Enhancement of HIV-1 Infectivity by Simple, Self-Assembling Modular Peptides

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 enhance...

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Bibliographic Details
Published in:Biophysical journal 2011-03, Vol.100 (5), p.1325-1334
Main Authors: Easterhoff, David, DiMaio, John T.M., Doran, Todd M., Dewhurst, Stephen, Nilsson, Bradley L.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
amyloid
anti-infective agents
Biophysics
Body fluids
Cell Line
Experiments
HIV
HIV infections
HIV-1 - drug effects
HIV-1 - pathogenicity
Human immunodeficiency virus
Human immunodeficiency virus 1
Models, Molecular
Molecular Sequence Data
pathogenicity
Peptides
Peptides - chemistry
Peptides - metabolism
Peptides - pharmacology
Protein
Protein Structure, Secondary
Solubility
Viral infections
viruses
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Summary: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.
ISSN:0006-3495
1542-0086
DOI:10.1016/j.bpj.2011.01.037