title: Mice chronically infected with chimeric HIV resist peripheral and brain superinfection: a model of protective immunity to HIV.
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.
authors: Molecular Virology Division, St. Luke's-Roosevelt Hospital Center, 432 West 58th Street, New York, NY 10019, USA. jlk2152@columbia.edu
authors: Jennifer L
authors: JL
authors: Kelschenbach
authors: Manisha
authors: M
authors: Saini
authors: Eran
authors: E
authors: Hadas
authors: Chao-Jiang
authors: CJ
authors: Gu
authors: Wei
authors: W
authors: Chao
authors: Galina
authors: G
authors: Bentsman
authors: Jessie P
authors: JP
authors: Hong
authors: Tomas
authors: T
authors: Hanke
authors: Leroy R
authors: LR
authors: Sharer
authors: Mary Jane
authors: MJ
authors: Potash
authors: David J
authors: DJ
authors: Volsky
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000821:virology*; D002678:Chimera / Q000276:immunology / Q000821:virology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D015163:Superinfection / Q000276:immunology*