The far-reaching HAND of cART: cART effects on astrocytes
Following the introduction of combination antiretroviral therapy (cART), the morbidity and mortality from human immunodeficiency virus (HIV) infection has been drastically curtailed and HIV has now become a chronic manageable disease. Persons living with HIV (PLWH) are living longer and experiencing...
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| Veröffentlicht in: | Journal of neuroimmune pharmacology 2021-03, Vol.16 (1), p.144-158 |
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| creator | Gonzalez, Hemil Podany, Anthony Al-Harthi, Lena Wallace, Jennillee |
| description | Following the introduction of combination antiretroviral therapy (cART), the morbidity and mortality from human immunodeficiency virus (HIV) infection has been drastically curtailed and HIV has now become a chronic manageable disease. Persons living with HIV (PLWH) are living longer and experiencing significant co-morbidities and conditions of aging. NeuroHIV, clinically defined as HIV-Associated Neurocognitive Disorders (HAND) and pathologically manifested by persistent inflammation in the CNS despite cART, is a significant co-morbid condition for PLWH. In the pre-cART era, HIV mediated much of the pathogenesis in the Central Nervous System (CNS); in the cART era, with low to undetectable viremia, other mechanisms may be contributing to persistent neuroinflammation. Emerging data point to the adverse effects at the cellular level of cART, independent of HIV. Astrocytes are the most abundant cells in the CNS, playing vital roles in maintaining CNS homeostasis (e.g. metabolic support to neurons, clearance of neurotransmitters, ion balance, modulation of synaptic functions and maintaining the structural integrity of the blood brain barrier (BBB). Therefore, any disruption of their function will have wide repercussions in the CNS. In this review, we will address current knowledge and gaps on the impact of antiretrovirals (ARVs) on astrocytes and physiologic consequences in the CNS. Understanding the status of this field, will provide a practical framework to elucidate the potential role of cART-mediated dysregulation of astrocytes in neuroHIV pathogenesis and inform therapeutic strategies that are “neuro-friendly”.
Graphical abstract
CNS-penetrating cART have the potential to cause resting astrocytes to become activated into an A1 or neurotoxic phenotype. These cells can in turn secrete inflammatory cytokines that affect surrounding microglia macrophages, as well as neurotoxic factors that impact nearby neurons. In addition, impairment in the physiologic functions of astrocytes will result in altered BBB permeability and disrupted metabolic homeostasis. CNS=Central Nervous System; cART=combined antiretroviral therapy; BBB=blood brain barrier |
| doi_str_mv | 10.1007/s11481-020-09907-w |
| format | Article |
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Graphical abstract
CNS-penetrating cART have the potential to cause resting astrocytes to become activated into an A1 or neurotoxic phenotype. These cells can in turn secrete inflammatory cytokines that affect surrounding microglia macrophages, as well as neurotoxic factors that impact nearby neurons. In addition, impairment in the physiologic functions of astrocytes will result in altered BBB permeability and disrupted metabolic homeostasis. CNS=Central Nervous System; cART=combined antiretroviral therapy; BBB=blood brain barrier</description><identifier>ISSN: 1557-1890</identifier><identifier>EISSN: 1557-1904</identifier><identifier>DOI: 10.1007/s11481-020-09907-w</identifier><identifier>PMID: 32147775</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Aging - drug effects ; AIDS Dementia Complex - drug therapy ; AIDS Dementia Complex - epidemiology ; Animals ; Anti-HIV Agents - adverse effects ; Anti-HIV Agents - pharmacology ; Anti-HIV Agents - therapeutic use ; Antiretroviral Therapy, Highly Active ; Astrocytes - drug effects ; Biomedical and Life Sciences ; Biomedicine ; Calcium - metabolism ; Cell Biology ; Cellular Senescence - drug effects ; Central Nervous System - drug effects ; Glucose - metabolism ; Glutamic Acid - metabolism ; Glutamine - metabolism ; HIV ; HIV Infections - complications ; HIV Infections - drug therapy ; HIV-1 - physiology ; Human immunodeficiency virus ; Humans ; Immunology ; Invited Review ; Mitochondria - drug effects ; Mitochondria - physiology ; Neurocognitive Disorders - chemically induced ; Neurosciences ; Oxidative Stress ; Pathogenesis ; Pharmacology/Toxicology ; Phenotype ; Prevalence ; Rats ; Virology</subject><ispartof>Journal of neuroimmune pharmacology, 2021-03, Vol.16 (1), p.144-158</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-5497e376954bb2ad77b169494137762ec415ba6e88bf29229da4e8844036d2b83</citedby><cites>FETCH-LOGICAL-c474t-5497e376954bb2ad77b169494137762ec415ba6e88bf29229da4e8844036d2b83</cites><orcidid>0000-0003-3517-1398</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/s11481-020-09907-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11481-020-09907-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32147775$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gonzalez, Hemil</creatorcontrib><creatorcontrib>Podany, Anthony</creatorcontrib><creatorcontrib>Al-Harthi, Lena</creatorcontrib><creatorcontrib>Wallace, Jennillee</creatorcontrib><title>The far-reaching HAND of cART: cART effects on astrocytes</title><title>Journal of neuroimmune pharmacology</title><addtitle>J Neuroimmune Pharmacol</addtitle><addtitle>J Neuroimmune Pharmacol</addtitle><description>Following the introduction of combination antiretroviral therapy (cART), the morbidity and mortality from human immunodeficiency virus (HIV) infection has been drastically curtailed and HIV has now become a chronic manageable disease. Persons living with HIV (PLWH) are living longer and experiencing significant co-morbidities and conditions of aging. NeuroHIV, clinically defined as HIV-Associated Neurocognitive Disorders (HAND) and pathologically manifested by persistent inflammation in the CNS despite cART, is a significant co-morbid condition for PLWH. In the pre-cART era, HIV mediated much of the pathogenesis in the Central Nervous System (CNS); in the cART era, with low to undetectable viremia, other mechanisms may be contributing to persistent neuroinflammation. Emerging data point to the adverse effects at the cellular level of cART, independent of HIV. Astrocytes are the most abundant cells in the CNS, playing vital roles in maintaining CNS homeostasis (e.g. metabolic support to neurons, clearance of neurotransmitters, ion balance, modulation of synaptic functions and maintaining the structural integrity of the blood brain barrier (BBB). Therefore, any disruption of their function will have wide repercussions in the CNS. In this review, we will address current knowledge and gaps on the impact of antiretrovirals (ARVs) on astrocytes and physiologic consequences in the CNS. Understanding the status of this field, will provide a practical framework to elucidate the potential role of cART-mediated dysregulation of astrocytes in neuroHIV pathogenesis and inform therapeutic strategies that are “neuro-friendly”.
Graphical abstract
CNS-penetrating cART have the potential to cause resting astrocytes to become activated into an A1 or neurotoxic phenotype. These cells can in turn secrete inflammatory cytokines that affect surrounding microglia macrophages, as well as neurotoxic factors that impact nearby neurons. In addition, impairment in the physiologic functions of astrocytes will result in altered BBB permeability and disrupted metabolic homeostasis. CNS=Central Nervous System; cART=combined antiretroviral therapy; BBB=blood brain barrier</description><subject>Aging - drug effects</subject><subject>AIDS Dementia Complex - drug therapy</subject><subject>AIDS Dementia Complex - epidemiology</subject><subject>Animals</subject><subject>Anti-HIV Agents - adverse effects</subject><subject>Anti-HIV Agents - pharmacology</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretroviral Therapy, Highly Active</subject><subject>Astrocytes - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Calcium - metabolism</subject><subject>Cell Biology</subject><subject>Cellular Senescence - drug effects</subject><subject>Central Nervous System - drug effects</subject><subject>Glucose - metabolism</subject><subject>Glutamic Acid - metabolism</subject><subject>Glutamine - metabolism</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - drug therapy</subject><subject>HIV-1 - physiology</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunology</subject><subject>Invited Review</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - physiology</subject><subject>Neurocognitive