Virus Infection and Death Receptor-Mediated Apoptosis

Abstract

Virus infection can trigger extrinsic apoptosis. Cell-surface death receptors of the tumor necrosis factor family mediate this process. They either assist persistent viral infection or elicit the elimination of infected cells by the host. Death receptor-mediated apoptosis plays an important role in viral pathogenesis and the host antiviral response. Many viruses have acquired the capability to subvert death receptor-mediated apoptosis and evade the host immune response, mainly by virally encoded gene products that suppress death receptor-mediated apoptosis. In this review, we summarize the current information on virus infection and death receptor-mediated apoptosis, particularly focusing on the viral proteins that modulate death receptor-mediated apoptosis.

Keywords: death receptor; extrinsic apoptosis; host immune response; virus infection.

Figure 1

Viral modulation of death-receptor mediated apoptosis. Death receptors Fas, TRAIL-R and TNF-R form DISC upon binding to their ligands, activate caspase cascade and subsequently initiate extrinsic apoptosis. Caspase-8 activation can cleavage BID to tBID and link to mitochondria-mediated intrinsic apoptosis pathway. Virus infection regulates death receptor-mediated extrinsic apoptosis mainly through virally encoded proteins. The regulatory mechanisms involve: (1) regulating the expression and function of death receptors/ligands; (2) interfering DISC formation and function; (3) regulating caspase activities; (4) regulating the expression and function of pro-apoptotic and anti-apoptotic proteins. Black arrow represents signal induction; grey arrow represents signal induced by viruses; grey T bar represents signal inhibited by viruses.