Variability OF HIV-1 V2 env domain for integrin binding: Clinical correlates

Virology. 2019 Sep:535:266-271. doi: 10.1016/j.virol.2019.07.019. Epub 2019 Jul 24.

Abstract

The HIV V2179-181 (HXB2 numbering) tripeptide mediates binding to α4β7 integrin, which is responsible for GALT homing. Our study aimed to assess V2 variability in naive HIV-1 infected patients and its association with clinical and viro-immunological features. Gp120 sequences were obtained from 322 subjects; length, potential N-linked glycosylation sites (PNGs), net-charge (NC) and 179-181tripeptide α4β7-binding-motif of V2 were evaluated. At multivariate analysis, lower V2 length and higher NC correlated with low CD4 cells; no association was found with PNGs. A greater variability pertained positions 162-163, 164-167, 169, 175-179, 187, 194 and 195 in B sequences, and 163 and 177 in X4 tropic viruses. LDV was the most common tripeptide. Asp180 was highly conserved; Leu179 was more frequently observed in non-B and in recent infections compared to others, while Val181 was found in recent infections and in MSM. Further studies to deeply explore the clinical significance of these associations are warranted.

Keywords: Gp-120; HIV-1; Integrins; V2 tripeptide; α4β7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Binding Sites
  • Glycosylation
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / metabolism*
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • HIV-1 / physiology*
  • Host Microbial Interactions*
  • Humans
  • Integrins / metabolism*
  • Polymorphism, Genetic
  • Protein Binding
  • Sequence Analysis, DNA

Substances

  • HIV Envelope Protein gp120
  • Integrins
  • gp120 protein, Human immunodeficiency virus 1