TY - JOUR
T1 - Hepatitis C virus core protein induces neuroimmune activation and potentiates human immunodeficiency virus-1 neurotoxicity
AU - Vivithanaporn, Pornpun
AU - Maingat, Ferdinand
AU - Lin, Liang Tzung
AU - Na, Hong
AU - Richardson, Christopher D.
AU - Agrawal, Babita
AU - Cohen, Éric A.
AU - Jhamandas, Jack H.
AU - Power, Christopher
PY - 2010
Y1 - 2010
N2 - Background: 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
AB - Background: 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
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U2 - 10.1371/journal.pone.0012856
DO - 10.1371/journal.pone.0012856
M3 - Article
AN - SCOPUS:77958458743
VL - 5
SP - 1
EP - 14
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 9
M1 - e12856
ER -