Human immunodeficiency virus (HIV) type 1 Vpr induces differential regulation of T cell costimulatory molecules: direct effect of Vpr on T cell activation and immune function.
Human immunodeficiency virus type 1 (HIV-1) viral proteins disrupt the normal host cellular immune pathways thus exploiting the cellular machinery for replication, survival and to escape host immune attack. Here we evaluated the direct effects of HIV-1 Vpr-mediated immune modulation of infected T cells. Vpr specifically downregulated the expression of CD28 and increased the expression of CTLA-4, whereas no significant difference in the expression of CD25 and HLA-DR was observed. Interferon gamma (IFN-gamma) production in T cells was evaluated as a measure of the downstream effector functions. Results indicate that Vpr significantly inhibited IFN-gamma production and this may, in part, due to Vpr's ability to inhibit the nuclear translocation of NF-kappaB, and its transcriptional regulation. Together these results support that HIV-1 Vpr selectively dysregulates the immune functions at multiple levels and exerts its inhibitory effects in the presence of other viral proteins.
Venkatachari
Narasimhan J
NJ
Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, 130 Desoto Street, Pittsburgh, PA 15261, USA.
Majumder
Biswanath
B
Ayyavoo
Velpandi
V
D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D060908:CTLA-4 Antigen; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016336:Gene Products, vpr / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016336:Gene Products, vpr; D016328:NF-kappa B; D054325:vpr Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma