Aminoquinoline surfen inhibits the action of SEVI (semen-derived enhancer of viral infection).

Abstract

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.

• Authors: Nadia R Roan, Stefanie Sowinski, Jan Münch, Frank Kirchhoff, Warner C Greene
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 3 Pg. 1861-9 (Jan 15 2010) ISSN: 1083-351X [Electronic] United States
• PMID: 19897482 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoquinolines
• Amyloid
• Anti-HIV Agents
• Heparan Sulfate Proteoglycans
• aminoquinuride
• Urea

Topics

• Aminoquinolines (pharmacology, therapeutic use)
• Amyloid (antagonists & inhibitors, metabolism)
• Animals
• Anti-HIV Agents (pharmacology, therapeutic use)
• Cell Line
• Dose-Response Relationship, Drug
• Gene Expression Regulation
• HIV Infections (drug therapy, metabolism)
• HIV-1 (drug effects, metabolism, physiology)
• Heparan Sulfate Proteoglycans (deficiency, metabolism)
• Humans
• Mice
• Rats
• Semen (drug effects, metabolism, virology)
• Urea (analogs & derivatives, pharmacology, therapeutic use)
• Virion (drug effects, metabolism)
• Virus Internalization (drug effects)