HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth.

Published

Journal Article (Review)

The HIV-1 gp120 envelope (Env) glycoprotein mediates attachment of virus to human target cells that display requisite receptors, CD4 and co-receptor, generally CCR5. Despite high-affinity interactions with host receptors and proof-of-principle by the drug maraviroc that interference with CCR5 provides therapeutic benefit, no licensed drug currently targets gp120.An overview of the role of gp120 in HIV-1 entry and of sites of potential gp120 vulnerability to therapeutic inhibition is presented. Viral defenses that protect these sites and turn gp120 into a moving labyrinth are discussed together with strategies for circumventing these defenses to allow therapeutic targeting of gp120 sites of vulnerability.The gp120 envelope glycoprotein interacts with host proteins through multiple interfaces and has conserved structural features at these interaction sites. In spite of this, targeting gp120 for therapeutic purposes is challenging. Env mechanisms that have evolved to evade the humoral immune response also shield it from potential therapeutics. Nevertheless, substantial progress has been made in understanding HIV-1 gp120 structure and its interactions with host receptors, and in developing therapeutic leads that potently neutralize diverse HIV-1 strains. Synergies between advances in understanding, needs for therapeutics against novel viral targets and characteristics of breadth and potency for a number of gp120-targetting lead molecules bodes well for gp120 as a HIV-1 therapeutic target.

Full Text

Duke Authors

Cited Authors

  • Acharya, P; Lusvarghi, S; Bewley, CA; Kwong, PD

Published Date

  • June 2015

Published In

Volume / Issue

  • 19 / 6

Start / End Page

  • 765 - 783

PubMed ID

  • 25724219

Pubmed Central ID

  • 25724219

Electronic International Standard Serial Number (EISSN)

  • 1744-7631

International Standard Serial Number (ISSN)

  • 1472-8222

Digital Object Identifier (DOI)

  • 10.1517/14728222.2015.1010513

Language

  • eng