title: Enhancement of HIV-1 infectivity by simple, self-assembling modular peptides.
abstract: Semen-derived enhancer of viral infection (SEVI), an amyloid fibril formed from a cationic peptide fragment of prostatic acidic phosphatase (PAP), dramatically enhances the infectivity of human immunodeficiency virus type 1 (HIV-1). Insoluble, sedimentable fibrils contribute to SEVI-mediated enhancement of virus infection. However, the SEVI-forming PAP(248-286) peptide is able to produce infection-enhancing structures much more quickly than it forms amyloid fibrils. This suggests that soluble supramolecular assemblies may enhance HIV-1 infection. To address this question, non-SEVI amyloid-like fibrils were derived from general amphipathic peptides of sequence Ac-K(n)(XKXE)(2)-NH(2). These cationic peptides efficiently self-assembled to form soluble, fibril-like structures that were, in some cases, able to enhance HIV-1 infection even more efficiently than SEVI. Experiments were also performed to determine whether agents that efficiently shield the charged surface of SEVI fibrils block SEVI-mediated infection-enhancement. To do this, we generated self-assembling anionic peptides of sequence Ac-E(n)(XKXE)(2)-NH(2). One of these peptides completely abrogated SEVI-mediated enhancement of HIV-1 infection, without altering HIV-1 infectivity in the absence of SEVI. Collectively, these data suggest that soluble SEVI assemblies may mediate infection-enhancement, and that anionic peptide supramolecular assemblies have the potential to act as anti-SEVI microbicides.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester, Rochester, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Easterhoff
authors.forename: John T M
authors.initials: JT
authors.lastname: DiMaio
authors.forename: Todd M
authors.initials: TM
authors.lastname: Doran
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Nilsson
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D012995:Solubility
chemical_list: D010455:Peptides