Downregulation of CCR5 on activated CD4 T cells in HIV-infected Indians
Dubey, S.; Khalid, M.; Wesley, C.; Khan, S.A.; Wanchu, A.; Jameel, S.
Journal of Clinical Virology the Official Publication of the Pan American Society for Clinical Virology 43(1): 25-31
2008
ISSN/ISBN: 1386-6532 PMID: 18462992 DOI: 10.1016/j.jcv.2008.03.026Document Number: 202893
HIV infection in India is unique as it occurs predominantly by CCR5-utilizing isolates that exhibit no co-receptor switch. To study HIV-1 co-receptor dynamics on T cells and monocytes following viral infection. HIV co-receptor expression was evaluated by flow cytometry on various cell subsets in HIV-infected Indians and in vitro in human peripheral blood mononuclear cells infected with CCR5- or CXCR4-utilizing HIV-1. Transfection of the T cell line CEM-CCR5 (which expresses CD4, CCR5 and CXCR4) with HIV-1 Nef or Vpu expression vectors, or treatment with recombinant soluble gp120 from CCR5- and CXCR4-tropic HIV-1, was carried out to determine their effects on co-receptor expression. Indian HIV patients had fewer CD4+CCR5+ T cells and CCR5-expressing activated CD4+ T cells, but higher CXCR4-expressing activated CD4+ T cells compared with controls. Expression of CCR5 was not different on monocytes in HIV patients as compared to controls. The CCR5 downregulation on T cells was HIV infection specific and was governed by the co-receptor-utilization phenotype of the virus. The Nef and soluble gp120 proteins induced CCR5 downregulation, the latter in a co-receptor-utilization phenotype specific manner. The HIV-1 co-receptor dynamics in Indian patients is distinct from western patients and depends upon the virus surface protein. We propose this to be a viral survival strategy.
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