Book Review: Humanized Mice for HIV Research


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HIV researchers have been challenged in finding a suitable small animal model, as rodents such as mice and rats cannot be infected by HIV. Existing animal models such as chimpanzees are not ideal as they are expensive, more challenging to work with and have a higher ethical burden for use. Furthermore, while some non-human primates (NHPs) can be infected with HIV, they do not develop similar disease as in humans.

Mice with Human Immune Systems Fill a Critical Gap

A related virus, SIV, is thus typically used to model HIV in NHPs. In this challenging environment, mice with human immune systems fill a critical gap, serving as a small animal model which can be infected with HIV and model the disease. In the Foreword to the new textbook Humanized Mice for HIV Research, Susan Swindells says, "Humanized mice have evolved into an invaluable alternative to SIV-based nonhuman primate models, as they are simpler, less costly, and also highly susceptible to HIV infection."

Modeling of HIV in Mice

Modeling of HIV in mice engrafted with human immune cells got its start in the late 1980's with the development of the scid-hu thy/liv model1 by Mike McCune. The field has made huge advances since then, with the development of super immunodeficient mice such as the NOG mouse contributing significantly to the development of better models of the human immune system.

Humanized Mice for HIV Research

Humanized Mice for HIV Research is a comprehensive overview of human immune engrafted mouse models as they apply to HIV, but also with relevance to other fields of study. Chapters contributed by Mamoru Ito, Mike McCune and Lenny Shultz introduce the history of immune engrafted mice. A chapter by Paul Denton, Tomonori Nochi and J. Victor Garcia has an interesting discussion of the NOD scid relative to NOG/NSG models for immune engraftment. In terms of reconstitution of intestinal lymphoid tissues, the NOD scid offers some key advantages. The function of human cells reconstituted in immune deficient hosts is explored by several contributors, with chapters covering T, B and NK cells as well as antigen presenting cells such as macrophages and dendritic cells.

Relative reconstitution in the lymphoid organs of different humanized mice

Humanization Protocol BLT hHSC transplant only
Mouse Strain(s) NOD scid NOD scid Il2rg NOD scid Il2rg
Rag2 Ilrg
NOD scid
Bone Marrow        
Mouse Thymus Vestigial     Vestigial
Human Thymus     Not Present Not Present
Spleen        
Lymph Nodes        

Intestines
    NOD scid Il2rg  
Rag2 Il2rg
         
Legend Fully humanized Marginally humanized Human cells uncommon Not reported
Adapted from Humanized Mice for HIV Research (New York: Springer-Verlag, 2014).

Some of the most interesting work using immune engrafted mice to model HIV has been transmission studies. These models can be used to study oral, vaginal and rectal transmission of HIV, and they have been used to study many different types of prophylactic approaches. Immune engrafted mice have also been used to model HIV latency and test methods of overcoming such latency. A section of the book is devoted specifically to HIV therapeutic development; this includes practical discussions of species differences in pharmacokinetics, pharmacodynamics and drug distribution. Although the work is titled Humanized Mice for HIV Research, this book also includes a section on modeling other human specific/selection pathogens in human immune system mice. Pathogens covered include dengue, Epstein-Barr virus, HTLV-1, malaria and others.

Humanized Mice for HIV Research is an excellent reference, not just for HIV researchers, but also for anyone interested in working with immune engrafted models. The sections on characterization of the models provide valuable insights applicable to studies in other areas such as tumor immunology. As Victor Garcia says in the concluding chapter, "The availability of these models has completely transformed the landscape in the fields of human immunology and infectious diseases...More recent uses in other areas are beginning to demonstrate the utility and the promise of great future potential applications."

Humanized Mice for HIV Research is available from Springer in both ebook and hardcover versions.


1McCune JM, Namikawa R, Kaneshima H, Shultz LD, Lieberman M, Weissman IL.(1988) The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science. 241(4873):1632-9.