The PD-1/PD-L1 Axis and Virus Infections: A Delicate Balance

Abstract

Programmed cell death protein (PD-1) and its ligands play a fundamental role in the evasion of tumor cells from antitumor immunity. Less well appreciated is the fact that the PD-1/PD-L1 axis also regulates antiviral immune responses and is therefore modulated by a number of viruses. Upregulation of PD-1 and its ligands PD-L1 and PD-L2 is observed during acute virus infection and after infection with persistent viruses including important human pathogens such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Experimental evidence suggests that insufficient signaling through the PD-1 pathway promotes immunopathology during acute infection by exaggerating primary T cell responses. If chronic infection is established, however, high levels of PD-1 expression can have unfavorable immunological consequences. Exhaustion and suppression of antiviral immune responses can result in viral immune evasion. The role of the PD-1/PD-L1 axis during viral infections is further complicated by evidence that PD-L1 also mediates inflammatory effects in the acute phase of an immune response. In this review, we discuss the intricate interplay between viruses and the PD-1/PD-L1 axis.

Increased CD95 (Fas) and PD‐1 expression in peripheral blood T lymphocytes in COVID‐19 patients

“…In particular, PD-1 expression in HIV-specific CD4 + and CD8 + lymphocytes is associated with T-cell exhaustion and disease progression. 10 In our study we assessed the expression of the surface markers CD95 and PD-1 in peripheral blood T lymphocytes in COVID-19 patients, also correlating this phenotype with the T-cell maturational pattern.…”

Serum soluble programmed death ligand-1 is correlated with HBsAg level and nucleos(t)ide analogue therapy in chronic hepatitis B

“…The second step of the increased serum sPD-L1 levels, from immunotolerance (CHB-IT) to immunoactivation (CHB-IA), is in concordance with the positive correlation of the intrahepatic expressions of PD-1 and PD-L1 with liver inflammation in CHB [29,30]. Thus, the PD-1/PD-L1 axis, after immunoactivation, is served as an adaption of the host defense to minimize immunopathology [31]. Therefore, the anti PD-1 and anti-PD-L1 treatments may aggravate inflammation or liver damage in CHB.…”

Repurposing anticancer drugs for the management of COVID-19

“…Twenty four participants will be prospectively randomized to receive intravenous tocilizumab plus pembrolizumab or standard treatments (at physician’s choice). The use of ICIs for COVID-19 is essentially intended as immunomodulator, based on the proposed role of PD-L1 axis in the pathogenesis of ARDS and the expedited clearance of SARS-CoV-2 with anti-PD-L1 therapies ( Schönrich et al 2019 ). Accordingly, the studies ongoing are testing these ICIs both for more severe cases, intending to attenuate the exuberant cytokine production ( Shah et al 2019 ) and for mild presentations, to prevent the onset of the hyper-immune pathological response, then dampen the viral replication ( Schönrich et al 2019 ).…”