Enhancement of HIV-1 infectivity by simple, self-assembling modular peptides

David Easterhoff; John T.M. DiMaio; Todd M. Doran; Stephen Dewhurst; Bradley L. Nilsson

doi:10.1016/j.bpj.2011.01.037

Enhancement of HIV-1 infectivity by simple, self-assembling modular peptides

David Easterhoff, John T.M. DiMaio, Todd M. Doran, Stephen Dewhurst, Bradley L. Nilsson

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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-NH₂. 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-NH₂. 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.

Original language	English (US)
Pages (from-to)	1325-1334
Number of pages	10
Journal	Biophysical journal
Volume	100
Issue number	5
DOIs	https://doi.org/10.1016/j.bpj.2011.01.037
State	Published - Mar 2 2011
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by the following grants from the National Institutes of Health: No. R01AI084111 (to S.D., B.N., and D.E.) and No. T32AI049815 (to D.E.), as well as by a DuPont Young Professors Award (to B.N.) and a Creative and Novel Ideas in HIV Research (CNIHR) award (to B.N.). The mass spectroscopy facility in the Department of Chemistry was partially supported by a grant from the National Science Foundation (No. CHE-0840410).

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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-Kn(XKXE) 2-NH2. 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-NH2. 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.",

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Enhancement of HIV-1 infectivity by simple, self-assembling modular peptides

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