Journal of Neuroimmune Pharmacology

, Volume 7, Issue 2, pp 380–387

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

  • 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
ORIGINAL ARTICLE

DOI: 10.1007/s11481-011-9316-1

Cite this article as:
Kelschenbach, J.L., Saini, M., Hadas, E. et al. J Neuroimmune Pharmacol (2012) 7: 380. doi:10.1007/s11481-011-9316-1

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.

Keywords

Mouse model Chimeric HIV Superinfection Adaptive immune responses HIV neuropathogenesis Brain 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jennifer L. Kelschenbach
    • 1
    • 2
  • Manisha Saini
    • 1
  • Eran Hadas
    • 1
  • Chao-jiang Gu
    • 1
    • 2
  • Wei Chao
    • 1
  • Galina Bentsman
    • 1
  • Jessie P. Hong
    • 3
  • Tomas Hanke
    • 3
  • Leroy R. Sharer
    • 4
  • Mary Jane Potash
    • 1
    • 2
  • David J. Volsky
    • 1
    • 2
  1. 1.Molecular Virology DivisionSt. Luke’s-Roosevelt Hospital CenterNew YorkUSA
  2. 2.Department of Pathology & Cell BiologyColumbia UniversityNew YorkUSA
  3. 3.Weatherall Institute of Molecular MedicineUniversity of OxfordOxfordUK
  4. 4.Department of PathologyNew Jersey Medical SchoolNewarkUSA

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