Apoptotic Effects of a Chimeric Plant Virus Carrying a Mimotope of the Hepatitis C virus Hypervariable Region 1: Role of Caspases and Endoplasmic Reticulum-Stress
Autor: | Giuseppina Piazzolla, Nicola Napoli, M. Schiavone, Antonella Vitti, Maria Nuzzaci, Cosimo Tortorella, Pasquale Piazzolla, Salvatore Antonaci |
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Rok vydání: | 2012 |
Předmět: |
Adult
Male Hepatitis C virus Immunology Apoptosis Hepacivirus Biology medicine.disease_cause Cucumovirus Article Cucumber mosaic virus Epitopes Viral Proteins medicine Humans Immunology and Allergy Endoplasmic Reticulum Chaperone BiP Caspase 12 Cells Cultured Aged Caspase 8 cucumber mosaic virus Mimotope Molecular Mimicry virus diseases Hepatitis C Chronic Middle Aged Endoplasmic Reticulum Stress Virology Molecular biology Caspase 9 Hypervariable region NS2-3 protease Molecular mimicry caspases HCV DNA Viral Leukocytes Mononuclear Unfolded protein response ER-stress Female |
Zdroj: | Journal of Clinical Immunology |
ISSN: | 1573-2592 0271-9142 |
DOI: | 10.1007/s10875-012-9676-1 |
Popis: | The role of apoptosis in the persistence of hepatitis C virus (HCV) infection is controversial. Moreover, conflicting data on the modulation of this process by HCV proteins have been provided. We evaluated the susceptibility of peripheral lymphocytes from patients with chronic hepatitis C to apoptosis both spontaneous and after incubation with a chimeric Cucumber mosaic virus (CMV) carrying 180 copies of the synthetic R9 mimotope obtained from more than 200 hypervariable region-1 sequences of HCV. Resting T lymphocytes were found to be sensitized to apoptosis as a result of chronic HCV infection. The plant virus-derived vector R9-CMV displayed a strong pro-apoptotic effect associated with activation of both caspase-8 and -9, indicating the involvement of both extrinsic and intrinsic apoptotic pathways. A parallel R9-CMV-mediated activation of endoplasmic reticulum-stress was suggested by the significant induction of BiP/GRP78, GADD153 and caspase-12. These data contribute to define the complex HCV/host interaction, and open new prospects for developing a plant-derived antigen-presenting system to strengthen host defences against persistent pathogens. |
Databáze: | OpenAIRE |
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