Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 22, 2023

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, the major aetiological agent that causes severe clinical and intestinal pathological damage in pigs, it has caused significant economic losses to swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides host immune-related molecules facilitate replication immune evasion. Here, we demonstrated SADS-CoV nsp5 significantly inhibits Sendai virus (SEV)-induced production of IFN-β inflammatory cytokines. targets mRNA-decapping enzyme 1a (DCP1A) via its protease activity inhibit IRF3 NF-κB signaling pathways order decrease cytokine production. We found histidine 41 cystine 144 residues are critical for cleavage activity. Additionally, form DCP1A with mutation glutamine 343 residue resistant nsp5-mediated stronger ability infection than wild-type DCP1A. In conclusion, our findings reveal an important interferon antagonist enhance understanding evasion by alpha coronaviruses.

Language: Английский

---

Epitopes screening and vaccine molecular design of SADS-CoV based on immunoinformatics

Frontiers in Veterinary Science, Journal Year: 2023, Volume and Issue: 9

Published: March 2, 2023

The regional outbreak of the Swine acute diarrhea syndrome coronavirus (SADS-CoV) has seriously threatened swine industry. There is an urgent need to discover safe and effective vaccines contain them quickly. spike protein mediates virus entry into host cells, one most important antigenic determinants a potential vaccine target. Therefore, this study aims conduct predictive analysis epitope S B cells T (MHC class I II) by immunoinformatics methods screening identifying protective epitopes that induce major neutralized antibodies activate immune responses construct vaccines. explored primary, secondary, tertiary structures, disulfide bonds, docking, response simulation, seamless cloning results show dominant high conservativeness coverage IFN-γ, IL-4-positive Th epitope, CTL epitope. constructed interacts stably with TLR-3 receptors, simulation shows good immunogenicity, which could effectively humoral cellular immunity. After codon optimization, it was highly likely be efficiently expressed in Escherichia coli K12 expression system. will provide new theoretical basis for design SADS-CoV antiviral drugs related research on coronaviruses such as SARS-CoV-2.

Language: Английский

---

Identification of TMEM53 as a novel SADS-CoV restriction factor that targets viral RNA-dependent RNA polymerase

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(2)

Published: Aug. 16, 2023

Zoonotic transmission of coronaviruses (CoVs) poses a serious public health threat. Swine acute diarrhea syndrome coronavirus (SADS-CoV), originating from bat HKU2-related CoV, causes devastating swine diseases and high risk spillover to humans. Currently, licensed therapeutics that can prevent potential human outbreaks are unavailable. Identifying the cellular proteins restrict viral infection is imperative for developing effective interventions therapeutics. We utilized large-scale cDNA screening identified transmembrane protein 53 (TMEM53) as novel cell-intrinsic SADS-CoV restriction factor. The inhibitory effect TMEM53 on was found be independent canonical type I interferon responses. Instead, interacts with non-structural 12 (NSP12) disrupts RNA-dependent RNA polymerase (RdRp) complex assembly by interrupting NSP8-NSP12 interaction, thus suppressing RdRp activity synthesis. Deleting domain resulted in abrogation TMEM53-NSP12 interaction antiviral activity. Importantly, exhibited broad against multiple CoVs. Our findings reveal role pave way host-directed CoV infection.

Language: Английский

---

Monitoring emerging pathogens using negative nucleic acid test results from endemic pathogens in pig populations: Application to porcine enteric coronaviruses

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(7), P. e0306532 - e0306532

Published: July 5, 2024

This study evaluated the use of endemic enteric coronaviruses polymerase chain reaction (PCR)-negative testing results as an alternative approach to detect emergence animal health threats with similar clinical diseases presentation. retrospective study, conducted in United States, used PCR-negative from porcine samples tested at six veterinary diagnostic laboratories. As a proof concept, database was first searched for transmissible gastroenteritis virus (TGEV) negative submissions between January 1 st , 2010, through April 29 th 2013, when epidemic diarrhea (PEDV) case diagnosed. Secondly, TGEV- and PEDV-negative were delta coronavirus (PDCoV) 2014. Lastly, encountered best detection algorithms implemented prospectively monitor 2023 coronavirus-negative submissions. Time series (weekly TGEV-negative counts) Seasonal Autoregressive-Integrated Moving-Average (SARIMA) control outliers, trends, seasonality. The SARIMA’s fitted residuals then subjected anomaly (EARS, EWMA, CUSUM, Farrington) identify alarms, defined weeks higher TGEV-negativity than what predicted by models preceding PEDV emergence. best-performing had lowest false alarms (number detected during baseline) highest time alarm emergence). Farrington flexible using SARIMA values, having lower rate identified 4 17 before PDCoV emergences. No results. negative-based monitoring system functioned propagating presence concurrent It demonstrated its applicability additional tool data emergent pathogens disease monitored pathogens.

Language: Английский

---

Mapping the heterogeneous removal landscape of wastewater virome in effluents of different advanced wastewater treatment systems of swine farm

Water Research, Journal Year: 2024, Volume and Issue: 266, P. 122446 - 122446

Published: Sept. 13, 2024

Language: Английский

---