Humanized Rag2(-/-)gammac(-/-) (RAG-hu) mice can sustain long-term chronic HIV-1 infection lasting more than a year

Virology. 2010 Feb 5;397(1):100-3. doi: 10.1016/j.virol.2009.10.034. Epub 2009 Nov 18.


HIV-1 infection is characterized by life-long viral persistence and continued decline of helper CD4 T cells. The new generation of humanized mouse models that encompass RAG-hu, hNOG and BLT mice have been shown to be susceptible to HIV-1 infection and display CD4 T cell loss. Productive infection has been demonstrated with both R5 and X4 tropic strains of HIV-1 via direct injection as well as mucosal exposure. However the duration of infection in these mice was evaluated for a limited time lasting only weeks post infection, and it is not established how long the viremia can be sustained, and if the CD4 T cell loss persists throughout the life of the infected humanized mice. In the present study we followed the HIV-1 infected RAG-hu mice to determine the long-term viral persistence and CD4 T cell levels. Our results showed that viremia persists life-long lasting for more than a year, and that CD4 T cell levels display a continuous declining trend as seen in the human. These studies provide a chronic HIV-1 infection humanized mouse model that can be used to dissect viral latency, long-term drug evaluation and immune-based therapies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4 Lymphocyte Count
  • DNA-Binding Proteins / deficiency*
  • Disease Models, Animal*
  • HIV Infections / immunology*
  • HIV Infections / virology*
  • HIV-1 / growth & development
  • HIV-1 / immunology
  • HIV-1 / pathogenicity*
  • Humans
  • Immunoglobulin gamma-Chains / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, SCID
  • Time Factors
  • Viral Load


  • DNA-Binding Proteins
  • Immunoglobulin gamma-Chains
  • Rag2 protein, mouse