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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 EcoHIVexpression 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-? responses to two HIV Gag peptide pools. These findings suggest EcoHIVinfected mice may serve as a useful system to investigate the induction of anti-HIV protective immunity for eventual translation to human beings.

Original languageEnglish (US)
Pages (from-to)380-387
Number of pages8
JournalJournal of Neuroimmune Pharmacology
Volume7
Issue number2
DOIs
StatePublished - Jun 2012

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

Keywords

  • Adaptive immune responses
  • Brain
  • Chimeric HIV
  • HIV neuropathogenesis
  • Mouse model
  • Superinfection

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