Envelope glycoprotein determinants of increased entry in a pathogenic simian-human immunodeficiency virus (SHIV-HXBc2P 3.2) passaged in monkeys

AIDS Res Hum Retroviruses. 2004 Feb;20(2):163-73. doi: 10.1089/088922204773004888.


Passage of a nonpathogenic simian-human immunodeficiency virus (SHIV-HXBc2) in monkeys resulted in changes in the viral envelope glycoproteins that are responsible for a dramatic increase in replication and pathogenicity in vivo. Here, we show that the envelope glycoproteins of the pathogenic SHIV-HXBc2P 3.2 mediate virus entry into rhesus monkey peripheral blood mononuclear cells (PBMC) more efficiently than the parental SHIV-HXBc2 envelope glycoproteins, and study the basis for this increase. Both parental and pathogenic SHIVs exclusively use CXCR4 as a coreceptor. The determinants of the increased entry associated with the SHIV-HXBc2P 3.2 envelope glycoproteins are located in both the gp120 and gp41 subunits. Changes in the gp120 V3 variable loop specify a decreased sensitivity to SDF-1, consistent with an increase in the affinity of the HXBc2P 3.2 gp120 glycoprotein for CXCR4. Thus, multiple changes in the gp120 variable loops and the gp41 ectodomain of a pathogenic SHIV cooperate to allow enhanced replicative capacity, which in part results from increased chemokine receptor binding.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / physiology
  • HIV Envelope Protein gp41 / genetics
  • HIV Envelope Protein gp41 / physiology
  • HIV-1 / genetics
  • HIV-1 / pathogenicity*
  • HIV-1 / physiology*
  • Humans
  • In Vitro Techniques
  • Leukocytes, Mononuclear / virology
  • Macaca mulatta
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology
  • Receptors, CXCR4 / physiology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / physiology
  • Recombination, Genetic
  • Retroviridae Proteins / genetics
  • Retroviridae Proteins / physiology
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / pathogenicity*
  • Simian Immunodeficiency Virus / physiology*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / physiology*
  • Virulence
  • Virus Replication


  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Membrane Glycoproteins
  • Receptors, CXCR4
  • Recombinant Fusion Proteins
  • Retroviridae Proteins
  • SIV envelope protein gp41
  • Viral Envelope Proteins
  • gp120 protein, Simian immunodeficiency virus