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Mice Chronically Infected with Chimeric HIV Resist Peripheral and Brain Superinfection: A Model of Protective Immunity to HIV

Identifieur interne : 001098 ( Istex/Corpus ); précédent : 001097; suivant : 001099

Mice Chronically Infected with Chimeric HIV Resist Peripheral and Brain Superinfection: A Model of Protective Immunity to HIV

Auteurs : Jennifer L. Kelschenbach ; Manisha Saini ; Eran Hadas ; Chao-Jiang Gu ; Wei Chao ; Galina Bentsman ; Jessie P. Hong ; Tomas Hanke ; Leroy R. Sharer ; Mary Jane Potash ; David J. Volsky

Source :

RBID : ISTEX:4965E275D19BC1D93D36047D12435B604366B022

English descriptors

Abstract

Abstract: Infection by some viruses induces immunity to reinfection, providing a means to identify protective epitopes. To investigate resistance to reinfection in an animal model of HIV disease and its control, we employed infection of mice with chimeric HIV, EcoHIV. When immunocompetent mice were infected by intraperitoneal (IP) injection of EcoHIV, they resisted subsequent secondary infection by IP injection, consistent with a systemic antiviral immune response. To investigate the potential role of these responses in restricting neurotropic HIV infection, we established a protocol for efficient EcoHIV expression in the brain following intracranial (IC) inoculation of virus. When mice were inoculated by IP injection and secondarily by IC injection, they also controlled EcoHIV replication in the brain. To investigate their role in EcoHIV antiviral responses, CD8+ T lymphocytes were isolated from spleens of EcoHIV infected and uninfected mice and adoptively transferred to isogenic recipients. Recipients of EcoHIV primed CD8+ cells resisted subsequent EcoHIV infection compared to recipients of cells from uninfected donors. CD8+ spleen cells from EcoHIV-infected mice also mounted modest but significant interferon-γ responses to two HIV Gag peptide pools. These findings suggest EcoHIV-infected mice may serve as a useful system to investigate the induction of anti-HIV protective immunity for eventual translation to human beings.

