Key Components of Inflammasome and Pyroptosis Pathways Are Deficient in Canines and Felines, Possibly Affecting Their Response to SARS-CoV-2 Infection

Cui, Hongyuan; Zhang, Leiliang

doi:10.3389/fimmu.2020.592622

Cited by 20 publications

(21 citation statements)

References 45 publications

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“…Accordingly, only mild-to-moderate pathological changes such as interstitial pneumonia and bronchiolitis were detected in the respiratory tract of experimentally infected cats [ 19 , 28 ], whereas severe pathological alterations including necrotic changes were observed in human patients with lower respiratory tract infections [ 29 , 30 ]. It has been suggested that deficiencies of key components of the inflammasome and pyroptosis pathway are responsible for the mild symptomatology observed in cats [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

The Upper Respiratory Tract of Felids Is Highly Susceptible to SARS-CoV-2 Infection

Krüger

Rocha

Runft

et al. 2021

IJMS

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Natural or experimental infection of domestic cats and virus transmission from humans to captive predatory cats suggest that felids are highly susceptible to SARS-CoV-2 infection. However, it is unclear which cells and compartments of the respiratory tract are infected. To address this question, primary cell cultures derived from the nose, trachea, and lungs of cat and lion were inoculated with SARS-CoV-2. Strong viral replication was observed for nasal mucosa explants and tracheal air–liquid interface cultures, whereas replication in lung slices was less efficient. Infection was mainly restricted to epithelial cells and did not cause major pathological changes. Detection of high ACE2 levels in the nose and trachea but not lung further suggests that susceptibility of feline tissues to SARS-CoV-2 correlates with ACE2 expression. Collectively, this study demonstrates that SARS-CoV-2 can efficiently replicate in the feline upper respiratory tract ex vivo and thus highlights the risk of SARS-CoV-2 spillover from humans to felids.

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Section: Discussionmentioning

confidence: 99%

The Upper Respiratory Tract of Felids Is Highly Susceptible to SARS-CoV-2 Infection

Krüger

Rocha

Runft

et al. 2021

IJMS

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“…GSDMB is the most divergent member of the GSDM family. Although it is not present in the mouse and rat genomes, felines (cats and tigers) and canines (dogs) contain a Gsdmb orthologue ( 45 ). As shown in the study, human GSDMB is cleaved by chloroquine down-regulate caspase-1 (CASP1) and granzyme A at D236 and K244, respectively, whereas dogs, cats and tigers do not possess these key residues.…”

Section: Gsdm Gene Family In Humans and Micementioning

confidence: 99%

The Versatile Gasdermin Family: Their Function and Roles in Diseases

et al. 2021

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The gasdermin (GSDM) family, a novel group of structure-related proteins, consists of GSDMA, GSDMB, GSDMC, GSDMD, GSDME/DNFA5, and PVJK/GSDMF. GSDMs possess a C-terminal repressor domain, cytotoxic N-terminal domain, and flexible linker domain (except for GSDMF). The GSDM-NT domain can be cleaved and released to form large oligomeric pores in the membrane that facilitate pyroptosis. The emerging roles of GSDMs include the regulation of various physiological and pathological processes, such as cell differentiation, coagulation, inflammation, and tumorigenesis. Here, we introduce the basic structure, activation, and expression patterns of GSDMs, summarize their biological and pathological functions, and explore their regulatory mechanisms in health and disease. This review provides a reference for the development of GSDM-targeted drugs to treat various inflammatory and tissue damage-related conditions.

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“…The gene encoding the inflammasome stimulatory protein NLRP3 is conserved in carnivorans ( 15 ). To determine whether NLRP3 is operational in carnivoran cells, we primed canine monocyte-derived macrophages (MDMs) (fig.…”

Section: Resultsmentioning

confidence: 99%

Evolution-inspired redesign of the LPS receptor caspase-4 into an interleukin-1β–converting enzyme

2021

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Innate immune signaling pathways comprise multiple proteins that promote inflammation. This multistep means of information transfer suggests that complexity is a prerequisite for pathway design. Here, we test this hypothesis by studying caspases that regulate inflammasome-dependent inflammation. Several caspases differ in their ability to recognize bacterial lipopolysaccharide (LPS) and cleave interleukin-1β (IL-1β). No caspase is known to contain both activities, yet distinct caspases with complementary activities bookend an LPS-induced pathway to IL-1β cleavage. Using caspase-1/4 hybrid proteins present in canines as a guide, we identified molecular determinants of IL-1β cleavage specificity within human and murine caspase-1. This knowledge enabled the redesign of human caspase-4 to operate as a one-protein signaling pathway, which intrinsically links LPS detection to IL-1β cleavage and release, independent of inflammasomes. We identified caspase-4 homologs in multiple carnivorans that display the activities of redesigned human caspase-4. These findings illustrate natural signaling pathway diversity and highlight how multistep innate immune pathways can be condensed into a single protein.

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Key Components of Inflammasome and Pyroptosis Pathways Are Deficient in Canines and Felines, Possibly Affecting Their Response to SARS-CoV-2 Infection

Cited by 20 publications

References 45 publications

The Upper Respiratory Tract of Felids Is Highly Susceptible to SARS-CoV-2 Infection

The Upper Respiratory Tract of Felids Is Highly Susceptible to SARS-CoV-2 Infection

The Versatile Gasdermin Family: Their Function and Roles in Diseases

Evolution-inspired redesign of the LPS receptor caspase-4 into an interleukin-1β–converting enzyme

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