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PANoptosis in Viral Infection: The Missing Puzzle Piece in the Cell Death Field

期刊

JOURNAL OF MOLECULAR BIOLOGY
卷 434, 期 4, 页码 -

出版社

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2021.167249

关键词

viral infection; cell death; inflammasome; inflammation; pyroptosis; apoptosis; necroptosis; PANoptosis; PANoptosome

资金

  1. US National Institutes of Health [AI101935, AI124346, AI160179, AR056296, CA253095]
  2. American Lebanese Syrian Associated Charities

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Viral infections can activate programmed cell death (PCD) pathways, including pyroptosis, apoptosis, and necroptosis. The emerging concept of PANoptosis suggests extensive crosstalk between these PCD pathways. PANoptosis plays a significant role in regulating viral infection, but it can also have different effects on host defense and viral pathogenesis.
In the past decade, emerging viral outbreaks like SARS-CoV-2, Zika and Ebola have presented major challenges to the global health system. Viruses are unique pathogens in that they fully rely on the host cell to complete their lifecycle and potentiate disease. Therefore, programmed cell death (PCD), a key component of the host innate immune response, is an effective strategy for the host cell to curb viral spread. The most well-established PCD pathways, pyroptosis, apoptosis and necroptosis, can be activated in response to viruses. Recently, extensive crosstalk between PCD pathways has been identified, and there is evidence that molecules from all three PCD pathways can be activated during virus infection. These findings have led to the emergence of the concept of PANoptosis, defined as an inflammatory PCD pathway regulated by the PANoptosome complex with key features of pyroptosis, apoptosis, and/or necroptosis that cannot be accounted for by any of these three PCD pathways alone. While PCD is important to eliminate infected cells, many viruses are equipped to hijack host PCD pathways to benefit their own propagation and subvert host defense, and PCD can also lead to the production of inflammatory cytokines and inflammation. Therefore, PANoptosis induced by viral infection contributes to either host defense or viral pathogenesis in context-specific ways. In this review, we will discuss the multi-faceted roles of PCD pathways in controlling viral infections. (C) 2021 Elsevier Ltd. All rights reserved.

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