Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity

• DOI: 10.1186/s12977-018-0432-3
• Publication Date: 2018-07-16T07:57:26Z
• Authors: Ruxia Ren; Shuwen Yin; Baolong Lai; Lingzhen Ma; Jiayong Wen; Xuanxuan Zhang; Fangyuan Lai; Shuwen Liu; Lin Li
• Keywords: Male; Models, Molecular; 0301 basic medicine; Amyloid; Anti-HIV Agents; Molecular Conformation; Virus Attachment; HIV Infections; Cell Line; Protein Aggregates; 03 medical and health sciences; Semen; Humans; Amyloid fibrils; Flavonoids; Dose-Response Relationship, Drug; Research; Myricetin; Virion; HIV; Drug Synergism; Synergistic antiviral effects; RC581-607; 3. Good health; SEVI; Host-Pathogen Interactions; HIV-1; Immunologic diseases. Allergy; Protein Multimerization; Protein Binding

Semen is a critical vector for human immunodeficiency virus (HIV) sexual transmission and harbors seminal amyloid fibrils that can markedly enhance HIV infection. Semen-derived enhancer of viral infection (SEVI) is one of the best-characterized seminal amyloid fibrils. Due to their highly cationic properties, SEVI fibrils can capture HIV virions, increase viral attachment to target cells, and augment viral fusion. Some studies have reported that myricetin antagonizes amyloid β-protein (Aβ) formation; myricetin also displays strong anti-HIV activity in vitro.Here, we report that myricetin inhibits the formation of SEVI fibrils by binding to the amyloidogenic region of the SEVI precursor peptide (PAP248-286) and disrupting PAP248-286 oligomerization. In addition, myricetin was found to remodel preformed SEVI fibrils and to influence the activity of SEVI in promoting HIV-1 infection. Moreover, myricetin showed synergistic effects against HIV-1 infection in combination with other antiretroviral drugs in semen.Incorporation of myricetin into a combination bifunctional microbicide with both anti-SEVI and anti-HIV activities is a highly promising approach to preventing sexual transmission of HIV.