Moving beyond the mousetrap: Current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies

Yash Agarwal, Cole Beatty, Shivkumar Biradar, Isabella Castronova, Sara Ho, Kevin Melody, Moses Turkle Bility

Research output: Contribution to journalReview article

Abstract

The development of safe and effective combination antiretroviral therapies for human immunodeficiency virus (HIV) infection over the past several decades has significantly reduced HIV-associated morbidity and mortality. Additionally, antiretroviral drugs have provided an effective means of protection against HIV transmission. Despite these advances, significant limitations exist; namely, the inability to eliminate HIV reservoirs, the inability to reverse lymphoid tissues damage, and the lack of an effective vaccine for preventing HIV transmission. Evaluation of the safety and efficacy of therapeutics and vaccines for eliminating HIV reservoirs and preventing HIV transmission requires robust in vivo models. Since HIV is a human-specific pathogen, that targets hematopoietic lineage cells and lymphoid tissues, in vivo animal models for HIV-host interactions require incorporation of human hematopoietic lineage cells and lymphoid tissues. In this review, we will discuss the construction of mouse models with human lymphoid tissues and/or hematopoietic lineage cells, termed, human immune system (HIS)-humanized mice. These HIS-humanized mouse models can support the development of functional human innate and adaptive immune cells, along with primary (thymus) and secondary (spleen) lymphoid tissues. We will discuss applications of HIS-humanized mouse models in evaluating the safety and efficacy of therapeutics against HIV reservoirs and associated immunopathology, and delineate the human immune response elicited by candidate HIV vaccines. In addition to focusing on how these HIS-humanized mouse models have already furthered our understanding of HIV and contributed to HIV therapeutics development, we discuss how emerging HIS-humanized rat models could address the limitations of HIS-mouse models.

Original languageEnglish (US)
Article number8
JournalRetrovirology
Volume17
Issue number1
DOIs
StatePublished - Apr 10 2020

Keywords

  • Animal models for HIV vaccines
  • Humanized mouse and rat models
  • In vivo models for HIV cure
  • Modeling HIV infection and reservoir
  • Modeling human anti-HIV immune response

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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