Url:
DOI: 10.1007/s11481-011-9316-1

Links to Exploration step

ISTEX:4965E275D19BC1D93D36047D12435B604366B022

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<div type="abstract" xml:lang="en">Abstract: Infection by some viruses induces immunity to reinfection, providing a means to identify protective epitopes. To investigate resistance to reinfection in an animal model of HIV disease and its control, we employed infection of mice with chimeric HIV, EcoHIV. When immunocompetent mice were infected by intraperitoneal (IP) injection of EcoHIV, they resisted subsequent secondary infection by IP injection, consistent with a systemic antiviral immune response. To investigate the potential role of these responses in restricting neurotropic HIV infection, we established a protocol for efficient EcoHIV expression in the brain following intracranial (IC) inoculation of virus. When mice were inoculated by IP injection and secondarily by IC injection, they also controlled EcoHIV replication in the brain. To investigate their role in EcoHIV antiviral responses, CD8+ T lymphocytes were isolated from spleens of EcoHIV infected and uninfected mice and adoptively transferred to isogenic recipients. Recipients of EcoHIV primed CD8+ cells resisted subsequent EcoHIV infection compared to recipients of cells from uninfected donors. CD8+ spleen cells from EcoHIV-infected mice also mounted modest but significant interferon-γ responses to two HIV Gag peptide pools. These findings suggest EcoHIV-infected mice may serve as a useful system to investigate the induction of anti-HIV protective immunity for eventual translation to human beings.</div>
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<affiliation>Molecular Virology Division, St. Luke’s-Roosevelt Hospital Center, 432 West 58th Street, Antenucci Research Building, Room 709, 10019, New York, NY, USA</affiliation>
<affiliation>E-mail: wei616@verizon.net</affiliation>
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<namePart type="given">Jessie</namePart>
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<namePart type="family">Hong</namePart>
<affiliation>Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, OX3 9DS, Oxford, UK</affiliation>
<affiliation>E-mail: jessie.hong@gmail.com</affiliation>
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<namePart type="given">Tomas</namePart>
<namePart type="family">Hanke</namePart>
<affiliation>Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, OX3 9DS, Oxford, UK</affiliation>
<affiliation>E-mail: tomas.hanke@molecular-medicine.oxford.ac.uk</affiliation>
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<name type="personal">
<namePart type="given">Leroy</namePart>
<namePart type="given">R.</namePart>
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<affiliation>Department of Pathology, New Jersey Medical School, 07103, Newark, NJ, USA</affiliation>
<affiliation>E-mail: sharer@umdnj.edu</affiliation>
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<name type="personal">
<namePart type="given">Mary</namePart>
<namePart type="given">Jane</namePart>
<namePart type="family">Potash</namePart>
<affiliation>Molecular Virology Division, St. Luke’s-Roosevelt Hospital Center, 432 West 58th Street, Antenucci Research Building, Room 709, 10019, New York, NY, USA</affiliation>
<affiliation>Department of Pathology & Cell Biology, Columbia University, 10032, New York, NY, USA</affiliation>
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<namePart type="given">David</namePart>
<namePart type="given">J.</namePart>
<namePart type="family">Volsky</namePart>
<affiliation>Molecular Virology Division, St. Luke’s-Roosevelt Hospital Center, 432 West 58th Street, Antenucci Research Building, Room 709, 10019, New York, NY, USA</affiliation>
<affiliation>Department of Pathology & Cell Biology, Columbia University, 10032, New York, NY, USA</affiliation>
<affiliation>E-mail: djv4@columbia.edu</affiliation>
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<abstract lang="en">Abstract: Infection by some viruses induces immunity to reinfection, providing a means to identify protective epitopes. To investigate resistance to reinfection in an animal model of HIV disease and its control, we employed infection of mice with chimeric HIV, EcoHIV. When immunocompetent mice were infected by intraperitoneal (IP) injection of EcoHIV, they resisted subsequent secondary infection by IP injection, consistent with a systemic antiviral immune response. To investigate the potential role of these responses in restricting neurotropic HIV infection, we established a protocol for efficient EcoHIV expression in the brain following intracranial (IC) inoculation of virus. When mice were inoculated by IP injection and secondarily by IC injection, they also controlled EcoHIV replication in the brain. To investigate their role in EcoHIV antiviral responses, CD8+ T lymphocytes were isolated from spleens of EcoHIV infected and uninfected mice and adoptively transferred to isogenic recipients. Recipients of EcoHIV primed CD8+ cells resisted subsequent EcoHIV infection compared to recipients of cells from uninfected donors. CD8+ spleen cells from EcoHIV-infected mice also mounted modest but significant interferon-γ responses to two HIV Gag peptide pools. These findings suggest EcoHIV-infected mice may serve as a useful system to investigate the induction of anti-HIV protective immunity for eventual translation to human beings.</abstract>
<note>ORIGINAL ARTICLE</note>
<subject lang="en">
<genre>Keywords</genre>
<topic>Mouse model</topic>
<topic>Chimeric HIV</topic>
<topic>Superinfection</topic>
<topic>Adaptive immune responses</topic>
<topic>HIV neuropathogenesis</topic>
<topic>Brain</topic>
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<title>Journal of Neuroimmune Pharmacology</title>
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<title>J Neuroimmune Pharmacol</title>
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<namePart type="given">Howard</namePart>
<namePart type="family">Fox</namePart>
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<name type="personal">
<namePart type="given">Howard E.</namePart>
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<dateIssued encoding="w3cdtf">2012-05-16</dateIssued>
<copyrightDate encoding="w3cdtf">2012</copyrightDate>
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<genre>Biomedicine</genre>
<topic>Virology</topic>
<topic>Pharmacology/Toxicology</topic>
<topic>Cell Biology</topic>
<topic>Immunology</topic>
<topic>Neurosciences</topic>
</subject>
<identifier type="ISSN">1557-1890</identifier>
<identifier type="eISSN">1557-1904</identifier>
<identifier type="JournalID">11481</identifier>
<identifier type="IssueArticleCount">19</identifier>
<identifier type="VolumeIssueCount">4</identifier>
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<date>2012</date>
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<title>Special Issue on Animal Models of NeuroAIDS</title>
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<detail type="volume">
<number>7</number>
<caption>vol.</caption>
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<detail type="issue">
<number>2</number>
<caption>no.</caption>
</detail>
<extent unit="pages">
<start>380</start>
<end>387</end>
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<identifier type="DOI">10.1007/s11481-011-9316-1</identifier>
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<accessCondition type="use and reproduction" contentType="copyright">Springer Science+Business Media, LLC, 2011</accessCondition>
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