Expression of simian immunodeficiency virus Nef protein in CD4+ T cells leads to a molecular profile of viral persistence and immune evasion.
The Nef protein of human immunodeficiency virus and simian immunodeficiency virus is expressed early in infection and plays an important role in disease progression in vivo. In addition, Nef has been shown to modulate cellular functions. To decipher Nef-mediated changes in gene expression, we utilized DNA microarray analysis to elucidate changes in gene expression in a Jurkat CD4+ T-cell line stably expressing SIV-Nef protein under the control of an inducible promoter. Our results showed that genes associated with antigen presentation including members of the T-cell receptor and major histocompatibility class 1 complex were consistently down-regulated at the transcript level in SIV-Nef-expressing cells. In addition, Nef induced a transcriptional profile of cell-cycle-related genes that support the survival of Nef-expressing cells. Furthermore, Nef enhanced the transcription of genes encoding enzymes and factors that catalyze the biosynthesis of membrane glycolipids and phospholipids. In conclusion, gene expression profiling showed that SIV-Nef induces a transcriptional profile in CD4+ T cells that promotes immune evasion and cell survival, thus facilitating viral persistence.
Ndolo
Thomas
T
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616, USA.
George
Michael
M
Nguyen
Hau
H
Dandekar
Satya
S
D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D002453:Cell Cycle / Q000235:genetics; D005786:Gene Expression Regulation; D006017:Glycolipids / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D006017:Glycolipids; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins