Adaptation of the human immunodeficiency virus type 1 envelope glycoproteins to new world monkey receptors

J Virol. 2008 Jan;82(1):346-57. doi: 10.1128/JVI.01299-07. Epub 2007 Oct 24.

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection encounters an early block in the cells of New World monkeys because the CD4 receptor does not efficiently support HIV-1 entry. We adapted HIV-1(NL4-3) and HIV-1(KB9), two HIV-1 variants with different envelope glycoproteins, to replicate efficiently in cells expressing the CD4 and CXCR4 proteins of the common marmoset, a New World monkey. The HIV-1(NL4-3) adaptation involves three gp120 changes that result in a specific increase in affinity for the marmoset CD4 glycoprotein. The already high affinity of the HIV-1(KB9) envelope glycoproteins for marmoset CD4 did not significantly change as a result of the adaptation. Instead, changes in the gp120 variable loops and gp41 ectodomain resulted in improved replication in cells expressing the marmoset receptors. HIV-1(KB9) became relatively sensitive to neutralization by soluble CD4 and antibodies as a result of the adaptation. These results demonstrate the distinct mechanistic pathways by which the HIV-1 envelope glycoproteins can adapt to less-than-optimal CD4 molecules and provide HIV-1 variants that can overcome some of the early blocks in New World monkey cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological*
  • Animals
  • CD4 Antigens / metabolism
  • Callithrix
  • Cell Line
  • 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 / growth & development*
  • Humans
  • Platyrrhini / virology*
  • Receptors, Virus / metabolism

Substances

  • CD4 Antigens
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Receptors, Virus
  • gp120 protein, Human immunodeficiency virus 1
  • gp41 protein, Human immunodeficiency virus 1