Genetic and functional analysis of R5X4 human immunodeficiency virus type 1 envelope glycoproteins derived from two individuals homozygous for the CCR5delta32 allele

J Virol. 2006 Apr;80(7):3684-91. doi: 10.1128/JVI.80.7.3684-3691.2006.

Abstract

We characterized human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) isolated from two HIV-1-infected CCR5delta32 homozygotes. Envs from both subjects used CCR5 and CXCR4 for entry into transfected cells. Most R5X4 Envs were lymphocyte-tropic and used CXCR4 exclusively for entry into peripheral blood mononuclear cells (PBMC), but a subset was dually lymphocyte- and macrophage-tropic and used either CCR5 or CXCR4 for entry into PBMC and monocyte-derived macrophages. The persistence of CCR5-using HIV-1 in two CCR5delta32 homozygotes suggests the conserved CCR5 binding domain of Env is highly stable and provides new mechanistic insights important for HIV-1 transmission and persistence.

Publication types

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

MeSH terms

  • Alleles*
  • Amino Acid Sequence
  • Base Sequence
  • Cell Line
  • Cells, Cultured
  • Clone Cells
  • Gene Products, env / chemistry
  • Gene Products, env / genetics
  • Gene Products, env / metabolism*
  • Genes, Reporter
  • HIV-1 / physiology*
  • Homozygote
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / virology
  • Luciferases / metabolism
  • Male
  • Molecular Sequence Data
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / metabolism*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Sequence Homology, Amino Acid

Substances

  • Gene Products, env
  • Receptors, CCR5
  • Receptors, CXCR4
  • Luciferases

Associated data

  • GENBANK/DQ356577
  • GENBANK/DQ356584