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dc.contributor.authorPornpun Vivithanapornen_US
dc.contributor.authorFerdinand Maingaten_US
dc.contributor.authorLiang Tzung Linen_US
dc.contributor.authorHong Naen_US
dc.contributor.authorChristopher D. Richardsonen_US
dc.contributor.authorBabita Agrawalen_US
dc.contributor.authorÉric A. Cohenen_US
dc.contributor.authorJack H. Jhamandasen_US
dc.contributor.authorChristopher Poweren_US
dc.contributor.otherUniversity of Albertaen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherDalhousie Universityen_US
dc.contributor.otherInstitut de Recherches Cliniques de Montrealen_US
dc.date.accessioned2018-09-24T08:37:18Z-
dc.date.available2018-09-24T08:37:18Z-
dc.date.issued2010-10-29en_US
dc.identifier.citationPLoS ONE. Vol.5, No.9 (2010), 1-14en_US
dc.identifier.issn19326203en_US
dc.identifier.other2-s2.0-77958458743en_US
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77958458743&origin=inwarden_US
dc.identifier.urihttp://repository.li.mahidol.ac.th/dspace/handle/123456789/28443-
dc.description.abstractBackground: Hepatitis C virus (HCV) genomes and proteins are present in human brain tissues although the impact of HIV/ HCV co-infection on neuropathogenesis remains unclear. Herein, we investigate HCV infectivity and effects on neuronal survival and neuroinflammation in conjunction with HIV infection. Methodology: Human microglia, astrocyte and neuron cultures were infected with cell culture-derived HCV or exposed to HCV core protein with or without HIV-1 infection or HIV-1 Viral Protein R (Vpr) exposure. Host immune gene expression and cell viability were measured. Patch-clamp studies of human neurons were performed in the presence or absence of HCV core protein. Neurobehavioral performance and neuropathology were examined in HIV-1 Vpr-transgenic mice in which stereotaxic intrastriatal implants of HCV core protein were performed. Principal Findings: HCV-encoded RNA as well as HCV core and non-structural 3 (NS3) proteins were detectable in human microglia and astrocytes infected with HCV. HCV core protein exposure induced expression of pro-inflammatory cytokines including interleukin-1b, interleukin-6 and tumor necrosis factor-α in microglia (p<0.05) but not in astrocytes while increased chemokine (e.g. CXCL10 and interleukin-8) expression was observed in both microglia and astrocytes (p<0.05). HCV core protein modulated neuronal membrane currents and reduced both β-III-tubulin and lipidated LC3-II expression (p<0.05). Neurons exposed to supernatants from HCV core-activated microglia exhibited reduced b-III-tubulin expression (p<0.05). HCV core protein neurotoxicity and interleukin-6 induction were potentiated by HIV-1 Vpr protein (p<0.05). HIV-1 Vpr transgenic mice implanted with HCV core protein showed gliosis, reduced neuronal counts together with diminished LC3 immunoreactivity. HCV core-implanted animals displayed neurobehavioral deficits at days 7 and 14 post-implantation (p<0.05). Conclusions: HCV core protein exposure caused neuronal injury through suppression of neuronal autophagy in addition to neuroimmune activation. The additive neurotoxic effects of HCV-and HIV-encoded proteins highlight extrahepatic mechanisms by which HCV infection worsens the disease course of HIV infection. © 2010 Vivithanaporn et al.en_US
dc.rightsMahidol Universityen_US
dc.source.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77958458743&origin=inwarden_US
dc.subjectAgricultural and Biological Sciencesen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.titleHepatitis C virus core protein induces neuroimmune activation and potentiates human immunodeficiency virus-1 neurotoxicityen_US
dc.typeArticleen_US
dc.rights.holderSCOPUSen_US
dc.identifier.doi10.1371/journal.pone.0012856en_US
Appears in Collections:Scopus 2006-2010

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