HIV-1 infectability of CD4+ lymphocytes with relation to β-chemokines and the CCR5 coreceptor

William A. Paxton, Stanley Kang, Rong Liu, Nathanial R. Landau, Thomas R. Gingeras, Lijun Wu, Charles R. Mackay, Richard A. Koup

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23 Citations (Scopus)

Abstract

CD4+ lymphocytes exhibit variable permissiveness to the replication of HIV-1. A cohort of sexually-exposed-yet-uninfected individuals were previously shown to have CD4+ lymphocytes refractory for M-tropic vital replication. In particular, two individuals from this population whose CD4+ lymphocytes exhibited complete resistance to M-tropic vital replication were later shown to be homozygous for a 32bp (Δ32) deletion in the gene encoding for CCR5. In screening diverse populations, HIV-1 infected individuals heterozygous for the Δ32 allele were statistically favored in their disease course to harbor lower vital loads and exhibit slower rates of CD4+ cell loss when compared to control CCR5 wild-type individuals. Further comparative analysis between individuals in the exposed but uninfected cohort who demonstrated intermediate levels of in vitro viral replication and CD4+ lymphocytes isolated from uninfected Δ32 heterozygous individuals indicate that reduced levels of in vitro M-tropic replication are a CCR5-related phenomenon: CD4+ lymphocytes from these individuals were more sensitive to the HIV-1 blocking effects of recombinant chemokines, displayed lower CCR5 cell surface expression levels and a proportionate increase in the production of RANTES when compared to CD4+ lymphocytes from control individuals. These results suggest that the CCR5 phenotype is important in determining the replicative capacity of M-tropic HIV-1 in vitro. The implications of these results with relation to HIV-1 transmission and disease progression are discussed.

Original languageEnglish
Pages (from-to)71-75
Number of pages5
JournalImmunology Letters
Volume66
Issue number1-3
DOIs
Publication statusPublished - 1 Mar 1999
Externally publishedYes

Keywords

  • CCR5
  • Chemokine coreceptors
  • HIV-1 resistance
  • Macrophage tropism

Cite this

Paxton, W. A., Kang, S., Liu, R., Landau, N. R., Gingeras, T. R., Wu, L., ... Koup, R. A. (1999). HIV-1 infectability of CD4+ lymphocytes with relation to β-chemokines and the CCR5 coreceptor. Immunology Letters, 66(1-3), 71-75. https://doi.org/10.1016/S0165-2478(98)00154-0