A mouse model for study of systemic HIV-1 infection, antiviral immune responses, and neuroinvasiveness

Mary Jane Potash, Wei Chao, Galina Bentsman, Nicolae Paris, Manisha Saini, Jadwiga Nitkiewicz, Paula Belem, Leroy Sharer, Andrew I. Brooks, David J. Volsky

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

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-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.

Original languageEnglish
Pages (from-to)3760-3765
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number10
DOIs
StatePublished - 8 Mar 2005
Externally publishedYes

Keywords

  • AIDS
  • Animal model
  • Brain
  • Vaccine

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