title: Peptides released by physiological cleavage of semen coagulum proteins form amyloids that enhance HIV infection.
abstract: Semen serves as a vehicle for HIV and promotes sexual transmission of the virus, which accounts for the majority of new HIV cases. The major component of semen is the coagulum, a viscous structure composed predominantly of spermatozoa and semenogelin proteins. Due to the activity of the semen protease PSA, the coagulum is liquefied and semenogelins are cleaved into smaller fragments. Here, we report that a subset of these semenogelin fragments form amyloid fibrils that greatly enhance HIV infection. Like SEVI, another amyloid fibril previously identified in semen, the semenogelin fibrils exhibit a cationic surface and enhance HIV virion attachment and entry. Whereas semen samples from healthy individuals greatly enhance HIV infection, semenogelin-deficient semen samples from patients with ejaculatory duct obstruction are completely deficient in enhancing activity. Semen thus harbors distinct amyloidogenic peptides derived from different precursor proteins that commonly enhance HIV infection and likely contribute to HIV transmission.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94158, USA.
authors.forename: Nadia R
authors.initials: NR
authors.lastname: Roan
authors.forename: Janis A
authors.initials: JA
authors.lastname: Müller
authors.forename: Haichuan
authors.initials: H
authors.lastname: Liu
authors.forename: Simon
authors.initials: S
authors.lastname: Chu
authors.forename: Franziska
authors.initials: F
authors.lastname: Arnold
authors.forename: Christina M
authors.initials: CM
authors.lastname: Stürzel
authors.forename: Paul
authors.initials: P
authors.lastname: Walther
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
authors.forename: H Ewa
authors.initials: HE
authors.lastname: Witkowska
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.forename: Jan
authors.initials: J
authors.lastname: Münch
authors.forename: Warner C
authors.initials: WC
authors.lastname: Greene
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012661:Semen / Q000737:chemistry / Q000378:metabolism*; D029607:Seminal Vesicle Secretory Proteins / Q000737:chemistry / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D000682:Amyloid; D010455:Peptides; D029607:Seminal Vesicle Secretory Proteins; C424482:seminal vesicle-specific antigen