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

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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.

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Acknowledgments

The authors would like to thank Ms. Ilene M. Totillo for manuscript preparation.

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Authors and Affiliations

  1. Molecular Virology Division, St. Luke’s-Roosevelt Hospital Center, 432 West 58th Street, Antenucci Research Building, Room 709, New York, NY, 10019, USA

    Jennifer L. Kelschenbach, Manisha Saini, Eran Hadas, Chao-jiang Gu, Wei Chao, Galina Bentsman, Mary Jane Potash & David J. Volsky

  2. Department of Pathology & Cell Biology, Columbia University, New York, NY, 10032, USA

    Jennifer L. Kelschenbach, Chao-jiang Gu, Mary Jane Potash & David J. Volsky

  3. Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, OX3 9DS, UK

    Jessie P. Hong & Tomas Hanke

  4. Department of Pathology, New Jersey Medical School, Newark, NJ, 07103, USA

    Leroy R. Sharer

Authors
  1. Jennifer L. Kelschenbach
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  2. Manisha Saini
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  3. Eran Hadas
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  4. Chao-jiang Gu
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  5. Wei Chao
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  6. Galina Bentsman
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  7. Jessie P. Hong
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  8. Tomas Hanke
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  9. Leroy R. Sharer
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  10. Mary Jane Potash
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  11. David J. Volsky
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Corresponding author

Correspondence to David J. Volsky.

Additional information

Jennifer L. Kelschenbach and Manisha Saini contributed equally to this work.

Work in this manuscript was supported by grants AI 079792, DA 017618, MH 083627, and NS 061646-01A1 from the National Institutes of Health, Public Health Service.

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Kelschenbach, J.L., Saini, M., Hadas, E. et al. Mice Chronically Infected with Chimeric HIV Resist Peripheral and Brain Superinfection: A Model of Protective Immunity to HIV. J Neuroimmune Pharmacol 7, 380–387 (2012). https://doi.org/10.1007/s11481-011-9316-1

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  • DOI: https://doi.org/10.1007/s11481-011-9316-1

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