OAS Gene Family Expression Is Associated with HIV-Related Neurocognitive Disorders
HIV-associated neurocognitive disorders are common in HIV-infected individuals, even in the combination antiretroviral therapy (c-ART) era. Several mechanisms are involved in neuronal damage, including chronic inflammation immune activation. Mammalian 2′-5′-oligoadenylate synthetase (OAS) genes are...
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| Veröffentlicht in: | Molecular neurobiology 2018-03, Vol.55 (3), p.1905-1914 |
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| creator | Sanfilippo, C. Pinzone, M.R. Cambria, D. Longo, A. Palumbo, M. Di Marco, R. Condorelli, F. Nunnari, G. Malaguarnera, L. Di Rosa, M. |
| description | HIV-associated neurocognitive disorders are common in HIV-infected individuals, even in the combination antiretroviral therapy (c-ART) era. Several mechanisms are involved in neuronal damage, including chronic inflammation immune activation. Mammalian 2′-5′-oligoadenylate synthetase (OAS) genes are produced in response to interferon (IFN), mainly by monocytes, and exert their antiviral functions by activation of RNase L that degrades viral and cellular RNAs. In this study, we aimed at exploring OAS gene family RNA expression in simian immunodeficiency virus encephalitis (SIVE), in HIV-associated neurocognitive disorders (HAND), and in HIV-associate dementia (HAD). We analyzed three microarray datasets obtained from the NCBI in order to assess the expression levels of OAS gene family network in brain biopsies of macaques with SIVE vs uninfected animals, as well as post-mortem brain of individuals with HAND (on or off ART) vs uninfected controls and three brain regions of HIV-infected individuals with both neurocognitive impairment (HAD) and encephalitis (HIVE). All OAS genes were upregulated both in SIVE and in HAND. OAS expression was significantly higher in high-viremic individuals; increased expression levels persisted in cART subjects when compared to healthy controls. OAS gene network analysis showed that several genes belonging to the type I IFN pathway, especially
CXCL10
and
IFIT3
, were similarly upregulated in SIVE/HAND. Furthermore, we identified a significant upregulation of OAS gene family RNA expression in basal ganglia, white matter, and frontal cortex of HIV-1, HAD, and HAD/HIVE patients compared to healthy subjects. OAS gene family expression is increased in brain sections from individuals with HAND, HAD, and HIVE as well as macaques with SIVE. OAS family expression is likely to be induced by IFN as a consequence of viral replication in the CNS. Its long-term upregulation may contribute to the chronic inflammatory status and neurocognitive impairment we still observe in virologically suppressed individuals on c-ART. |
| doi_str_mv | 10.1007/s12035-017-0460-3 |
| format | Article |
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CXCL10
and
IFIT3
, were similarly upregulated in SIVE/HAND. Furthermore, we identified a significant upregulation of OAS gene family RNA expression in basal ganglia, white matter, and frontal cortex of HIV-1, HAD, and HAD/HIVE patients compared to healthy subjects. OAS gene family expression is increased in brain sections from individuals with HAND, HAD, and HIVE as well as macaques with SIVE. OAS family expression is likely to be induced by IFN as a consequence of viral replication in the CNS. Its long-term upregulation may contribute to the chronic inflammatory status and neurocognitive impairment we still observe in virologically suppressed individuals on c-ART.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-017-0460-3</identifier><identifier>PMID: 28236279</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>2',5'-Oligoadenylate Synthetase - biosynthesis ; 2',5'-Oligoadenylate Synthetase - genetics ; Animals ; Antiretroviral agents ; Antiretroviral drugs ; Antiretroviral therapy ; Basal ganglia ; Biomedical and Life Sciences ; Biomedicine ; Brain ; Cell activation ; Cell Biology ; Central nervous system ; Cognition ; Cortex (frontal) ; CXCL10 protein ; Databases, Genetic ; Dementia disorders ; DNA microarrays ; Encephalitis ; Gene Expression ; Gene Regulatory Networks - genetics ; Genes ; Genetic Association Studies - methods ; Hippocampus - metabolism ; HIV ; HIV Infections - complications ; HIV Infections - genetics ; HIV Infections - metabolism ; Human immunodeficiency virus ; Humans ; Immune response ; Inflammation ; Interferon ; Macaca mulatta ; Male ; Monocytes ; Neurobiology ; Neurocognitive Disorders - etiology ; Neurocognitive Disorders - genetics ; Neurocognitive Disorders - metabolism ; Neurology ; Neurosciences ; Ribonuclease L ; Ribonucleic acid ; RNA ; Simian Acquired Immunodeficiency Syndrome - complications ; Simian Acquired Immunodeficiency Syndrome - genetics ; Simian Acquired Immunodeficiency Syndrome - metabolism ; Substantia alba</subject><ispartof>Molecular neurobiology, 2018-03, Vol.55 (3), p.1905-1914</ispartof><rights>Springer Science+Business Media New York 2017</rights><rights>Molecular Neurobiology is a copyright of Springer, (2017). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-fb37440e3575554c2a903f9ae4acedbb7acd7435d5f889be219529bbf2686fbd3</citedby><cites>FETCH-LOGICAL-c372t-fb37440e3575554c2a903f9ae4acedbb7acd7435d5f889be219529bbf2686fbd3</cites><orcidid>0000-0002-1837-9325</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-017-0460-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-017-0460-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28236279$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sanfilippo, C.