Hepatitis C virus core protein induces neuroimmune activation and potentiates human immunodeficiency virus-1 neurotoxicity

Pornpun Vivithanaporn, Ferdinand Maingat, Liang Tzung Lin, Hong Na, Christopher D. Richardson, Babita Agrawal, Éric A. Cohen, Jack H. Jhamandas, Christopher Power

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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

Original languageEnglish
Article numbere12856
Pages (from-to)1-14
Number of pages14
JournalPLoS One
Volume5
Issue number9
DOIs
Publication statusPublished - 2010
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Vivithanaporn, P., Maingat, F., Lin, L. T., Na, H., Richardson, C. D., Agrawal, B., Cohen, É. A., Jhamandas, J. H., & Power, C. (2010). Hepatitis C virus core protein induces neuroimmune activation and potentiates human immunodeficiency virus-1 neurotoxicity. PLoS One, 5(9), 1-14. [e12856]. https://doi.org/10.1371/journal.pone.0012856