / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D015658:HIV Infections / Q000635:transmission*; D006801:Humans; D010446:Peptide Fragments / Q000502:physiology*; D019151:Peptide Library; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000502:physiology*; D051381:Rats; D012661:Semen / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D015229:Sexually Transmitted Diseases, Viral / Q000378:metabolism*; D019562:Viral Load
D000682:Amyloid; D010446:Peptide Fragments; D019151:Peptide Library; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; C526435:prostatic acid phosphatase (248-286), human; D017027:Protein Tyrosine Phosphatases