Down-modulation of the ZAP-70 protein tyrosine kinase in macaque T lymphocytes infected with SIVsmmPBj14.
The simian immunodeficiency virus SIV-PBj14 is the most virulent primate lentivirus identified to date. Other SIV strains, including the parental SIVsmm9, require mitogen-activated peripheral blood mononuclear cells (PBMC) for replication in vitro; however, SIV-PBj14 replicates in quiescent pig-tailed macaque PBMC and induces cellular proliferation, consistent with its in vivo pathogenesis. To identify mechanisms involved in SIV-PBj14-induced T-cell proliferation, kinases important in early T-cell receptor-mediated activation pathways were studied. Immunoblot analyses showed that ZAP-70 protein, a tyrosine kinase, was downregulated, primarily in CD8+ T cells, as early as 30 minutes after in vitro infection of quiescent macaque PBMC with SIV-PBj 14. Furthermore, this downregulation required the presence of either CD4+ T cells or adherent cells or both cell populations. In agreement with the in vitro results, ZAP-70 expression was downregulated in macaque PBMC, spleen, and rectal lymph node cells as early as 2 days after rectal inoculation of pig-tailed macaques with SIV-PBj14. This phenomenon, however, was not observed in cells obtained from distal lymph nodes to which the virus had not disseminated, implying that the presence of SIV-PBj14 is necessary to induce downregulation of ZAP-70.
Thai
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Department of Microbiology, University of Alabama School of Medicine, Birmingham 35294, USA.
Fultz
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D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000821:virology; D015971:Gene Expression Regulation, Enzymologic; D015750:Genes, gag; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D008254:Macaca nemestrina; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013154:Spleen / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000821:virology*; D051746:ZAP-70 Protein-Tyrosine Kinase
D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase