Aminoquinoline surfen inhibits the action of SEVI (semen-derived enhancer of viral infection).
In semen, proteolytic peptide fragments from prostatic acid phosphatase can form amyloid fibrils termed SEVI (semen-derived enhancer of viral infection). These fibrils greatly enhance human immunodeficiency virus (HIV) infectivity by increasing the attachment of virions to target cells. Therefore, SEVI may have a significant impact on whether HIV is successfully transmitted during sexual contact. Here, we demonstrate that surfen, a small molecule heparan sulfate proteoglycan antagonist, inhibits both SEVI- and semen-mediated enhancement of HIV type 1 infection. Surfen interferes with the binding of SEVI to both target cells and HIV type 1 virions but does not deaggregate SEVI fibrils. Because SEVI can increase HIV infectivity by several orders of magnitude, supplementing current HIV microbicide candidates with SEVI inhibitors, such as surfen, might greatly increase their potency.
Roan
Nadia R
NR
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94158, USA.
Sowinski
Stefanie
S
Münch
Jan
J
Kirchhoff
Frank
F
Greene
Warner C
WC
D000634:Aminoquinolines / Q000494:pharmacology* / Q000627:therapeutic use; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019812:Heparan Sulfate Proteoglycans / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D051379:Mice; D051381:Rats; D012661:Semen / Q000187:drug effects* / Q000378:metabolism* / Q000821:virology; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014771:Virion / Q000187:drug effects / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects
D000634:Aminoquinolines; D000682:Amyloid; D019380:Anti-HIV Agents; D019812:Heparan Sulfate Proteoglycans; C010850:aminoquinuride; D014508:Urea