N-linked glycosylation of CXCR4 masks coreceptor function for CCR5-dependent human immunodeficiency virus type 1 isolates

J Virol. 2000 May;74(9):4404-13. doi: 10.1128/jvi.74.9.4404-4413.2000.


The chemokine receptors CXCR4 and CCR5 are the principal coreceptors for infection of X4 and R5 human immunodeficiency virus type 1 (HIV-1) isolates, respectively. Here we report on the unexpected observation that the removal of the N-linked glycosylation sites in CXCR4 potentially allows the protein to serve as a universal coreceptor for both X4 and R5 laboratory-adapted and primary HIV-1 strains. We hypothesize that this alteration unmasks existing common extracellular structures reflecting a conserved three-dimensional similarity of important elements of CXCR4 and CCR5 that are involved in HIV envelope glycoprotein (Env) interaction. These results may have far-reaching implications for the differential recognition of cell type-dependent glycosylated CXCR4 by HIV-1 isolates and their evolution in vivo. They also suggest a possible explanation for the various observations of restricted virus entry in some cell types and further our understanding of the framework of elements that represent the Env-coreceptor contact sites.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • Glycosylation
  • HIV-1 / isolation & purification
  • HIV-1 / metabolism*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Receptors, CCR5 / metabolism*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • Tumor Cells, Cultured


  • Receptors, CCR5
  • Receptors, CXCR4