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Down‐modulation of the ZAP‐70 protein tyrosine kinase in macaque T lymphocytes infected with SIVsmmPBj14
Author(s) -
Thai ToHa,
Fultz Patricia N.
Publication year - 1998
Publication title -
journal of medical primatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.31
H-Index - 42
eISSN - 1600-0684
pISSN - 0047-2565
DOI - 10.1111/j.1600-0684.1998.tb00238.x
Subject(s) - simian immunodeficiency virus , biology , macaque , peripheral blood mononuclear cell , downregulation and upregulation , cd8 , virology , spleen , t cell , immunology , in vitro , virus , microbiology and biotechnology , immune system , paleontology , biochemistry , gene
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‐PBj14. 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.