Downregulation of CCR5 on activated CD4 T cells in HIV-infected Indians.
BACKGROUND
HIV infection in India is unique as it occurs predominantly by CCR5-utilizing isolates that exhibit no co-receptor switch.


OBJECTIVE
To study HIV-1 co-receptor dynamics on T cells and monocytes following viral infection.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Dubey
Shweta
S
Virology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi 110067, India.
Khalid
Mohammad
M
Wesley
Clement
C
Khan
Samir Ali
SA
Wanchu
Ajay
A
Jameel
Shahid
S
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015536:Down-Regulation; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007194:India; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; C514793:gp120 protein, Human immunodeficiency virus 1; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1