Hepatitis C virus core protein induces neuroimmune activation and potentiates Human Immunodeficiency Virus-1 neurotoxicity
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. Human mic...
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| Veröffentlicht in: | PloS one 2010-09, Vol.5 (9), p.e12856 |
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| creator | Vivithanaporn, Pornpun Maingat, Ferdinand Lin, Liang-Tzung Na, Hong Richardson, Christopher D Agrawal, Babita Cohen, Eric A Jhamandas, Jack H Power, Christopher |
| description | 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.
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.
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-1β, interleukin-6 and tumor necrosis factor-α in microglia (p |
| doi_str_mv | 10.1371/journal.pone.0012856 |
| format | Article |
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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.
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-1β, 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 β-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).
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.]]></description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0012856</identifier><identifier>PMID: 20877724</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Animal tissues ; Animals ; Apoptosis ; Astrocytes ; Astrocytes - cytology ; Astrocytes - immunology ; Autophagy ; Brain ; Brain research ; Cell culture ; Cell Line ; Cell survival ; Chemokines ; Core protein ; CXCL10 protein ; Cytokines ; Cytokines - immunology ; Dendritic cells ; Encephalitis ; Exposure ; Female ; Gene expression ; Genes ; Genetic engineering ; Genomes ; Genomics ; Gliosis ; Health aspects ; Hepacivirus - immunology ; Hepacivirus - physiology ; Hepatitis ; Hepatitis C ; Hepatitis C - complications ; Hepatitis C - immunology ; Hepatitis C - physiopathology ; Hepatitis C - virology ; Hepatitis C virus ; HIV ; HIV infections ; HIV Infections - complications ; HIV Infections - immunology ; HIV Infections - physiopathology ; HIV Infections - virology ; HIV-1 - immunology ; HIV-1 - physiology ; Human immunodeficiency virus ; Human performance ; Humans ; Immunology ; Immunology/Immune Response ; Immunoreactivity ; Implantation ; Implants ; Infection ; Infections ; Infectious Diseases/HIV Infection and AIDS ; Infectious Diseases/Infectious Diseases of the Nervous System ; Infectious Diseases/Viral Infections ; Infectivity ; Inflammation ; Interleukin 6 ; Interleukin 8 ; Interleukins ; Kinases ; Medical research ; Membrane currents ; Membrane proteins ; Mice ; Mice, Transgenic ; Microglia ; Microglia - cytology ; Microglia - immunology ; Molecular weight ; Neurodegeneration ; Neurology ; Neurons ; Neurons - cytology ; Neurons - immunology ; Neuropathogenesis ; Neuroscience/Animal Cognition ; Neuroscience/Cognitive Neuroscience ; Neuroscience/Neuronal and Glial Cell Biology ; Neurotoxicity ; Neutrophils ; Phagocytosis ; Proteins ; Ribonucleic acid ; RNA ; Studies ; TNF inhibitors ; Transgenic mice ; Tubulin ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Viral Core Proteins - immunology ; Viral proteins ; Viruses ; Vpr protein ; West Nile virus</subject><ispartof>PloS one, 2010-09, Vol.5 (9), p.e12856</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Vivithanaporn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Vivithanaporn et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c761t-3e96131ca8d3aa127ff02fdd7e9377f452635ab31d9ffcc4f91a02a49878d2cf3</citedby><cites>FETCH-LOGICAL-c761t-3e96131ca8d3aa127ff02fdd7e9377f452635ab31d9ffcc4f91a02a49878d2cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943470/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943470/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20877724$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vivithanaporn, Pornpun</creatorcontrib><creatorcontrib>Maingat, Ferdinand</creatorcontrib><creatorcontrib>Lin, Liang-Tzung</creatorcontrib><creatorcontrib>Na, Hong</creatorcontrib><creatorcontrib>Richardson, Christopher D</creatorcontrib><creatorcontrib>Agrawal, Babita</creatorcontrib><creatorcontrib>Cohen, Eric A</creatorcontrib><creatorcontrib>Jhamandas, Jack H</creatorcontrib><creatorcontrib>Power, Christopher</creatorcontrib><title>Hepatitis C virus core protein induces neuroimmune activation and potentiates Human Immunodeficiency Virus-1 neurotoxicity</title><title>PloS one</title><addtitle>PLoS One</addtitle><description><![CDATA[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.
