A mouse model for study of systemic HIV-1 infection, antiviral immune responses, and neuroinvasiveness.
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.
Potash
Mary Jane
MJ
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
Chao
Wei
W
Bentsman
Galina
G
Paris
Nicolae
N
Saini
Manisha
M
Nitkiewicz
Jadwiga
J
Belem
Paula
P
Sharer
Leroy
L
Brooks
Andrew I
AI
Volsky
David J
DJ
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
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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