Skip Navigation LinksHome > September 2014 - Volume 9 - Issue 5 > Animal models for viral infection and cell exhaustion
Current Opinion in HIV & AIDS:
doi: 10.1097/COH.0000000000000093
CELL EXHAUSTION IN HIV-1 INFECTION: Edited by Daniel E. Kaufmann and Nabila Seddiki

Animal models for viral infection and cell exhaustion

McGary, Colleen S.a,b; Silvestri, Guidoa,b; Paiardini, Mirkoa,b

Collapse Box

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.

© 2014 Lippincott Williams & Wilkins, Inc.

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.