Reduced HIV-1 infectability of CD4+ lymphocytes from exposed-uninfected individuals: association with low expression of CCR5 and high production of beta-chemokines

Virology. 1998 Apr 25;244(1):66-73. doi: 10.1006/viro.1998.9082.


We examined the human immunodeficiency virus type 1 infectability of CD4+ lymphocytes isolated from CCR5 wild-type individuals, individuals heterozygous for the delta32 allele of CCR5, and HIV-1-exposed but uninfected (EU) individuals who had CD4+ lymphocytes refractory to M-tropic viral replication. None of the EU individuals were found to be heterozygous for the delta32 allele. The CD4+ lymphocytes isolated from CCR5/delta32 and EU individuals were less infectable with an M-tropic viral isolate of HIV-1 than CCR5/CCR5 control individuals but were equally as infectable with a T-tropic viral isolate. The restriction to M-tropic viral isolate replication did not associate with any profound genotypic change in the CCR5 gene. CD4+ lymphocytes from CCR5/delta32 and CCR5/CCR5 EU individuals were more sensitive to the HIV-inhibitory effects of the recombinant beta-chemokines RANTES, MIP-1alpha, and MIP-1beta than were CD4+ lymphocytes from CCR5/CCR5 control individuals. CD4+ lymphocytes from EU individuals also showed increased sensitivity to recombinant beta-chemokines and low surface expression of CCR5. A phenotype of low CCR5 expression and high secretion of beta-chemokines is associated with reduced infectability of cells by M-tropic HIV-1. This phenotype may also be associated with protection against sexual transmission of HIV-1.

Publication types

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

MeSH terms

  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Line, Transformed
  • Cell Membrane / metabolism
  • Chemokine CCL5 / metabolism
  • Chemokines / immunology
  • Chemokines / metabolism*
  • Genotype
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Humans
  • Receptors, CCR5 / biosynthesis*
  • Receptors, CCR5 / genetics
  • Recombinant Proteins / pharmacology


  • Chemokine CCL5
  • Chemokines
  • Receptors, CCR5
  • Recombinant Proteins