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The Hepatitis C Vir...
The Hepatitis C Virus Core Protein Modulates T Cell Responses by Inducing Spontaneous and Altering T-cell Receptor-triggered Ca2+ Oscillations
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- Bergqvist, Anders (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Anders Bergqvist
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- Sundström, Sara (author)
- Karolinska Institutet
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- Dimberg, Lina Y. (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Gylfe, Erik (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Masucci, Maria G. (author)
- Karolinska Institutet
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(creator_code:org_t)
- ASBMB, 2003
- 2003
- English.
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In: Journal of Biological Chemistry. - : ASBMB. - 0021-9258 .- 1083-351X. ; 278:21, s. 18877-18883
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Alterations of cytokine responses are thought to favor the establishment of persistent hepatitis C virus (HCV) infection, enhancing the risk of liver cirrhosis and hepatocellular carcinoma. Expression of the HCV core (C) protein modulates transcription of the IL-2 promoter in T lymphocytes by activating the nuclear factor of activated T lymphocyte (NFAT) pathway. Here we report on the effect of HCV C on Ca2+ signaling, which is essential for activation of NFAT. Expression of HCV C correlated with increased levels of cytosolic Ca2+ and spontaneous Ca2+ oscillations in transfected Jurkat cells. Triggering of the T-cell receptor induced a prolonged Ca2+ response characterized by vigorous high frequent oscillations in a high proportion of the responding cells. This was associated with decreased sizes and accelerated emptying of the intracellular calcium stores. The effect of HCV C on calcium mobilization was not dependent on phospholipase C-1 (PLC-) activity or increased inositol 1,4,5-trisphosphate (IP3) production and did not require functional IP3 receptors, suggesting that insertion of the viral protein in the endoplasmic reticulum membrane may be sufficient to promote Ca2+ leakage with dramatic downstream consequences on the magnitude and duration of the response. Our data suggest that expression of HCV C in infected T lymphocytes may contribute to the establishment of persistent infections by inducing Ca2+ oscillations that regulate both the efficacy and information content of Ca2+ signals and are ultimately responsible for induction of gene expression and functional differentiation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- Medical cell biology
- Medicinsk cellbiologi
- Virology
- Virologi
- Medical Cell Biology
- Medicinsk cellbiologi
- Medical Virology
- Medicinsk virologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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