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

Retrovirology

Esaki M Shankar³  Marie Larsson⁴  Ravi Dyavar Shetty¹  Vijayakumar Velu² 

[1] Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA;Yerkes National Primate Research Center, 954 gatewood Road, Atlanta 30329, GA, USA;Center of Excellence for Research in AIDS (CERiA), University of Malaya, Lembah Pantai, Kuala Lumpur 50603, Malaysia;Department of Clinical and Experimental Medicine, Division of Molecular Virology, Linkoping University, Linkoping 58185, Sweden

关键词: PD-L1 and PD-L2;    B-cell dysfunction;    T-cell dysfunction;    SIV infection;    PD-1 pathway;    PD-1 blockade;    HIV disease;   

Others  :  1131912
DOI  :  10.1186/s12977-015-0144-x

 received in 2014-08-05, accepted in 2015-01-18,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Velu et al.; licensee BioMed Central.

【 图 表 】

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