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 Scopus citations

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

ASJC Scopus subject areas

  • Immunology

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    Bostik, P., Wu, P., Dodd, G. L., Villinger, F., Mayne, A. E., Bostik, V., Grimm, B. D., Robinson, D., Kung, H-J., & Ansari, A. A. (2001). Identification of protein kinases dysregulated in CD4+ T cells in pathogenic versus apathogenic simian immunodeficiency virus infection. Journal of Virology, 75(23), 11298-11306. https://doi.org/10.1128/JVI.75.23.11298-11306.2001