A mouse model for study of systemic HIV-1 infection, antiviral immune responses, and neuroinvasiveness
| Autor: | Manisha Saini, Nicolae Paris, Mary Jane Potash, Andrew Brooks, Galina Bentsman, Paula Belem, Wei Chao, David J. Volsky, Jadwiga Nitkiewicz, Leroy R. Sharer |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
viruses
Spleen Biology Virus Pathogenesis Mice Immune system Retrovirus Murine leukemia virus medicine Animals RNA Messenger Chemokine CCL2 Acquired Immunodeficiency Syndrome Mice Inbred BALB C Multidisciplinary Brain Complement C3 Biological Sciences biology.organism_classification Virology DNA-Binding Proteins Disease Models Animal medicine.anatomical_structure STAT1 Transcription Factor Viral replication DNA Viral biology.protein HIV-1 Trans-Activators Female Antibody |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 102(10) |
| ISSN: | 0027-8424 |
| Popis: | 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-1β, 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. |
| Databáze: | OpenAIRE |
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