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

• Published in: Immunology letters 1999-03, Vol.66 (1), p.71-75
• Main Authors: Paxton, William A., Kang, Stanley, Liu, Rong, Landau, Nathanial R., Gingeras, Thomas R., Wu, Lijun, Mackay, Charles R., Koup, Richard A.
• Format: Article
• Language: English
• Subjects: AIDS/HIV; CCR5; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Chemokine coreceptors; Chemokines, CC - metabolism; Genotype; HIV-1 - metabolism; HIV-1 - physiology; HIV-1 resistance; Humans; Macrophage tropism; Phenotype; Receptors, CCR5 - genetics; Receptors, CCR5 - metabolism
• ISSN: 0165-2478; 1879-0542
• 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 viral replication. In particular, two individuals from this population whose CD4 + lymphocytes exhibited complete resistance to M-tropic viral 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 viral 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.