Human immunodeficiency virus type 1 Vpr impairs dendritic cell maturation and T-cell activation: implications for viral immune escape.
Antigen presentation and T-cell activation are dynamic processes involving signaling molecules present in both APCs and T cells. Effective APC function and T-cell activation can be compromised by viral immune evasion strategies, including those of human immunodeficiency virus type 1 (HIV-1). In this study, we determined the effects of HIV-1 Vpr on one of the initial target of the virus, dendritic cells (DC), by investigating DC maturation, cytokine profiling, and CD8-specific T-cell stimulation function followed by a second signal. Vpr impaired the expression of CD80, CD83, and CD86 at the transcriptional level without altering normal cellular transcription. Cytokine profiling indicated that the presence of Vpr inhibited production of interleukin 12 (IL-12) and upregulated IL-10, whereas IL-6 and IL-1beta were unaltered. Furthermore, DC infected with HIV-1 vpr+ significantly reduced the activation of antigen-specific memory and recall cytotoxic-T-lymphocyte responses. Taken together, these results indicate that HIV-1 Vpr may in part be responsible for HIV-1 immune evasion by inhibiting the maturation of costimulatory molecules and cytokines essential for immune activation.
Majumder
Biswanath
B
Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, 130 Desoto Street, Pittsburgh, Pennsylvania 15261, USA.
Janket
Michelle L
ML
Schafer
Elizabeth A
EA
Schaubert
Keri
K
Huang
Xiao-Li
XL
Kan-Mitchell
June
J
Rinaldo
Charles R
CR
Ayyavoo
Velpandi
V
D015703:Antigens, CD / Q000235:genetics; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016336:Gene Products, vpr / Q000494:pharmacology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014158:Transcription, Genetic; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015703:Antigens, CD; D016207:Cytokines; D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus