Identification of protein kinases dysregulated in CD4+ T cells in pathogenic versus apathogenic simian immunodeficiency virus infection

P. Bostik, P. Wu, G. L. Dodd, F. Villinger, A. E. Mayne, V. Bostik, B. D. Grimm, D. Robinson, Hsing-Jien Kung, A. A. Ansari

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Human immunodeficiency virus infection in humans and simian immunodeficiency virus (SIV) infection in rhesus macaques (RM) leads to a generalized loss of immune responses involving perturbations in T-cell receptor (TCR) signaling. In contrast, naturally SIV-infected sooty mangabeys (SM) remain asymptomatic and retain immune responses despite relatively high viral loads. However, SIV infection in both RM and SM led to similar decreases in TCR-induced Lck phosphorylation. In this study, a protein tyrosine kinase (PTK) differential display method was utilized to characterize the effects of in vivo SIV infection on key signaling molecules of the CD4+ T-cell signaling pathways. The CD4+ T cells from SIV-infected RM, but not SIV-infected SM, showed chronic downregulation of baseline expression of MLK3, PRK, and GSK3, and symptomatically SIV-infected RM showed similar downregulation of MKK3. In vitro TCR stimulation with or without CD28 costimulation of CD4+ T cells did not lead to the enhancement of gene transcription of these PTKs. While the CD4+ T cells from SIV-infected RM showed a significant increase of the baseline and anti-TCR-mediated ROR2 transcription, SIV infection in SM led to substantially decreased anti-TCR-stimulated ROR2 transcription. TCR stimulation of CD4+ T cells from SIV-infected RM (but not SIV-infected SM) led to the repression of CaMKKβ and the induction of gene transcription of MLK2. Studies of the function of these molecules in T-cell signaling may lead to the identification of potential targets for specific intervention, leading to the restoration of T-cell responses.

Original languageEnglish (US)
Pages (from-to)11298-11306
Number of pages9
JournalJournal of Virology
Volume75
Issue number23
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
Virus Diseases
protein kinases
Protein Kinases
T-lymphocytes
Cercocebus atys
T-Lymphocytes
T-Cell Antigen Receptor
Macaca mulatta
Cercocebus
infection
receptors
transcription (genetics)
Calcium-Calmodulin-Dependent Protein Kinase Kinase
Down-Regulation
HIV
CD4 Antigens
immune response
protein-tyrosine kinases

ASJC Scopus subject areas

  • Immunology

Cite this

Identification of protein kinases dysregulated in CD4+ T cells in pathogenic versus apathogenic simian immunodeficiency virus infection. / Bostik, P.; Wu, P.; Dodd, G. L.; Villinger, F.; Mayne, A. E.; Bostik, V.; Grimm, B. D.; Robinson, D.; Kung, Hsing-Jien; Ansari, A. A.

In: Journal of Virology, Vol. 75, No. 23, 2001, p. 11298-11306.

Research output: Contribution to journalArticle

Bostik, P, Wu, P, Dodd, GL, Villinger, F, Mayne, AE, Bostik, V, Grimm, BD, Robinson, D, Kung, H-J & Ansari, AA 2001, 'Identification of protein kinases dysregulated in CD4+ T cells in pathogenic versus apathogenic simian immunodeficiency virus infection', Journal of Virology, vol. 75, no. 23, pp. 11298-11306. https://doi.org/10.1128/JVI.75.23.11298-11306.2001
Bostik, P. ; Wu, P. ; Dodd, G. L. ; Villinger, F. ; Mayne, A. E. ; Bostik, V. ; Grimm, B. D. ; Robinson, D. ; Kung, Hsing-Jien ; Ansari, A. A. / Identification of protein kinases dysregulated in CD4+ T cells in pathogenic versus apathogenic simian immunodeficiency virus infection. In: Journal of Virology. 2001 ; Vol. 75, No. 23. pp. 11298-11306.
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