Epigallocatechin Gallate Inhibits Macaque SEVI-Mediated Enhancement of SIV or SHIV Infection.
Human semen contains a factor that can enhance HIV infection up to 10-fold in cultures. This factor is termed semen-derived enhancer of virus infection (SEVI) and is composed of proteolytic fragments (PAP248-286) from prostatic acid phosphatase in semen. In this study, we examined whether macaque SEVI can facilitate simian immunodeficiency virus (SIV) or chimeric simian/human immunodeficiency virus (SHIV) infection. We also studied the effect of epigallocatechin gallate (EGCG) on macaque SEVI-mediated SIV or SHIV enhancement.



SIV or SHIV was mixed with different concentrations of macaque SEVI in the presence or absence of EGCG. The mixture was added to cultures of TZM-bl cells or macaque PBMCs. The effect of EGCG on macaque SEVI was measured by Congo-red staining assay and thioflavin T (ThT) fluorescence assay and was visualized by a transmission electron microscope.



We identified that there is one amino acid difference at the site of 277 between human PAP248-286 and macaque PAP248-286. Macaque SEVI significantly enhanced SIV or SHIV infection of TZM-bl cells and macaque PBMCs. EGCG could block macaque SEVI-mediated enhancement of SIV or SHIV infection. Mechanistically, EGCG could degrade the formation of macaque SEVI amyloid fibrils that facilitates HIV attachment to the target cells.



The finding that macaque SEVI could enhance SIV or SHIV infection indicates the possibility to use the macaque SEVI in vivo studies with the macaque models. In addition, future studies are necessary to examine whether EGCG can be used as an effective microbicide for preventing SIV or SHIV mucosal transmission.
*School of Basic Medical Sciences/State Key Laboratory of Virology, Wuhan University, Wuhan, China; †Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA; and ‡School of Public Health, Guangxi Medical University, Nanning, China.
Run-Hong
RH
Zhou
Le
L
Guo
Jin-Biao
JB
Liu
Hang
H
Liu
Wei
W
Hou
Tong-Cui
TC
Ma
Xu
X
Wang
Jian-Guo
JG
Wu
Li
L
Ye
Wen-Zhe
WZ
Ho
Jie-Liang
JL
Li
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008251:Macaca; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000821:virology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011485:Protein Binding; D012661:Semen / Q000187:drug effects / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000472:pathogenicity*; D053585:Virus Attachment / Q000187:drug effects
D011480:Protease Inhibitors; D002392:Catechin; C045651:epigallocatechin gallate