Hepatitis C virus NS5A anchor peptide disrupts human immunodeficiency virus

doi:10.1073/pnas.0801388105

Hepatitis C virus NS5A anchor peptide disrupts human immunodeficiency virus

Departments of *Immunology and
^†Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037;
^‡Department of Molecular Cell Biology and Immunology, VU University Medical Center, van de Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands; and
^§BIOQUAL, Inc., 9600 Medical Center Drive, Rockville, MD 20850

Contributed by Francis V. Chisari, February 12, 2008 (received for review December 7, 2007)

Abstract

In the absence of an effective vaccine, there is an urgent need for safe and effective antiviral agents to prevent transmission of HIV. Here, we report that an amphipathic α-helical peptide derived from the hepatitis C virus NS5A anchor domain (designated C5A in this article) that has been shown to be virocidal for the hepatitis C virus (HCV) also has potent antiviral activity against HIV. C5A exhibits a broad range of antiviral activity against HIV isolates, and it prevents infection of the three in vivo targets of HIV: CD4⁺ T lymphocytes, macrophages, and dendritic cells by disrupting the integrity of the viral membrane and capsid core while preserving the integrity of host membranes. C5A can interrupt an ongoing T cell infection, and it can prevent transmigration of HIV through primary genital epithelial cells, infection of mucosal target cells and transfer from dendritic cells to T cells ex vivo, justifying future experiments to determine whether C5A can prevent HIV transmission in vivo.

Footnotes

^¶To whom correspondence may be addressed. E-mail: fchisari{at}scripps.edu or gallay{at}scripps.edu
Author contributions: T.B.H.G., F.V.C., and P.A.G. designed research; M.D.B., G.C., L.d.W., S.S., U.C., and B.E.S.-B. performed research; T.B.H.G., F.V.C., and P.A.G. analyzed data; and F.V.C. and P.A.G. wrote the paper.
Conflict of interest statement: F.V.C. has a financial interest in Viriome, Inc., which has licensing rights to the information provided in this article.
This article contains supporting information online at www.pnas.org/cgi/content/full/0801388105/DCSupplemental.