Humanized Rag2(-/-)gammac(-/-) (RAG-hu) mice can sustain long-term chronic HIV-1 infection lasting more than a year.
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.
Berges
Bradford K
BK
Department of Microbiology, Immunology, and Pathology, Colorado State University, 329 Pathology, Fort Collins, CO 80523, USA. Brad.berges@gmail.com
Akkina
Sarah R
SR
Remling
Leila
L
Akkina
Ramesh
R
D000818:Animals; D018791:CD4 Lymphocyte Count; D004268:DNA-Binding Proteins / Q000172:deficiency*; D004195:Disease Models, Animal; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D013997:Time Factors; D019562:Viral Load
D004268:DNA-Binding Proteins; D007142:Immunoglobulin gamma-Chains; C499308:Rag2 protein, mouse