Emerging Role of ZBP1 in Z-RNA Sensing, Influenza Virus-Induced Cell Death, and Pulmonary Inflammation

ABSTRACT Influenza viruses cause respiratory tract infections, which lead to human disease outbreaks and pandemics. Influenza A virus (IAV) circulates in diverse animal species, predominantly aquatic birds. This often results in the emergence of novel viral strains causing severe human disease upon...

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Main Authors: Sharath Basavaraju, Sanchita Mishra, Rashi Jindal, Sannula Kesavardhana
Format: Article
Language:English
Published: American Society for Microbiology 2022-06-01
Series:mBio
Subjects:
Online Access:https://journals.asm.org/doi/10.1128/mbio.00401-22
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author Sharath Basavaraju
Sanchita Mishra
Rashi Jindal
Sannula Kesavardhana
author_facet Sharath Basavaraju
Sanchita Mishra
Rashi Jindal
Sannula Kesavardhana
author_sort Sharath Basavaraju
collection DOAJ
description ABSTRACT Influenza viruses cause respiratory tract infections, which lead to human disease outbreaks and pandemics. Influenza A virus (IAV) circulates in diverse animal species, predominantly aquatic birds. This often results in the emergence of novel viral strains causing severe human disease upon zoonotic transmission. Innate immune sensing of the IAV infection promotes host cell death and inflammatory responses to confer antiviral host defense. Dysregulated respiratory epithelial cell death and excessive proinflammatory responses drive immunopathology in highly pathogenic influenza infections. Here, we discuss the critical mechanisms regulating IAV-induced cell death and proinflammatory responses. We further describe the essential role of the Z-form nucleic acid sensor ZBP1/DAI and RIPK3 in triggering apoptosis, necroptosis, and pyroptosis during IAV infection and their impact on host defense and pathogenicity in vivo. We also discuss the functional importance of ZBP1-RIPK3 signaling in recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viral infections. Understanding these mechanisms of RNA virus-induced cytopathic and pathogenic inflammatory responses is crucial for targeting pathogenic lung infections and human respiratory illness.
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spelling doaj.art-8f1b6ce30bd6405a9592f41c3cdb76712022-12-22T00:20:04ZengAmerican Society for MicrobiologymBio2150-75112022-06-0113310.1128/mbio.00401-22Emerging Role of ZBP1 in Z-RNA Sensing, Influenza Virus-Induced Cell Death, and Pulmonary InflammationSharath Basavaraju0Sanchita Mishra1Rashi Jindal2Sannula Kesavardhana3Department of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, IndiaDepartment of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, IndiaDepartment of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, IndiaDepartment of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, IndiaABSTRACT Influenza viruses cause respiratory tract infections, which lead to human disease outbreaks and pandemics. Influenza A virus (IAV) circulates in diverse animal species, predominantly aquatic birds. This often results in the emergence of novel viral strains causing severe human disease upon zoonotic transmission. Innate immune sensing of the IAV infection promotes host cell death and inflammatory responses to confer antiviral host defense. Dysregulated respiratory epithelial cell death and excessive proinflammatory responses drive immunopathology in highly pathogenic influenza infections. Here, we discuss the critical mechanisms regulating IAV-induced cell death and proinflammatory responses. We further describe the essential role of the Z-form nucleic acid sensor ZBP1/DAI and RIPK3 in triggering apoptosis, necroptosis, and pyroptosis during IAV infection and their impact on host defense and pathogenicity in vivo. We also discuss the functional importance of ZBP1-RIPK3 signaling in recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viral infections. Understanding these mechanisms of RNA virus-induced cytopathic and pathogenic inflammatory responses is crucial for targeting pathogenic lung infections and human respiratory illness.https://journals.asm.org/doi/10.1128/mbio.00401-22influenzainflammationcell deathZBP1Z-RNASARS-CoV-2
spellingShingle Sharath Basavaraju
Sanchita Mishra
Rashi Jindal
Sannula Kesavardhana
Emerging Role of ZBP1 in Z-RNA Sensing, Influenza Virus-Induced Cell Death, and Pulmonary Inflammation
mBio
influenza
inflammation
cell death
ZBP1
Z-RNA
SARS-CoV-2
title Emerging Role of ZBP1 in Z-RNA Sensing, Influenza Virus-Induced Cell Death, and Pulmonary Inflammation
title_full Emerging Role of ZBP1 in Z-RNA Sensing, Influenza Virus-Induced Cell Death, and Pulmonary Inflammation
title_fullStr Emerging Role of ZBP1 in Z-RNA Sensing, Influenza Virus-Induced Cell Death, and Pulmonary Inflammation
title_full_unstemmed Emerging Role of ZBP1 in Z-RNA Sensing, Influenza Virus-Induced Cell Death, and Pulmonary Inflammation
title_short Emerging Role of ZBP1 in Z-RNA Sensing, Influenza Virus-Induced Cell Death, and Pulmonary Inflammation
title_sort emerging role of zbp1 in z rna sensing influenza virus induced cell death and pulmonary inflammation
topic influenza
inflammation
cell death
ZBP1
Z-RNA
SARS-CoV-2
url https://journals.asm.org/doi/10.1128/mbio.00401-22
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