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

被引:17
作者
Bostik, P
Wu, P
Dodd, GL
Villinger, F
Mayne, AE
Bostik, V
Grimm, BD
Robinson, D
Kung, HJ
Ansari, AA
机构
[1] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
[2] Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA
关键词
D O I
10.1128/JVI.75.23.11298-11306.2001
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human immunodeficiency virus infection in humans and simian immunodeficiency virus (SA) 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 Lek 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 SAI, showed chronic downregulation of baseline expression of MLK-3, 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 RNI (but not SIV-infected SM) led to the repression of CaMKK beta 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.
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页码:11298 / 11306
页数:9
相关论文
共 58 条
[1]   Defective survival and activation of thymocytes in transgenic mice expressing a catalytically inactive form of Ca2+/calmodulin-dependent protein kinase IV [J].
Anderson, KA ;
Ribar, TJ ;
Illario, M ;
Means, AR .
MOLECULAR ENDOCRINOLOGY, 1997, 11 (06) :725-737
[2]   The physical association and phosphorylation of Cdc25C protein phosphatase by Prk [J].
Bin, OY ;
Li, WQ ;
Pan, HQ ;
Meadows, J ;
Hoffmann, I ;
Dai, W .
ONCOGENE, 1999, 18 (44) :6029-6036
[3]   Human prk is a conserved protein serine/threonine kinase involved in regulating M phase functions [J].
Bin, OY ;
Pan, HQ ;
Lu, L ;
Li, J ;
Stambrook, P ;
Li, B ;
Dai, W .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (45) :28646-28651
[4]   Extracellular HIV-1 Tat protein induces a rapid and selective activation of protein kinase C (PKC)-α, -ε, and -ζ isoforms in PC12 cells [J].
Borgatti, P ;
Zauli, G ;
Cantley, LC ;
Capitani, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1998, 242 (02) :332-337
[5]   Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4(+) T lymphoblastoid Jurkat cells [J].
Borgatti, P ;
Zauli, G ;
Colamussi, ML ;
Gibellini, D ;
Previati, M ;
Cantley, LL ;
Capitani, S .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (11) :2805-2811
[6]   Relative resistance in the development of T cell anergy in CD4+ T cells from simian immunodeficiency virus disease-resistant sooty mangabeys [J].
Bostik, P ;
Mayne, AE ;
Villinger, F ;
Greenberg, KP ;
Powell, JD ;
Ansari, AA .
JOURNAL OF IMMUNOLOGY, 2001, 166 (01) :506-516
[7]  
Bostik P, 2000, J ACQ IMMUN DEF SYND, V24, P89
[8]   Detection of intracellular signal transduction molecules in PBMC from rhesus macaques and sooty mangabeys [J].
Brice, GT ;
Villinger, F ;
Mayne, A ;
Sundstrom, JB ;
Ansari, AA .
JOURNAL OF MEDICAL PRIMATOLOGY, 1996, 25 (03) :210-217
[9]   Development of an animal model for autotransfusion therapy: In vitro characterization and analysis of anti-CD3/CD28 expanded cells [J].
Brice, GT ;
Riley, JL ;
Villinger, F ;
Mayne, A ;
Hillyer, CD ;
June, CH ;
Ansari, AA .
JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY, 1998, 19 (03) :210-220
[10]   T cell antigen receptor signal transduction pathways [J].
Cantrell, D .
ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :259-274