Disorders - chemically induced</subject><subject>Neurosciences</subject><subject>Oxidative Stress</subject><subject>Pathogenesis</subject><subject>Pharmacology/Toxicology</subject><subject>Phenotype</subject><subject>Prevalence</subject><subject>Rats</subject><subject>Virology</subject><issn>1557-1890</issn><issn>1557-1904</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kE9LAzEQxYMoVqtfwIMseI5Ostlk40Eo9U-FoiD1HLK72XZLu6nJ1tJvb-y2VS9eJhPmzZvHD6ELAtcEQNx4QlhKMFDAICUIvDpAJyRJBCYS2OGuTyV00Kn3UwDGGMAx6sSUMCFEcoLkaGKiUjvsjM4nVT2OBr2X-8iWUd57G91uamTK0uSNj2wdad84m68b48_QUaln3pxv3y56f3wY9Qd4-Pr03O8Ncc4Ea3DCpDCx4DJhWUZ1IURGuGSSkVgITk3OSJJpbtI0K6mkVBaahU8IGvOCZmncRXet72KZzU2Rm7pxeqYWrpprt1ZWV-rvpK4mamw_lWBpLFIWDK62Bs5-LI1v1NQuXR0yK5oAEE45h6CirSp31ntnyv0FAuobt2pxq4BbbXCrVVi6_J1tv7LjGwRxK_BhVI-N-7n9j-0X_sqJDQ</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Gonzalez, Hemil</creator><creator>Podany, Anthony</creator><creator>Al-Harthi, Lena</creator><creator>Wallace, Jennillee</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3517-1398</orcidid></search><sort><creationdate>20210301</creationdate><title>The far-reaching HAND of cART: cART effects on astrocytes</title><author>Gonzalez, Hemil ; 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Persons living with HIV (PLWH) are living longer and experiencing significant co-morbidities and conditions of aging. NeuroHIV, clinically defined as HIV-Associated Neurocognitive Disorders (HAND) and pathologically manifested by persistent inflammation in the CNS despite cART, is a significant co-morbid condition for PLWH. In the pre-cART era, HIV mediated much of the pathogenesis in the Central Nervous System (CNS); in the cART era, with low to undetectable viremia, other mechanisms may be contributing to persistent neuroinflammation. Emerging data point to the adverse effects at the cellular level of cART, independent of HIV. Astrocytes are the most abundant cells in the CNS, playing vital roles in maintaining CNS homeostasis (e.g. metabolic support to neurons, clearance of neurotransmitters, ion balance, modulation of synaptic functions and maintaining the structural integrity of the blood brain barrier (BBB). Therefore, any disruption of their function will have wide repercussions in the CNS. In this review, we will address current knowledge and gaps on the impact of antiretrovirals (ARVs) on astrocytes and physiologic consequences in the CNS. Understanding the status of this field, will provide a practical framework to elucidate the potential role of cART-mediated dysregulation of astrocytes in neuroHIV pathogenesis and inform therapeutic strategies that are “neuro-friendly”.
Graphical abstract
CNS-penetrating cART have the potential to cause resting astrocytes to become activated into an A1 or neurotoxic phenotype. These cells can in turn secrete inflammatory cytokines that affect surrounding microglia macrophages, as well as neurotoxic factors that impact nearby neurons. In addition, impairment in the physiologic functions of astrocytes will result in altered BBB permeability and disrupted metabolic homeostasis. CNS=Central Nervous System; cART=combined antiretroviral therapy; BBB=blood brain barrier</abstract><cop>New York</cop><pub>Springer US</pub><pmid>32147775</pmid><doi>10.1007/s11481-020-09907-w</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-3517-1398</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aging - drug effects AIDS Dementia Complex - drug therapy AIDS Dementia Complex - epidemiology Animals Anti-HIV Agents - adverse effects Anti-HIV Agents - pharmacology Anti-HIV Agents - therapeutic use Antiretroviral Therapy, Highly Active Astrocytes - drug effects Biomedical and Life Sciences Biomedicine Calcium - metabolism Cell Biology Cellular Senescence - drug effects Central Nervous System - drug effects Glucose - metabolism Glutamic Acid - metabolism Glutamine - metabolism HIV HIV Infections - complications HIV Infections - drug therapy HIV-1 - physiology Human immunodeficiency virus Humans Immunology Invited Review Mitochondria - drug effects Mitochondria - physiology Neurocognitive Disorders - chemically induced Neurosciences Oxidative Stress Pathogenesis Pharmacology/Toxicology Phenotype Prevalence Rats Virology |
| title | The far-reaching HAND of cART: cART effects on astrocytes |
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