</creatorcontrib><creatorcontrib>Pinzone, M.R.</creatorcontrib><creatorcontrib>Cambria, D.</creatorcontrib><creatorcontrib>Longo, A.</creatorcontrib><creatorcontrib>Palumbo, M.</creatorcontrib><creatorcontrib>Di Marco, R.</creatorcontrib><creatorcontrib>Condorelli, F.</creatorcontrib><creatorcontrib>Nunnari, G.</creatorcontrib><creatorcontrib>Malaguarnera, L.</creatorcontrib><creatorcontrib>Di Rosa, M.</creatorcontrib><title>OAS Gene Family Expression Is Associated with HIV-Related Neurocognitive Disorders</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>HIV-associated neurocognitive disorders are common in HIV-infected individuals, even in the combination antiretroviral therapy (c-ART) era. Several mechanisms are involved in neuronal damage, including chronic inflammation immune activation. Mammalian 2′-5′-oligoadenylate synthetase (OAS) genes are produced in response to interferon (IFN), mainly by monocytes, and exert their antiviral functions by activation of RNase L that degrades viral and cellular RNAs. In this study, we aimed at exploring OAS gene family RNA expression in simian immunodeficiency virus encephalitis (SIVE), in HIV-associated neurocognitive disorders (HAND), and in HIV-associate dementia (HAD). We analyzed three microarray datasets obtained from the NCBI in order to assess the expression levels of OAS gene family network in brain biopsies of macaques with SIVE vs uninfected animals, as well as post-mortem brain of individuals with HAND (on or off ART) vs uninfected controls and three brain regions of HIV-infected individuals with both neurocognitive impairment (HAD) and encephalitis (HIVE). All OAS genes were upregulated both in SIVE and in HAND. OAS expression was significantly higher in high-viremic individuals; increased expression levels persisted in cART subjects when compared to healthy controls. OAS gene network analysis showed that several genes belonging to the type I IFN pathway, especially
CXCL10
and
IFIT3
, were similarly upregulated in SIVE/HAND. Furthermore, we identified a significant upregulation of OAS gene family RNA expression in basal ganglia, white matter, and frontal cortex of HIV-1, HAD, and HAD/HIVE patients compared to healthy subjects. OAS gene family expression is increased in brain sections from individuals with HAND, HAD, and HIVE as well as macaques with SIVE. OAS family expression is likely to be induced by IFN as a consequence of viral replication in the CNS. Its long-term upregulation may contribute to the chronic inflammatory status and neurocognitive impairment we still observe in virologically suppressed individuals on c-ART.</description><subject>2',5'-Oligoadenylate Synthetase - biosynthesis</subject><subject>2',5'-Oligoadenylate Synthetase - genetics</subject><subject>Animals</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Antiretroviral therapy</subject><subject>Basal ganglia</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Cell activation</subject><subject>Cell Biology</subject><subject>Central nervous system</subject><subject>Cognition</subject><subject>Cortex (frontal)</subject><subject>CXCL10 protein</subject><subject>Databases, Genetic</subject><subject>Dementia disorders</subject><subject>DNA microarrays</subject><subject>Encephalitis</subject><subject>Gene Expression</subject><subject>Gene Regulatory Networks - genetics</subject><subject>Genes</subject><subject>Genetic Association Studies - methods</subject><subject>Hippocampus - metabolism</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - genetics</subject><subject>HIV Infections - metabolism</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immune response</subject><subject>Inflammation</subject><subject>Interferon</subject><subject>Macaca mulatta</subject><subject>Male</subject><subject>Monocytes</subject><subject>Neurobiology</subject><subject>Neurocognitive Disorders - etiology</subject><subject>Neurocognitive Disorders - genetics</subject><subject>Neurocognitive Disorders - metabolism</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Ribonuclease L</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Simian Acquired Immunodeficiency Syndrome - complications</subject><subject>Simian Acquired Immunodeficiency Syndrome - 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biosynthesis</topic><topic>2',5'-Oligoadenylate Synthetase - genetics</topic><topic>Animals</topic><topic>Antiretroviral agents</topic><topic>Antiretroviral drugs</topic><topic>Antiretroviral therapy</topic><topic>Basal ganglia</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Cell activation</topic><topic>Cell Biology</topic><topic>Central nervous system</topic><topic>Cognition</topic><topic>Cortex (frontal)</topic><topic>CXCL10 protein</topic><topic>Databases, Genetic</topic><topic>Dementia disorders</topic><topic>DNA microarrays</topic><topic>Encephalitis</topic><topic>Gene Expression</topic><topic>Gene Regulatory Networks - genetics</topic><topic>Genes</topic><topic>Genetic Association Studies - methods</topic><topic>Hippocampus - metabolism</topic><topic>HIV</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - genetics</topic><topic>HIV Infections - metabolism</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immune response</topic><topic>Inflammation</topic><topic>Interferon</topic><topic>Macaca mulatta</topic><topic>Male</topic><topic>Monocytes</topic><topic>Neurobiology</topic><topic>Neurocognitive Disorders - etiology</topic><topic>Neurocognitive Disorders - genetics</topic><topic>Neurocognitive Disorders - metabolism</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Ribonuclease L</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Simian Acquired Immunodeficiency Syndrome - complications</topic><topic>Simian Acquired Immunodeficiency Syndrome - genetics</topic><topic>Simian Acquired Immunodeficiency Syndrome - metabolism</topic><topic>Substantia alba</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sanfilippo, C.