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.
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-1β, 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 β-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).
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.]]></description><subject>Activation</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Astrocytes</subject><subject>Astrocytes - cytology</subject><subject>Astrocytes - immunology</subject><subject>Autophagy</subject><subject>Brain</subject><subject>Brain research</subject><subject>Cell culture</subject><subject>Cell Line</subject><subject>Cell survival</subject><subject>Chemokines</subject><subject>Core protein</subject><subject>CXCL10 protein</subject><subject>Cytokines</subject><subject>Cytokines - immunology</subject><subject>Dendritic cells</subject><subject>Encephalitis</subject><subject>Exposure</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic engineering</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Gliosis</subject><subject>Health aspects</subject><subject>Hepacivirus - immunology</subject><subject>Hepacivirus - physiology</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C - complications</subject><subject>Hepatitis C - immunology</subject><subject>Hepatitis C - physiopathology</subject><subject>Hepatitis C - virology</subject><subject>Hepatitis C virus</subject><subject>HIV</subject><subject>HIV infections</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - physiopathology</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - immunology</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Human performance</subject><subject>Humans</subject><subject>Immunology</subject><subject>Immunology/Immune Response</subject><subject>Immunoreactivity</subject><subject>Implantation</subject><subject>Implants</subject><subject>Infection</subject><subject>Infections</subject><subject>Infectious Diseases/HIV Infection and AIDS</subject><subject>Infectious Diseases/Infectious Diseases of the Nervous System</subject><subject>Infectious Diseases/Viral Infections</subject><subject>Infectivity</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Interleukin 8</subject><subject>Interleukins</subject><subject>Kinases</subject><subject>Medical research</subject><subject>Membrane currents</subject><subject>Membrane proteins</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Microglia</subject><subject>Microglia - cytology</subject><subject>Microglia - immunology</subject><subject>Molecular weight</subject><subject>Neurodegeneration</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neurons - cytology</subject><subject>Neurons - immunology</subject><subject>Neuropathogenesis</subject><subject>Neuroscience/Animal Cognition</subject><subject>Neuroscience/Cognitive Neuroscience</subject><subject>Neuroscience/Neuronal and Glial Cell Biology</subject><subject>Neurotoxicity</subject><subject>Neutrophils</subject><subject>Phagocytosis</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Studies</subject><subject>TNF inhibitors</subject><subject>Transgenic mice</subject><subject>Tubulin</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Viral Core Proteins - immunology</subject><subject>Viral proteins</subject><subject>Viruses</subject><subject>Vpr protein</subject><subject>West Nile virus</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2LEzEYhQdR3HX1H4gGBMGL1kkyM0luFpaitrCw4MfehjQfbZaZZEwyZeuvN7WzSwcUJBcJb55zEg6nKF7Dcg4xgR_v_BCcaOe9d3pelhDRunlSnEOG0axBJX56cj4rXsR4V5Y1pk3zvDhDJSWEoOq8-LXUvUg22QgWYGfDEIH0QYM--KStA9apQeoInB6Ct103OA2ETHaXRd4B4RToM-mSFSljy6ETDqwOnFfaWGm1k3twezCewaNL8vd5nvYvi2dGtFG_GveL4sfnT98Xy9n1zZfV4up6JkkD0wxr1kAMpaAKCwERMaZERimiGSbEVDVqcC3WGCpmjJSVYVCUSFSMEqqQNPiieHv07Vsf-Rhb5BAxVDWEUpiJ1ZFQXtzxPthOhD33wvI_Ax82XIRkZas5gYYSrDGRqq5UrSjTFFZrqbA2eE1Z9rocXxvWnVYyRxNEOzGd3ji75Ru_44hVuCJlNng3GgT_c9Ax_ePLI7UR-VfWGZ_NZGej5FcVwbRmCDaZmv-FykvpzspcHGPzfCL4MBFkJun7tBFDjHz17ev_sze3U_b9CbvVok3b6NvhUKI4BasjKIOPMWjzmBws-aH3D2nwQ-_52Psse3Oa-qPooej4N1yEAQg</recordid><startdate>20100921</startdate><enddate>20100921</enddate><creator>Vivithanaporn, Pornpun</creator><creator>Maingat, Ferdinand</creator><creator>Lin, Liang-Tzung</creator><creator>Na, Hong</creator><creator>Richardson, Christopher