Animal models for viral infection and cell exhaustion

• Type of Material: Article
• Authors: Colleen S. McGary, Emory University; Guido Silvestri, Emory University; Mirko Paiardini, Emory University
• Language: English
• Date: 2014-09-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Wolters Kulwer Health.
• Final Published Version (URL): http://dx.doi.org/10.1097/COH.0000000000000093
• Title of Journal or Parent Work: Current Opinion in HIV and AIDS
• ISSN: 1746-630X
• Volume: 9
• Issue: 5
• Start Page: 492
• End Page: 499
• Grant/Funding Information: In addition, M.P. is supported by grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R01-AI110334 and R21-AI104278.; This work was supported by Public Health Service (PHS) grants RR000165/OD011132 to the Yerkes National Primate Research Center.; G.S. is supported by grants from the NIAID/NIH under award numbers R37 AI-066998 and R01-AI090797.
• Keywords: PROLIFERATIVE CAPACITY; HIV-INFECTION; animal models; ANTIRETROVIRAL THERAPY; PROGRAMMED DEATH-1; nonhuman primates; Science & Technology; IMMUNE-SYSTEM; SIV; Life Sciences & Biomedicine; programmed death-1; humanized mice; DISEASE PROGRESSION; REGULATORY T-CELLS; IN-VIVO BLOCKADE; Infectious Diseases; HUMAN-IMMUNODEFICIENCY-VIRUS; Immunology; PD-1 EXPRESSION
• Research Categories: Health Sciences, Public Health; Health Sciences, Immunology

Abstract

PURPOSE OF REVIEW: Despite eliciting an early antiviral T cell response, HIV-specific T cells are unable to prevent disease progression, partly because of their loss of effector functions, known as T cell exhaustion. Restoring this T cell functionality represents a critical step for regaining immunological control of HIV-1 replication, and may be fundamental for the development of a functional cure for HIV. In this context, the use of animal models is invaluable for evaluating the efficacy and mechanisms of novel therapeutics aimed at reinvigorating T cell functions. RECENT FINDINGS: Although nonhuman primates continue to be a mainstay for studying HIV pathogenesis and therapies, recent advances in humanized mouse models have improved their ability to recapitulate the features of cell exhaustion during HIV infection. Targeting coinhibitory receptors in HIV-infected and simian immunodeficiency virus (SIV)-infected animals has resulted in viral load reductions, presumably by reinvigorating the effector functions of T cells. Additionally, studies combining programmed death-1 (PD-1) blockade with suppressive antiretroviral therapy provide further support to the use of coinhibitory receptor blockades in restoring T cell function by delaying viral load rebound upon antiretroviral therapy interruption. Future in-vivo studies should build on recent in-vitro data, supporting the simultaneous targeting of multiple regulators of cell exhaustion. SUMMARY: In this review, we describe the most recent advances in the use of animal models for the study of cell exhaustion following HIV/SIV infection. These findings suggest that the use of animal models is increasingly critical in translating immunotherapeutics into clinical practice.