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

Paxton, W. A., Kang, S., Liu, R., Landau, N. R., Gingeras, T. R., Wu, L., Mackay, C. R., Koup, R. A. (1999) HIV-1 infectability of CD4+ lymphocytes with relation to β-chemokines and the CCR5 coreceptor. Immunology Letters, 66 (1-3). pp. 71-75. ISSN 01652478 (ISSN)

DOI: 10.1016/s0165-2478(98)00154-0


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.

Item Type: Paper
Uncontrolled Keywords: CCR5 Chemokine coreceptors HIV-1 resistance Macrophage tropism beta chemokine chemokine receptor ccr5 conference paper helper cell human human cell human immunodeficiency virus 1 human immunodeficiency virus infection infection resistance priority journal virus cell interaction virus replication virus transmission CD4-Positive T-Lymphocytes Chemokines CC Genotype HIV-1 Humans Phenotype Receptors CCR5
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
organism description > virus
CSHL Authors:
Communities: CSHL labs > Gingeras lab
Depositing User: CSHL Librarian
Date: 1999
Date Deposited: 13 Mar 2012 16:35
Last Modified: 27 Mar 2014 20:31
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