D</creator><creator>Agrawal, Babita</creator><creator>Cohen, Eric A</creator><creator>Jhamandas, Jack H</creator><creator>Power, Christopher</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20100921</creationdate><title>Hepatitis C virus core protein induces neuroimmune activation and potentiates Human Immunodeficiency Virus-1 neurotoxicity</title><author>Vivithanaporn, Pornpun ; Maingat, Ferdinand ; Lin, Liang-Tzung ; Na, Hong ; Richardson, Christopher D ; Agrawal, Babita ; Cohen, Eric A ; Jhamandas, Jack H ; Power, Christopher</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c761t-3e96131ca8d3aa127ff02fdd7e9377f452635ab31d9ffcc4f91a02a49878d2cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Activation</topic><topic>Animal tissues</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Astrocytes</topic><topic>Astrocytes - cytology</topic><topic>Astrocytes - immunology</topic><topic>Autophagy</topic><topic>Brain</topic><topic>Brain research</topic><topic>Cell culture</topic><topic>Cell Line</topic><topic>Cell survival</topic><topic>Chemokines</topic><topic>Core protein</topic><topic>CXCL10 protein</topic><topic>Cytokines</topic><topic>Cytokines - immunology</topic><topic>Dendritic cells</topic><topic>Encephalitis</topic><topic>Exposure</topic><topic>Female</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic engineering</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Gliosis</topic><topic>Health aspects</topic><topic>Hepacivirus - immunology</topic><topic>Hepacivirus - physiology</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Hepatitis C - complications</topic><topic>Hepatitis C - immunology</topic><topic>Hepatitis C - physiopathology</topic><topic>Hepatitis C - virology</topic><topic>Hepatitis C virus</topic><topic>HIV</topic><topic>HIV infections</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - physiopathology</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - immunology</topic><topic>HIV-1 - physiology</topic><topic>Human immunodeficiency virus</topic><topic>Human performance</topic><topic>Humans</topic><topic>Immunology</topic><topic>Immunology/Immune Response</topic><topic>Immunoreactivity</topic><topic>Implantation</topic><topic>Implants</topic><topic>Infection</topic><topic>Infections</topic><topic>Infectious Diseases/HIV Infection and AIDS</topic><topic>Infectious Diseases/Infectious Diseases of the Nervous System</topic><topic>Infectious Diseases/Viral Infections</topic><topic>Infectivity</topic><topic>Inflammation</topic><topic>Interleukin 6</topic><topic>Interleukin 8</topic><topic>Interleukins</topic><topic>Kinases</topic><topic>Medical research</topic><topic>Membrane currents</topic><topic>Membrane proteins</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Microglia</topic><topic>Microglia - cytology</topic><topic>Microglia - immunology</topic><topic>Molecular weight</topic><topic>Neurodegeneration</topic><topic>Neurology</topic><topic>Neurons</topic><topic>Neurons - cytology</topic><topic>Neurons - immunology</topic><topic>Neuropathogenesis</topic><topic>Neuroscience/Animal Cognition</topic><topic>Neuroscience/Cognitive Neuroscience</topic><topic>Neuroscience/Neuronal and Glial Cell Biology</topic><topic>Neurotoxicity</topic><topic>Neutrophils</topic><topic>Phagocytosis</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Studies</topic><topic>TNF inhibitors</topic><topic>Transgenic mice</topic><topic>Tubulin</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><topic>Viral