</creatorcontrib><creatorcontrib>Pinzone, M.R.</creatorcontrib><creatorcontrib>Cambria, D.</creatorcontrib><creatorcontrib>Longo, A.</creatorcontrib><creatorcontrib>Palumbo, M.</creatorcontrib><creatorcontrib>Di Marco, R.</creatorcontrib><creatorcontrib>Condorelli, F.</creatorcontrib><creatorcontrib>Nunnari, G.</creatorcontrib><creatorcontrib>Malaguarnera, L.</creatorcontrib><creatorcontrib>Di Rosa, M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>ProQuest Science Journals</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sanfilippo, C.</au><au>Pinzone, M.R.</au><au>Cambria, D.</au><au>Longo, A.</au><au>Palumbo, M.</au><au>Di Marco, R.</au><au>Condorelli, F.</au><au>Nunnari, G.</au><au>Malaguarnera, L.</au><au>Di Rosa, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>OAS Gene Family Expression Is Associated with HIV-Related Neurocognitive Disorders</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2018-03-01</date><risdate>2018</risdate><volume>55</volume><issue>3</issue><spage>1905</spage><epage>1914</epage><pages>1905-1914</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>HIV-associated neurocognitive disorders are common in HIV-infected individuals, even in the combination antiretroviral therapy (c-ART) era. Several mechanisms are involved in neuronal damage, including chronic inflammation immune activation. Mammalian 2′-5′-oligoadenylate synthetase (OAS) genes are produced in response to interferon (IFN), mainly by monocytes, and exert their antiviral functions by activation of RNase L that degrades viral and cellular RNAs. In this study, we aimed at exploring OAS gene family RNA expression in simian immunodeficiency virus encephalitis (SIVE), in HIV-associated neurocognitive disorders (HAND), and in HIV-associate dementia (HAD). We analyzed three microarray datasets obtained from the NCBI in order to assess the expression levels of OAS gene family network in brain biopsies of macaques with SIVE vs uninfected animals, as well as post-mortem brain of individuals with HAND (on or off ART) vs uninfected controls and three brain regions of HIV-infected individuals with both neurocognitive impairment (HAD) and encephalitis (HIVE). All OAS genes were upregulated both in SIVE and in HAND. OAS expression was significantly higher in high-viremic individuals; increased expression levels persisted in cART subjects when compared to healthy controls. OAS gene network analysis showed that several genes belonging to the type I IFN pathway, especially
CXCL10
and
IFIT3
, were similarly upregulated in SIVE/HAND. Furthermore, we identified a significant upregulation of OAS gene family RNA expression in basal ganglia, white matter, and frontal cortex of HIV-1, HAD, and HAD/HIVE patients compared to healthy subjects. OAS gene family expression is increased in brain sections from individuals with HAND, HAD, and HIVE as well as macaques with SIVE. OAS family expression is likely to be induced by IFN as a consequence of viral replication in the CNS. Its long-term upregulation may contribute to the chronic inflammatory status and neurocognitive impairment we still observe in virologically suppressed individuals on c-ART.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28236279</pmid><doi>10.1007/s12035-017-0460-3</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-1837-9325</orcidid></addata></record> |
| fulltext | fulltext |
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| ispartof | Molecular neurobiology, 2018-03, Vol.55 (3), p.1905-1914 |
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| subjects | 2',5'-Oligoadenylate Synthetase - biosynthesis 2',5'-Oligoadenylate Synthetase - genetics Animals Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Basal ganglia Biomedical and Life Sciences Biomedicine Brain Cell activation Cell Biology Central nervous system Cognition Cortex (frontal) CXCL10 protein Databases, Genetic Dementia disorders DNA microarrays Encephalitis Gene Expression Gene Regulatory Networks - genetics Genes Genetic Association Studies - methods Hippocampus - metabolism HIV HIV Infections - complications HIV Infections - genetics HIV Infections - metabolism Human immunodeficiency virus Humans Immune response Inflammation Interferon Macaca mulatta Male Monocytes Neurobiology Neurocognitive Disorders - etiology Neurocognitive Disorders - genetics Neurocognitive Disorders - metabolism Neurology Neurosciences Ribonuclease L Ribonucleic acid RNA Simian Acquired Immunodeficiency Syndrome - complications Simian Acquired Immunodeficiency Syndrome - genetics Simian Acquired Immunodeficiency Syndrome - metabolism Substantia alba |
| title | OAS Gene Family Expression Is Associated with HIV-Related Neurocognitive Disorders |
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