Review

The utilization of humanized mouse models for the study of human retroviral infections

Rachel Van Duyne^1* , Caitlin Pedati^2* , Irene Guendel² , Lawrence Carpio² , Kylene Kehn-Hall² , Mohammed Saifuddin³ and Fatah Kashanchi²

¹  Microbiology, Immunology, and Tropical Medicine Program, The George Washington University School of Medicine, Washington, DC 20037, USA

²  Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University School of Medicine, Washington, DC 20037, USA

³  CONRAD, Eastern Virginia Medical School, 1911 Fort Myer Drive, Suite 900, Arlington, VA 22209, USA

author email corresponding author email* Contributed equally

Retrovirology 2009, 6:76doi:10.1186/1742-4690-6-76

Published:	12 August 2009

Abstract

The development of novel techniques and systems to study human infectious diseases in both an in vitro and in vivo settings is always in high demand. Ideally, small animal models are the most efficient method of studying human afflictions. This is especially evident in the study of the human retroviruses, HIV-1 and HTLV-1, in that current simian animal models, though robust, are often expensive and difficult to maintain. Over the past two decades, the construction of humanized animal models through the transplantation and engraftment of human tissues or progenitor cells into immunocompromised mouse strains has allowed for the development of a reconstituted human tissue scaffold in a small animal system. The utilization of small animal models for retroviral studies required expansion of the early CB-17 scid/scid mouse resulting in animals demonstrating improved engraftment efficiency and infectivity. The implantation of uneducated human immune cells and associated tissue provided the basis for the SCID-hu Thy/Liv and hu-PBL-SCID models. Engraftment efficiency of these tissues was further improved through the integration of the non-obese diabetic (NOD) mutation leading to the creation of NODSCID, NOD/Shi-scid IL2rγ^-/-, and NOD/SCID β2-microglobulin^null animals. Further efforts at minimizing the response of the innate murine immune system produced the Rag2^-/-γ_c^-/- model which marked an important advancement in the use of human CD34+ hematopoietic stem cells. Together, these animal models have revolutionized the investigation of retroviral infections in vivo.