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

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• 作者：David Easterhoff^† ; ; ; John  ; T.M. DiMaio^‡ ; ; ; Todd  ; M. Doran^‡ ; ; Stephen Dewhurst^† ; ; ^{stephen_dewhurst@urmc.rochester.edu} ; Bradley  ; L. Nilsson^‡ ; ; ^{nilsson@chem.rochester.edu}
• 刊名：Biophysical Journal
• 出版年：2011
• 出版时间：2 March 2011
• 年：2011
• 卷：100
• 期：5
• 页码：1325-1334
• 全文大小：991 K

文摘

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.