Core Proteins - immunology</topic><topic>Viral proteins</topic><topic>Viruses</topic><topic>Vpr protein</topic><topic>West Nile virus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vivithanaporn, Pornpun</creatorcontrib><creatorcontrib>Maingat, Ferdinand</creatorcontrib><creatorcontrib>Lin, Liang-Tzung</creatorcontrib><creatorcontrib>Na, Hong</creatorcontrib><creatorcontrib>Richardson, Christopher D</creatorcontrib><creatorcontrib>Agrawal, Babita</creatorcontrib><creatorcontrib>Cohen, Eric A</creatorcontrib><creatorcontrib>Jhamandas, Jack H</creatorcontrib><creatorcontrib>Power, Christopher</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vivithanaporn, Pornpun</au><au>Maingat, Ferdinand</au><au>Lin, Liang-Tzung</au><au>Na, Hong</au><au>Richardson, Christopher D</au><au>Agrawal, Babita</au><au>Cohen, Eric A</au><au>Jhamandas, Jack H</au><au>Power, Christopher</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatitis C virus core protein induces neuroimmune activation and potentiates Human Immunodeficiency Virus-1 neurotoxicity</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-09-21</date><risdate>2010</risdate><volume>5</volume><issue>9</issue><spage>e12856</spage><pages>e12856-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract><![CDATA[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.
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.
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-1β, 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 β-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).
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.]]></abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20877724</pmid><doi>10.1371/journal.pone.0012856</doi><tpages>e12856</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2010-09, Vol.5 (9), p.e12856 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1292467881 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Activation Animal tissues Animals Apoptosis Astrocytes Astrocytes - cytology Astrocytes - immunology Autophagy Brain Brain research Cell culture Cell Line Cell survival Chemokines Core protein CXCL10 protein Cytokines Cytokines - immunology Dendritic cells Encephalitis Exposure Female Gene expression Genes Genetic engineering Genomes Genomics Gliosis Health aspects Hepacivirus - immunology Hepacivirus - physiology Hepatitis Hepatitis C Hepatitis C - complications Hepatitis C - immunology Hepatitis C - physiopathology Hepatitis C - virology Hepatitis C virus HIV HIV infections HIV Infections - complications HIV Infections - immunology HIV Infections - physiopathology HIV Infections - virology HIV-1 - immunology HIV-1 - physiology Human immunodeficiency virus Human performance Humans Immunology Immunology/Immune Response Immunoreactivity Implantation Implants Infection Infections Infectious Diseases/HIV Infection and AIDS Infectious Diseases/Infectious Diseases of the Nervous System Infectious Diseases/Viral Infections Infectivity Inflammation Interleukin 6 Interleukin 8 Interleukins Kinases Medical research Membrane currents Membrane proteins Mice Mice, Transgenic Microglia Microglia - cytology Microglia - immunology Molecular weight Neurodegeneration Neurology Neurons Neurons - cytology Neurons - immunology Neuropathogenesis Neuroscience/Animal Cognition Neuroscience/Cognitive Neuroscience Neuroscience/Neuronal and Glial Cell Biology Neurotoxicity Neutrophils Phagocytosis Proteins Ribonucleic acid RNA Studies TNF inhibitors Transgenic mice Tubulin Tumor necrosis factor-TNF Tumor necrosis factor-α Viral Core Proteins - immunology Viral proteins Viruses Vpr protein West Nile virus |
| title | Hepatitis C virus core protein induces neuroimmune activation and potentiates Human Immunodeficiency Virus-1 neurotoxicity |
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