Role of PD-1 co-inhibitory pathway in HIV infection and potential therapeutic options

• Type of Material: Article
• Authors: Vijayakumar Velu, Emory University; Ravi Dyavar Shetty, Emory University; Marie Larsson, Linkoping University; Esaki M. Shankar, University of Malaya
• Language: English
• Date: 2015-02-08
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © Velu et al.; licensee BioMed Central. 2015
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12977-015-0144-x
• Title of Journal or Parent Work: Retrovirology
• ISSN: 1742-4690
• Volume: 12
• Issue: 1
• Start Page: 14
• End Page: 14
• Grant/Funding Information: The authors also acknowledge funding support provided for this work by the University of Malaya Research Grant (UMRG) of the Health and Translational Medicine Research Cluster, University of Malaya, Kuala Lumpur (RP021A-13HTM).; The authors acknowledge funding support provided for this work by Dr. Rama Rao Amara (Emory Vaccine Center) to Dr. Velu from NIH grants R01 A107183, R01A1074417, RC2CA149086.
• Keywords: T-cell dysfunction; PD-L1 and PD-L2; B-cell dysfunction; PD-1 pathway; HIV disease; SIV infection; PD-1 blockade
• Research Categories: Health Sciences, Pharmacology; Biology, Virology

Abstract

Virus-specific CD8+ T cells play an important role in controlling viral infections including human immunodeficiency virus (HIV) infection. However, during chronic HIV infection, virus-specific CD8+ T cells undergo functional exhaustion, lose effector functions and fail to control viral infection. HIV-specific CD8 T cells expressing high levels of co-inhibitory molecule programmed death-1 (PD-1) during the chronic infection and are characterized by lower proliferation, cytokine production, and cytotoxic abilities. Although, antiretroviral therapy has resulted in dramatic decline in HIV replication, there is no effective treatment currently available to eradicate viral reservoirs or restore virus-specific T or B-cell functions that may complement ART in order to eliminate the virus. In recent years, studies in mice and non-human primate models of HIV infection demonstrated the functional exhaustion of virus-specific T and B cells could be reversed by blockade of interaction between PD-1 and its cognate ligands (PD-L1 and PD-L2). In this review, we discuss recent advances in our understanding of PD-1 pathway in HIV/SIV infection and discuss the beneficial effects of PD-1 blockade during chronic HIV/SIV infection and its potential role as immunotherapy for HIV/AIDS.