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Viruses
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PANoptosis in Viral Infection
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PANoptosis in Viral Infection

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: closed (30 April 2025) | Viewed by 8419

Special Issue Editor

Dr. Thirumala-Devi Kanneganti

E-Mail Website
Guest Editor
Center of Excellence for Innate Immunity and Inflammation, Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Interests: innate immunity; pattern recognition receptors; NLRs; caspases; infection; inflammation; cancer; cell death; PANoptosis; PANoptosome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Innate immunity provides a critical first line of defence against infections, including viruses. The sensing of viruses by cytosolic innate immune sensors activates signalling pathways that can drive inflammatory cell death, as well as the production of antiviral interferons and proinflammatory cytokines. While inflammatory cell death can be beneficial to clear viral infections, it can also lead to excess inflammation and pathophysiology; therefore, the tight regulation of cell death in response to viral infections is critical.

This Special Issue on PANoptosis in viral infection focuses on viral sensing and the activation of PANoptosis, a unique, lytic, innate immune, and inflammatory cell death pathway that is driven by caspases as well as RIPKs and regulated by PANoptosome complexes. Multiple PANoptosomes have been identified in response to viral infection, including ZBP1- and AIM2-PANoptosomes. This collection of articles will discuss the cellular and molecular mechanisms of PANoptosis and PANoptosomes, providing new insights into therapeutic targets for antiviral therapies and strategies with which to mitigate immunopathogenesis.

Dr. Thirumala-Devi Kanneganti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

• Viruses
• Inflammation
• PANoptosis
• PANoptosome

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Published Papers (4 papers)

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Research

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11 pages, 1182 KiB  
Article
Chromatin Regulator SMARCA4 Is Essential for MHV-Induced Inflammatory Cell Death, PANoptosis
by R. K. Subbarao Malireddi and Thirumala-Devi Kanneganti
Viruses 2024, 16(8), 1261; https://doi.org/10.3390/v16081261 - 6 Aug 2024
Cited by 1 | Viewed by 1613
Abstract
The innate immune system serves as the first line of defense against β-coronaviruses (β-CoVs), a family of viruses that includes SARS-CoV-2. Viral sensing via pattern recognition receptors triggers inflammation and cell death, which are essential components of the innate immune response that facilitate [...] Read more.
The innate immune system serves as the first line of defense against β-coronaviruses (β-CoVs), a family of viruses that includes SARS-CoV-2. Viral sensing via pattern recognition receptors triggers inflammation and cell death, which are essential components of the innate immune response that facilitate viral clearance. However, excessive activation of the innate immune system and inflammatory cell death can result in uncontrolled release of proinflammatory cytokines, resulting in cytokine storm and pathology. PANoptosis, innate immune, inflammatory cell death initiated by innate immune sensors and driven by caspases and RIPKs through PANoptosome complexes, has been implicated in the pathology of viral infections. Therefore, understanding the molecular mechanisms regulating PANoptosis in response to β-CoV infection is critical for identifying new therapeutic targets that can mitigate disease severity. In the current study, we analyzed findings from a cell death-based CRISPR screen with archetypal β-CoV mouse hepatitis virus (MHV) as the trigger to characterize host molecules required for inflammatory cell death. As a result, we identified SMARCA4, a chromatin regulator, as a putative host factor required for PANoptosis in response to MHV. Furthermore, we observed that gRNA-mediated deletion of Smarca4 inhibited MHV-induced PANoptotic cell death in macrophages. These findings have potential translational and clinical implications for the advancement of treatment strategies for β-CoVs and other infections. Full article
(This article belongs to the Special Issue PANoptosis in Viral Infection)
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Review

