title: The utilization of humanized mouse models for the study of human retroviral infections.
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 IL2rgamma-/-, and NOD/SCID beta2-microglobulinnull animals. Further efforts at minimizing the response of the innate murine immune system produced the Rag2-/-gammac-/- 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.
authors.affiliation: Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University School of Medicine, Washington, DC 20037, USA. bcmrvv@gwumc.edu
authors.forename: Rachel
authors.initials: R
authors.lastname: Van Duyne
authors.forename: Caitlin
authors.initials: C
authors.lastname: Pedati
authors.forename: Irene
authors.initials: I
authors.lastname: Guendel
authors.forename: Lawrence
authors.initials: L
authors.lastname: Carpio
authors.forename: Kylene
authors.initials: K
authors.lastname: Kehn-Hall
authors.forename: Mohammed
authors.initials: M
authors.lastname: Saifuddin
authors.forename: Fatah
authors.initials: F
authors.lastname: Kashanchi
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency; D004195:Disease Models, Animal; D015497:HIV-1 / Q000254:growth & development; D015368:Human T-lymphotropic virus 1 / Q000254:growth & development; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012192:Retroviridae Infections
chemical_list: D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse
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