Molecular Events Involved in Influenza A Virus-Induced Cell Death.

Quanjiao Chen,Rui Gui

doi:10.3389/fmicb.2021.797789

Abstract

Viral infection usually leads to cell death. Moderate cell death is a protective innate immune response. By contrast, excessive, uncontrolled cell death causes tissue destruction, cytokine storm, or even host death. Thus, the struggle between the host and virus determines whether the host survives. Influenza A virus (IAV) infection in humans can lead to unbridled hyper-inflammatory reactions and cause serious illnesses and even death. A full understanding of the molecular mechanisms and regulatory networks through which IAVs induce cell death could facilitate the development of more effective antiviral treatments. In this review, we discuss current progress in research on cell death induced by IAV infection and evaluate the role of cell death in IAV replication and disease prognosis.

Highlights

Apoptosis, necroptosis, and pyroptosis are the three main patterns of cell death in multicellular organisms, playing vital roles in embryonic development; normal tissue homeostasis; and diseases, such as atherosclerosis, cancer, and neurodegeneration, and in defense reactions against infection (Bellamy et al, 1995; Galluzzi et al, 2008; Fuchs and Steller, 2011; Walsh, 2014; Jorgensen et al, 2017; Gao et al, 2018)
TLR3/4 are significantly upregulated in vivo and in vitro during Influenza A virus (IAV) infection, and MyD88 and TIR-domain-containing adapter-inducing IFN-β (TRIF) can be recruited to activate the downstream signaling molecules IFN regulatory factor 3 and nuclear factor (NF)-κB, which are closely related to inflammation and cell death (Figure 2; Le Goffic et al, 2007; He et al, 2011; Matsumoto et al, 2011; Tsai et al, 2014, 2015; Ma et al, 2020; Bertheloot et al, 2021)
Some in vivo animal experiments have been performed, most of the research on programmed cell death in IAV infection has been based on in vitro experiments, which do not reflect the true course of the IAV infection

Summary

Introduction

Necroptosis, and pyroptosis are the three main patterns of cell death in multicellular organisms, playing vital roles in embryonic development; normal tissue homeostasis; and diseases, such as atherosclerosis, cancer, and neurodegeneration, and in defense reactions against infection (Bellamy et al, 1995; Galluzzi et al, 2008; Fuchs and Steller, 2011; Walsh, 2014; Jorgensen et al, 2017; Gao et al, 2018). The viral protein PB1-F2 encoded by PB1, which is localized in the mitochondria of MDCK cells infected with IAV, has been shown to induce intrinsic apoptosis (type I) (Gibbs et al, 2003; Zamarin et al, 2005). - vRNPs are sensed by DAI/ZBP1, which triggers the downstream cell death signaling pathway (Kuriakose et al, 2016; Thapa et al, 2016).

Results

Conclusion