Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Oct 6;292(40):16511-16512.
doi: 10.1074/jbc.H117.791731.

How entry inhibitors synergize to fight HIV

Gregory B Melikyan  1
Affiliations
Review

How entry inhibitors synergize to fight HIV

Gregory B Melikyan. J Biol Chem. .

Abstract

HIV fusion with the cell membrane can be inhibited by blocking coreceptor binding or by preventing fusion-inducing conformational changes in the Env protein. Logically, inhibitors that act by these two mechanisms should act synergistically, but previous studies have reported conflicting results. A new study by Ahn and Root reconciles these discordant reports by demonstrating that synergy emerges when Env engages multiple coreceptors prior to inducing fusion and when high-affinity inhibitory peptides are used, a condition that may not be satisfied in vivo.

PubMed Disclaimer

Conflict of interest statement

The author declares that he has no conflicts of interest with the contents of this article. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.

Figures

Figure 1.
Figure 1.
A model for HIV Env-mediated fusion. Fusion-promoting conformational changes in Env glycoprotein mediated by binding to CD4 and coreceptor are illustrated. Red and blue rectangles represent N- and C-terminal heptad repeat domains of gp41, respectively; orange boxes are the fusion peptides.
See this image and copyright information in PMC

References

    1. Berger E. A., Doms R. W., Fenyö E. M., Korber B. T., Littman D. R., Moore J. P., Sattentau Q. J., Schuitemaker H., Sodroski J., and Weiss R. A. (1998) A new classification for HIV-1. Nature 391, 240. - PubMed
    1. Wilen C. B., Tilton J. C., and Doms R. W. (2012) Molecular mechanisms of HIV entry. Adv. Exp. Med. Biol. 726, 223–242 - PubMed
    1. Melikyan G. B. (2008) Common principles and intermediates of viral protein-mediated fusion: The HIV-1 paradigm. Retrovirology 5, 111. - PMC - PubMed
    1. Champagne K., Shishido A., and Root M. J. (2009) Interactions of HIV-1 inhibitory peptide T20 with the gp41 N-HR coiled coil. J. Biol. Chem. 284, 3619–3627 - PMC - PubMed
    1. Kahle K. M., Steger H. K., and Root M. J. (2009) Asymmetric deactivation of HIV-1 gp41 following fusion inhibitor binding. PLoS Pathog. 5, e1000674. - PMC - PubMed

MeSH terms