title: A mouse model for study of systemic HIV-1 infection, antiviral immune responses, and neuroinvasiveness.
abstract: We created a model of HIV-1 infection of conventional mice for investigation of viral replication, control, and pathogenesis. To target HIV-1 to mice, the coding region of gp120 in HIV-1/NL4-3 was replaced with that of gp80 from ecotropic murine leukemia virus, a retrovirus that infects only rodents. The resulting chimeric virus construct, EcoHIV, productively infected murine lymphocytes, but not human lymphocytes, in culture. Adult, immunocompetent mice were readily susceptible to infection by a single inoculation of EcoHIV as shown by detection of virus in splenic lymphocytes, peritoneal macrophages, and the brain. The virus produced in animals was infectious, as shown by passage in culture, and immunogenic, as shown by induction of antibodies to HIV-1 Gag and Tat. A second chimeric virus based on clade D HIV-1/NDK was also highly infectious in mice; it was detected in both spleen and brain 3 wk after tail vein inoculation, and it induced expression of infection response genes, MCP-1, STAT1, IL-1beta, and complement component C3, in brain tissue as determined by quantitative real-time PCR. EcoHIV infection of mice forms a useful model of HIV-1 infection of human beings for convenient and safe investigation of HIV-1 therapy, vaccines, and potentially pathogenesis.
authors.affiliation: Molecular Virology Division, St. Luke's-Roosevelt Hospital Center, Columbia University Medical Center, 432 West 58th Street, New York, NY 10019, USA. mjp6@columbia.edu
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Potash
authors.forename: Wei
authors.initials: W
authors.lastname: Chao
authors.forename: Galina
authors.initials: G
authors.lastname: Bentsman
authors.forename: Nicolae
authors.initials: N
authors.lastname: Paris
authors.forename: Manisha
authors.initials: M
authors.lastname: Saini
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Nitkiewicz
authors.forename: Paula
authors.initials: P
authors.lastname: Belem
authors.forename: Leroy
authors.initials: L
authors.lastname: Sharer
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Brooks
authors.forename: David J
authors.initials: DJ
authors.lastname: Volsky
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology*; D018932:Chemokine CCL2 / Q000235:genetics; D003176:Complement C3 / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D003176:Complement C3; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators
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