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31 pages, 5173 KiB  
Review
Innate Immune Sensors and Cell Death—Frontiers Coordinating Homeostasis, Immunity, and Inflammation in Skin
by Ye Mon Soe, Seen Ling Sim and Snehlata Kumari
Viruses 2025, 17(2), 241; https://doi.org/10.3390/v17020241 - 10 Feb 2025
Viewed by 1124
Abstract
The skin provides a life-sustaining interface between the body and the external environment. A dynamic communication among immune and non-immune cells in the skin is essential to ensure body homeostasis. Dysregulated cellular communication can lead to the manifestation of inflammatory skin conditions. In [...] Read more.
The skin provides a life-sustaining interface between the body and the external environment. A dynamic communication among immune and non-immune cells in the skin is essential to ensure body homeostasis. Dysregulated cellular communication can lead to the manifestation of inflammatory skin conditions. In this review, we will focus on the following two key frontiers in the skin: innate immune sensors and cell death, as well as their cellular crosstalk in the context of skin homeostasis and inflammation. This review will highlight the recent advancements and mechanisms of how these pathways integrate signals and orchestrate skin immunity, focusing on inflammatory skin diseases and skin infections in mice and humans. Full article
(This article belongs to the Special Issue PANoptosis in Viral Infection)
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13 pages, 1194 KiB  
Review
Nucleic Acid Sensor-Mediated PANoptosis in Viral Infection
by Lili Zhu, Zehong Qi, Huali Zhang and Nian Wang
Viruses 2024, 16(6), 966; https://doi.org/10.3390/v16060966 - 16 Jun 2024
Cited by 3 | Viewed by 2678
Abstract
Innate immunity, the first line of host defense against viral infections, recognizes viral components through different pattern-recognition receptors. Nucleic acids derived from viruses are mainly recognized by Toll-like receptors, nucleotide-binding domain leucine-rich repeat-containing receptors, absent in melanoma 2-like receptors, and cytosolic DNA sensors [...] Read more.
Innate immunity, the first line of host defense against viral infections, recognizes viral components through different pattern-recognition receptors. Nucleic acids derived from viruses are mainly recognized by Toll-like receptors, nucleotide-binding domain leucine-rich repeat-containing receptors, absent in melanoma 2-like receptors, and cytosolic DNA sensors (e.g., Z-DNA-binding protein 1 and cyclic GMP-AMP synthase). Different types of nucleic acid sensors can recognize specific viruses due to their unique structures. PANoptosis is a unique form of inflammatory cell death pathway that is triggered by innate immune sensors and driven by caspases and receptor-interacting serine/threonine kinases through PANoptosome complexes. Nucleic acid sensors (e.g., Z-DNA-binding protein 1 and absent in melanoma 2) not only detect viruses, but also mediate PANoptosis through providing scaffold for the assembly of PANoptosomes. This review summarizes the structures of different nucleic acid sensors, discusses their roles in viral infections by driving PANoptosis, and highlights the crosstalk between different nucleic acid sensors. It also underscores the promising prospect of manipulating nucleic acid sensors as a therapeutic approach for viral infections. Full article
(This article belongs to the Special Issue PANoptosis in Viral Infection)
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Other

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15 pages, 1728 KiB  
Perspective
PANoptosis Regulation in Reservoir Hosts of Zoonotic Viruses
by Anantika Chandra and Sannula Kesavardhana
Viruses 2024, 16(11), 1733; https://doi.org/10.3390/v16111733 - 4 Nov 2024
Viewed by 1879
Abstract
Zoonotic viruses originating from reservoir hosts, such as bats and birds, often cause severe illness and outbreaks amongst humans. Upon zoonotic virus transmission, infected cells mount innate immune responses that include the activation of programmed cell death pathways to recruit innate immune cells [...] Read more.
Zoonotic viruses originating from reservoir hosts, such as bats and birds, often cause severe illness and outbreaks amongst humans. Upon zoonotic virus transmission, infected cells mount innate immune responses that include the activation of programmed cell death pathways to recruit innate immune cells to the site of infection and eliminate viral replication niches. Different inflammatory and non-inflammatory cell death pathways, such as pyroptosis, apoptosis, necroptosis, and PANoptosis can undergo concurrent activation in humans leading to mortality and morbidity during zoonosis. While controlled activation of PANoptosis is vital for viral clearance during infection and restoring tissue homeostasis, uncontrolled PANoptosis activation results in immunopathology during zoonotic virus infections. Intriguingly, animal reservoirs of zoonotic viruses, such as bats and birds, appear to have a unique immune tolerance adaptation, allowing them to host viruses without succumbing to disease. The mechanisms facilitating high viral tolerance in bats and birds are poorly understood. In this perspective review, we discuss the regulation of PANoptotic pathways in bats and birds and indicate how they co-exist with viruses with mild clinical signs and no immunopathology. Understanding the PANoptotic machinery of bats and birds may thus assist us in devising strategies to contain zoonotic outbreaks amongst humans. Full article
(This article belongs to the Special Issue PANoptosis in Viral Infection)
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