Abstract
Engraftment of immunodeficient mice with a human immune system (humanized mice) provides a model system to study pathogens that target human immune cells. Humanized Rag2−/−γc−/− mice produce the major target cells of HIV-1 and these cells can be detected in primary and secondary lymphoid tissues, as well as in the vaginal and rectal mucosa and brain tissues. This humanized model has already yielded important findings on HIV-1 transmission, mechanisms of pathogenesis, and testing of novel antiviral strategies in vivo. Here, we describe the methods used to infect humanized mice with HIV-1 and to characterize plasma viral load and blood CD4+ T cell depletion.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Berges BK, Rowan MR (2011) The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment. Retrovirology 8:65
Mosier DE (1996) Human immunodeficiency virus infection of human cells transplanted to severe combined immunodeficient mice. Adv Immunol 63:79–125
Jamieson BD, Aldrovandi GM, Zack JA (1996) The SCID-hu mouse: an in-vivo model for HIV-1 pathogenesis and stem cell gene therapy for AIDS. Semin Immunol 8:215–221
Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7:118–130
Legrand N, Ploss A, Balling R, Becker PD, Borsotti C, Brezillon N, Debarry J, de Jong Y, Deng H, Di Santo JP, Eisenbarth S, Eynon E, Flavell RA, Guzman CA, Huntington ND, Kremsdorf D, Manns MP, Manz MG, Mention JJ, Ott M, Rathinam C, Rice CM, Rongvaux A, Stevens S, Spits H, Strick-Marchand H, Takizawa H, van Lent AU, Wang C, Weijer K, Willinger T, Ziegler P (2009) Humanized mice for modeling human infectious disease: challenges, progress, and outlook. Cell Host Microbe 6:5–9
Traggiai E, Chicha L, Mazzucchelli L, Bronz L, Piffaretti JC, Lanzavecchia A, Manz MG (2004) Development of a human adaptive immune system in cord blood cell-transplanted mice. Science 304:104–107
Berges BK, Wheat WH, Palmer B, Connick E, Akkina R (2006) HIV-1 infection and CD4 T cell depletion in the humanized Rag2-/-gc-/- (RAG-hu) mouse model. Retrovirology 3:76
Baenziger S, Tussiwand R, Schlaepfer E, Mazzucchelli L, Heikenwalder M, Kurrer MO, Behnke S, Frey J, Oxenius A, Joller H, Aguzzi A, Manz MG, Speck RF (2006) Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-gc-/- mice. Proc Natl Acad Sci U S A 103:15951–15956
Gorantla S, Makarov E, Finke-Dwyer J, Castanedo A, Holguin A, Gebhart CL, Gendelman HE, Poluektova L (2011) Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis. Am J Pathol 177:2938–2949
Dash PK, Gorantla S, Gendelman HE, Knibbe J, Casale GP, Makarov E, Epstein AA, Gelbard HA, Boska MD, Poluektova LY (2011) Loss of neuronal integrity during progressive HIV-1 infection of humanized mice. J Neurosci 31:3148–3157
Berges BK, Akkina SR, Folkvord JM, Connick E, Akkina R (2008) Mucosal transmission of R5 and X4 tropic HIV-1 via vaginal and rectal routes in humanized Rag2-/-gc-/- (RAG-hu) mice. Virology 373:342–351
Choudhary SK, Rezk NL, Ince WL, Cheema M, Zhang L, Su L, Swanstrom R, Kashuba AD, Margolis DM (2009) Suppression of HIV-1 viremia with reverse transcriptase and integrase inhibitors, CD4+ T cell recovery, and viral rebound upon therapy interruption in a new model for HIV treatment in the humanized Rag2-/- c-/- mice. J Virol 83:8254–8258
Berges BK, Akkina SR, Remling L, Akkina R (2010) Humanized Rag2(-/-) gammac(-/-) (RAG-hu) mice can sustain long-term chronic HIV-1 infection lasting more than a year. Virology 397:100–103
Gartner S, Markovits P, Markovitz DM, Kaplan MH, Gallo RC, Popovic M (1986) The role of mononuclear phagocytes in HTLV-III/LAV infection. Science 233(4760):215–219
Rouet F, Ekouevi DK, Chaix ML, Burgard M, Inwoley A, Tony TD, Danel C, Anglaret X, Leroy V, Msellati P, Dabis F, Rouzioux C (2005) Transfer and evaluation of an automated, low-cost real-time reverse transcription-PCR test for diagnosis and monitoring of human immunodeficiency virus type 1 infection in a West African resource-limited setting. J Clin Microbiol 43:2709–2717
Acknowledgment
This work was supported by a Mentoring Environment Grant from Brigham Young University.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Sanchez, F.M., Berges, B.K. (2013). Characterization of HIV-1 Infection in the Humanized Rag2−/−γc−/− Mouse Model. In: Allen, I. (eds) Mouse Models of Innate Immunity. Methods in Molecular Biology, vol 1031. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-481-4_24
Download citation
DOI: https://doi.org/10.1007/978-1-62703-481-4_24
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-480-7
Online ISBN: 978-1-62703-481-4
eBook Packages: Springer Protocols