ADS-J1 Inhibits Semen-Derived Amyloid Fibril Formation and Blocks Fibril-Mediated Enhancement of HIV-1 Infection | Zendy

Tianrong Xun | Zendy; Wenjuan Li | Zendy; Chen Jin-quan | Zendy; Fei Yu | Zendy; Wei Xu | Zendy; Qian Wang | Zendy; Ruizhe Yu | Zendy; Xiaojuan Li | Zendy; Xuefeng Zhou | Zendy; Lu Lu | Zendy; Shibo Jiang | Zendy; Lin Li | Zendy; Suiyi Tan | Zendy; Shuwen Liu | Zendy

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ADS-J1 Inhibits Semen-Derived Amyloid Fibril Formation and Blocks Fibril-Mediated Enhancement of HIV-1 Infection

Author(s) -

Tianrong Xun,

Wenjuan Li,

Chen Jin-quan,

Fei Yu,

Wei Xu,

Qian Wang,

Ruizhe Yu,

Xiaojuan Li,

Xuefeng Zhou,

Lu Lu,

Shibo Jiang,

Lin Li,

Suiyi Tan,

Shuwen Liu

Publication year - 2015

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.00385-15

Subject(s) - microbicide , fibril , sexual transmission , internalization , peptide , infectivity , semen , cytotoxicity , chemistry , viral entry , amyloid (mycology) , in vitro , microbiology and biotechnology , virology , biophysics , biology , biochemistry , virus , human immunodeficiency virus (hiv) , viral replication , cell , anatomy , inorganic chemistry

Semen-derived enhancer of viral infection (SEVI) is composed of amyloid fibrils that can greatly enhance HIV-1 infectivity. By its cationic property, SEVI promotes viral sexual transmission by facilitating the attachment and internalization of HIV-1 to target cells. Therefore, semen-derived amyloid fibrils are potential targets for microbicide design. ADS-J1 is an anionic HIV-1 entry inhibitor. In this study, we explored an additional function of ADS-J1: inhibition of SEVI fibril formation and blockage of SEVI-mediated enhancement of viral infection. We found that ADS-J1 bound to an amyloidogenic peptide fragment (PAP248–286 , comprising amino acids 248 to 286 of the enzyme prostatic acid phosphatase), thereby inhibiting peptide assembly into amyloid fibrils. In addition, ADS-J1 binds to mature amyloid fibrils and antagonizes fibril-mediated enhancement of viral infection. Unlike cellulose sulfate, a polyanion that failed in clinical trial to prevent HIV-1 sexual transmission, ADS-J1 shows no ability to facilitate fibril formation. More importantly, the combination of ADS-J1 with several antiretroviral drugs exhibited synergistic effects against HIV-1 infection in semen, with little cytotoxicity to vaginal epithelial cells. Our results suggest that ADS-J1 or a derivative may be incorporated into a combination microbicide for prevention of the sexual transmission of HIV-1.

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