The Seneca Valley virus 3C protease cleaves DCP1A to attenuate its antiviral effects

Veterinary Research, Journal Year: 2025, Volume and Issue: 56(1)

Published: Feb. 28, 2025

Abstract Seneca Valley virus (SVV), a new member of Picornaviridae , causes idiopathic vesicular symptoms in pregnant sows and acute death neonatal piglets, considerably damaging the swine industry. The viral protease 3C (3C pro ) cleaves host immune-related molecules to create favorable environment for replication. In this study, we found that mRNA decapping enzyme 1A (DCP1A) is novel antiviral effector against SVV infection targets 3D RNA-dependent RNA polymerase OPTN-mediated autophagic degradation. To counteract effect, DCP1A cleavage at glutamine 343 (Q343), resulting cleaved products (1–343) (344–580), which lose ability restrict contrast, cleavage-resistant DCP1A-Q343A mutant exhibited stronger effects than wild-type DCP1A. Additionally, degradation protein targeted by was abolished after its . conclusion, our study demonstrated pivotal ISG antagonist These results offer insight into how viruses evade immunity.

Language: Английский

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NS7a of SADS-CoV promotes viral infection via inducing apoptosis to suppress type III interferon production

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(5)

Published: April 16, 2024

ABSTRACT Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered swine with potential cross-species transmission risk. Although SADS-CoV-induced host cell apoptosis and innate immunity antagonization has been revealed, underlying signaling pathways remain obscure. Here, we demonstrated that infection of SADS-CoV induced in vivo vitro , viral protein NS7a mainly responsible for cells. Furthermore, found interacted apoptosis-inducing factor mitochondria associated 1 (AIFM1) to activate caspase-3 via caspase-6 SADS-CoV-infected cells, enhanced replication. Importantly, suppressed poly(I:C)-induced expression type III interferon (IFN-λ) activating cleave regulatory 3 (IRF3), inhibitor protects piglets against . These findings reveal how inhibit provide valuable clue the development effective drugs clinical control infection. IMPORTANCE Over last 20 years, multiple animal-originated coronaviruses, including severe respiratory (SARS-CoV), middle east (MERS-CoV), SARS-CoV-2, have caused millions deaths, seriously jeopardized human health, hindered social development, indicating study coronaviruses particularly important. Bat-originated (SADS-CoV), 2017, can not only cause fatal piglets, but also infect risk transmission, its pathogenesis unclear. In this study, suppresses IFN-λ production (AIFM1)-caspase-6-caspase-3-interferon (IRF3) pathway, (Z-DEVD-FMK) effectively replication protect infected piglets. Our contribute better understanding SADS-CoV-host interactions as part using apoptosis-inhibitor drug therapeutic approaches prevention

Language: Английский

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Interplay of swine acute diarrhoea syndrome coronavirus and the host intrinsic and innate immunity

Veterinary Research, Journal Year: 2025, Volume and Issue: 56(1)

Published: Jan. 9, 2025

Abstract Swine acute diarrhoea syndrome coronavirus (SADS-CoV), a novel HKU2-related of bat origin, is newly emerged swine enteropathogenic that causes severe in piglets. SADS-CoV has broad cell tropism with the capability to infect wide variety cells from human and diverse animals, which implicates its ability hold high risks cross-species transmission. The intracellular antiviral immunity, comprised intrinsic innate represents first line host defence against viral infection prior onset adaptive immunity. To date, there are no vaccines drugs approved prevent or treat infection. Understanding mutual relationship between immunity crucial for development SADS-CoV. Here, we review recent advancements our understanding interplay extensive in-depth investigation on their interactive will contribute identification new targets developing intervention strategies control

Language: Английский

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Swine Acute Diarrhea Syndrome Coronavirus: An Overview of Virus Structure and Virus–Host Interactions

Animals, Journal Year: 2025, Volume and Issue: 15(2), P. 149 - 149

Published: Jan. 9, 2025

SADS-CoV, a recently identified Rhinolophus bat coronavirus HKU2-associated swine coronavirus, is malignant pathogen that causes acute diarrhea, severe and weight loss in infected piglets. The virus was first detected Guangdong Province, China, 2017 has since been observed Jiangxi, Fujian, Guangxi Provinces. In 2023, the Henan inland China. This can infect various cell lines, including human showing significant potential for cross-species transmission posing possible zoonotic threat. However, molecular biology of SADS-CoV remains largely unknown, there are no commercially available therapeutics or vaccines to prevent infection. this review, an update on progress research provided, with focus history outbreaks, characteristics virus, its interactions host, developments vaccines.

Language: Английский

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The Alpha-coronavirus E protein inhibits the JAK-STAT pathway signaling by triggering STAT2 degradation through OPTN- and NBR1-mediated selective autophagy

Autophagy, Journal Year: 2025, Volume and Issue: unknown

Published: March 16, 2025

The zoonotic transmission of coronaviruses continues to pose a considerable threat humans. Swine acute diarrhea syndrome coronavirus (SADS-CoV), bat related HKU2, causes severe economic losses in the pig industry and has potential trigger outbreaks However, our understanding how SADS-CoV evades host's innate immunity remains limited, hindering effective responses human outbreaks. In this study, we demonstrate that envelope protein (E) inhibits type I interferon (IFN-I) signaling by inducing degradation STAT2 via macroautophagy/autophagy-lysosome pathway. Mechanistically, E host promoting through autophagy, mediated NBR1 OPTN receptors. Notably, ubiquitination is required for autophagic STAT2. Additionally, lysine residue K61 crucial its stable expression; however, it not involved ubiquitination. conclusion, study reveals novel mechanism which disrupts IFN-I targeting enhancing SADS-CoV's immune evasion strategies providing drug targets controlling viral infections.

Language: Английский

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Porcine deltacoronavirus nsp5 antagonizes type I interferon signaling by cleaving IFIT3

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(2)

Published: Jan. 30, 2024

Porcine deltacoronavirus (PDCoV) is a potential emerging zoonotic pathogen, and studies on the prevalence pathogenesis of PDCoV are ongoing. The main protease (nsp5) provides an excellent target for antivirals due to its essential conserved function in viral replication cycle. Previous have revealed that nsp5 antagonizes type I interferon (IFN) production by targeting interferon-stimulated genes. Here, we provide first demonstration IFN signaling cleaving IFIT3, which affects response after infection. Our findings reveal important antagonist enhance understanding immune evasion deltacoronaviruses.

Language: Английский

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