Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction
Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma...
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| Published in | Journal of virology Vol. 97; no. 2; p. e0165522 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Society for Microbiology
28.02.2023
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control.
The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (
n
= 9) or delayed initiation (
n
= 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in
in vitro
systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure.
IMPORTANCE
Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD
+
deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection.
In vitro
infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction. |
|---|---|
| AbstractList | The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD+ deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction.The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD+ deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction. The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate ( = 9) or delayed initiation ( = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction. The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate ( n = 9) or delayed initiation ( n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD + deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction. The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD+ deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction. Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate ( n = 9) or delayed initiation ( n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD + deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction. Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure.IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD(+) deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction. |
| Author | Martinez-Picado, Javier Wyss-Coray, Tony Gisslén, Magnus Ballana, Esther Silva-Arrieta, Sandra Kobayashi-Ishihara, Mie Hartigan-O’Connor, Dennis Prado, Julia G. Clotet, Bonaventura Brander, Christian Ruiz-Riol, Marta Sanchez, Jorge Llano, Anuska Kawana-Tachikawa, Ai Peña, Ruth Mothe, Beatriz Oriol-Tordera, Bruna Riveira-Muñoz, Eva Price, Richard W. Soriano-Mas, Carles Prats, Anna Duran-Castells, Clara Muñoz-Moreno, José Antonio Gálvez, Cristina Meyerhans, Andreas Martinez-Zalacain, Ignacio |
| Author_xml | – sequence: 1 givenname: Clara surname: Duran-Castells fullname: Duran-Castells, Clara organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain, Departament de Biologia, Cel·lular, Fisiologia i d’immunologia, Facultat de Medicina, Universitat Autonoma de Barcelona, Cerdanyola del Valles, Spain – sequence: 2 givenname: Anuska surname: Llano fullname: Llano, Anuska organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain – sequence: 3 givenname: Ai orcidid: 0000-0002-3082-5324 surname: Kawana-Tachikawa fullname: Kawana-Tachikawa, Ai organization: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan – sequence: 4 givenname: Anna surname: Prats fullname: Prats, Anna organization: Fundació Lluita contra la Sida and Infectious Diseases Department, Hospital Germans Trias i Pujol, Badalona, Spain – sequence: 5 givenname: Ignacio surname: Martinez-Zalacain fullname: Martinez-Zalacain, Ignacio organization: Department of Psychiatry, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain – sequence: 6 givenname: Mie surname: Kobayashi-Ishihara fullname: Kobayashi-Ishihara, Mie organization: Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, Spain – sequence: 7 givenname: Bruna surname: Oriol-Tordera fullname: Oriol-Tordera, Bruna organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain, Departament de Biologia, Cel·lular, Fisiologia i d’immunologia, Facultat de Medicina, Universitat Autonoma de Barcelona, Cerdanyola del Valles, Spain – sequence: 8 givenname: Ruth surname: Peña fullname: Peña, Ruth organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain – sequence: 9 givenname: Cristina surname: Gálvez fullname: Gálvez, Cristina organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain – sequence: 10 givenname: Sandra surname: Silva-Arrieta fullname: Silva-Arrieta, Sandra organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain – sequence: 11 givenname: Bonaventura surname: Clotet fullname: Clotet, Bonaventura organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain, Fundació Lluita contra la Sida and Infectious Diseases Department, Hospital Germans Trias i Pujol, Badalona, Spain, Universitat de Vic - Universitat Central de Catalunya (UVic-UCC), Vic, Spain – sequence: 12 givenname: Eva surname: Riveira-Muñoz fullname: Riveira-Muñoz, Eva organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain – sequence: 13 givenname: Esther orcidid: 0000-0002-5215-7363 surname: Ballana fullname: Ballana, Esther organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain – sequence: 14 givenname: Julia G. surname: Prado fullname: Prado, Julia G. organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain, Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain, CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain – sequence: 15 givenname: Javier orcidid: 0000-0002-4916-2129 surname: Martinez-Picado fullname: Martinez-Picado, Javier organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain, Universitat de Vic - Universitat Central de Catalunya (UVic-UCC), Vic, Spain, ICREA, Barcelona, Spain, CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain – sequence: 16 givenname: Jorge surname: Sanchez fullname: Sanchez, Jorge organization: Centro de Investigaciones Tecnologicas Biomedicas y Medioambientales, CITBM, Lima, Peru – sequence: 17 givenname: Beatriz orcidid: 0000-0001-9975-407X surname: Mothe fullname: Mothe, Beatriz organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain, Fundació Lluita contra la Sida and Infectious Diseases Department, Hospital Germans Trias i Pujol, Badalona, Spain, Universitat de Vic - Universitat Central de Catalunya (UVic-UCC), Vic, Spain, CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain – sequence: 18 givenname: Dennis surname: Hartigan-O’Connor fullname: Hartigan-O’Connor, Dennis organization: Department of Medical Microbiology and Immunology, University of California, Davis, California, USA – sequence: 19 givenname: Tony surname: Wyss-Coray fullname: Wyss-Coray, Tony organization: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA – sequence: 20 givenname: Andreas surname: Meyerhans fullname: Meyerhans, Andreas organization: Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra, Barcelona, Spain, ICREA, Barcelona, Spain – sequence: 21 givenname: Magnus surname: Gisslén fullname: Gisslén, Magnus organization: Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden – sequence: 22 givenname: Richard W. surname: Price fullname: Price, Richard W. organization: Department of Neurology, University of California San Francisco, San Francisco, California, USA – sequence: 23 givenname: Carles surname: Soriano-Mas fullname: Soriano-Mas, Carles organization: Department of Psychiatry, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain, Department of Clinical Sciences, University of Barcelona, Barcelona, Spain, Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain – sequence: 24 givenname: José Antonio surname: Muñoz-Moreno fullname: Muñoz-Moreno, José Antonio organization: Fundació Lluita contra la Sida and Infectious Diseases Department, Hospital Germans Trias i Pujol, Badalona, Spain, Faculty of Psychology and Education Sciences, Universitat Oberta de Catalunya (UOC), Barcelona, Spain – sequence: 25 givenname: Christian surname: Brander fullname: Brander, Christian organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain, Universitat de Vic - Universitat Central de Catalunya (UVic-UCC), Vic, Spain, ICREA, Barcelona, Spain, CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain – sequence: 26 givenname: Marta orcidid: 0000-0003-1899-8879 surname: Ruiz-Riol fullname: Ruiz-Riol, Marta organization: IrsiCaixa AIDS Research Institute, Hospital Germans Trias i Pujol, Badalona, Spain, CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36719240$$D View this record in MEDLINE/PubMed https://gup.ub.gu.se/publication/324546$$DView record from Swedish Publication Index |
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| CitedBy_id | crossref_primary_10_12677_jcpm_2024_34257 crossref_primary_10_3390_molecules28227655 crossref_primary_10_1016_j_plrev_2025_03_020 crossref_primary_10_3389_fnmol_2024_1394886 crossref_primary_10_3390_ph17101298 crossref_primary_10_1128_msystems_00510_23 crossref_primary_10_4103_NRR_NRR_D_23_02063 |
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| ContentType | Journal Article |
| Copyright | Copyright © 2023 Duran-Castells et al. Copyright © 2023 Duran-Castells et al. 2023 Duran-Castells et al. |
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| DOI | 10.1128/jvi.01655-22 |
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| Keywords | HIV-1 plasma proteomics HIV-associated neurocognitive disorders (HAND) virus infection control HIV reservoir neuroimaging neurological disorder |
| Language | English |
| License | This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. https://creativecommons.org/licenses/by/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Christian Brander and Marta Ruiz-Riol contributed equally to this work. The authors declare no conflict of interest. |
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| Snippet | Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To... The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH).... |
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| SubjectTerms | Biomarkers Clinical Medicine disorders (HAND) Genomics and Proteomics HIV Infections - complications HIV Infections - drug therapy HIV reservoir HIV-1 HIV-associated neurocognitive Humans Klinisk medicin Nervous System Diseases - drug therapy Nervous System Diseases - etiology Nervous System Diseases - virology Neurofilament Proteins - metabolism neuroimaging neurological disorder plasma proteomics Proviruses - metabolism Quality of Life Sirtuin 2 - metabolism Viral Load virus infection control Virus-Cell Interactions |
| Title | Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction |
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