scholarly journals Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease

2014 ◽  
Vol 95 (3) ◽  
pp. 614-626 ◽  
Author(s):  
Xingxing Yang ◽  
Xiaojuan Chen ◽  
Guangxing Bian ◽  
Jian Tu ◽  
Yaling Xing ◽  
...  
Keyword(s):  
Middle East ◽  
Nuclear Translocation ◽  
Proteolytic Processing ◽  
Middle East Respiratory Syndrome ◽  
Effective Control ◽  
Cleavage Sites ◽  
Viral Proteases ◽  
N Terminus ◽  
Genomic Studies

The emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe pulmonary disease in humans and represents the second example of a highly pathogenic coronavirus (CoV) following severe acute respiratory syndrome coronavirus (SARS-CoV). Genomic studies revealed that two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), process the polyproteins encoded by the MERS-CoV genomic RNA. We previously reported that SARS-CoV PLpro acts as both deubiquitinase (DUB) and IFN antagonist, but the function of the MERS-CoV PLpro was poorly understood. In this study, we characterized MERS-CoV PLpro, which is a protease and can recognize and process the cleavage sites (CS) of nsp1-2, nsp2-3 and nsp3-4. The LXGG consensus cleavage sites in the N terminus of pp1a/1ab, which is generally essential for CoV PLpro-mediated processing, were also characterized in MERS-CoV. MERS-CoV PLpro, like human SARS-CoV PLpro and NL63-CoV PLP2, is a viral deubiquitinating enzyme. It acts on both K48- and K63-linked ubiquitination and ISG15-linked ISGylation. We confirmed that MERS-CoV PLpro acts as an IFN antagonist through blocking the phosphorylation and nuclear translocation of IFN regulatory factor 3 (IRF3). These findings indicate that MERS-CoV PLpro acts as a viral DUB and suppresses production of IFN-β by an interfering IRF3-mediated signalling pathway, in addition to recognizing and processing the CS at the N terminus of replicase polyprotein to release the non-structural proteins. The characterization of proteolytic processing, DUB and IFN antagonist activities of MERS-CoV PLpro would reveal the interactions between MERS-CoV and its host, and be applicable to develop strategies targeting PLpro for the effective control of MERS-CoV infection.

scholarly journals Real-time characterization of risks of death associated with the Middle East respiratory syndrome (MERS) in the Republic of Korea, 2015

BMC Medicine ◽  
2015 ◽  
Vol 13 (1) ◽  
Author(s):  
Kenji Mizumoto ◽  
Akira Endo ◽  
Gerardo Chowell ◽  
Yuichiro Miyamatsu ◽  
Masaya Saitoh ◽  
...  
Keyword(s):  
Middle East ◽  
Real Time ◽  
Middle East Respiratory Syndrome ◽  
Republic Of Korea ◽  
The Republic

scholarly journals Establishment of well-differentiated camelid airway cultures to study Middle East respiratory syndrome coronavirus

2021 ◽  
Author(s):  
Mitra Gultom ◽  
Annika Kratzel ◽  
Jasmine Portmann ◽  
Hanspeter Stalder ◽  
Astrid Chanfon Baetzner ◽  
...  
Keyword(s):  
Middle East ◽  
Airway Epithelial Cell ◽  
Respiratory Illness ◽  
Middle East Respiratory Syndrome ◽  
Cell Tropism ◽  
Airway Epithelial ◽  
Detailed Characterization ◽  
Well Differentiated ◽  
Severe Respiratory Illness

In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in Saudi Arabia and was mostly associated with severe respiratory illness in humans. Dromedary camels are the zoonotic reservoir for MERS-CoV. To investigate the biology of MERS-CoV in camelids, we developed a well-differentiated airway epithelial cell (AEC) culture model for Llama glama and Camelus bactrianus. Histological characterization revealed progressive epithelial cellular differentiation with well-resemblance to autologous ex vivo tissues. We demonstrate that MERS-CoV displays a divergent cell tropism and replication kinetics profile in both AEC models. Furthermore, we observed that in the camelid AEC models MERS-CoV replication can be inhibited by both type I and III interferons (IFNs). In conclusion, we successfully established camelid AEC cultures that recapitulate the in vivo airway epithelium and reflect MERS-CoV infection in vivo. In combination with human AEC cultures, this system allows detailed characterization of the molecular basis of MERS-CoV cross-species transmission in respiratory epithelium. 

scholarly journals Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 152 ◽  
Author(s):  
Arinjay Banerjee ◽  
Darryl Falzarano ◽  
Noreen Rapin ◽  
Jocelyne Lew ◽  
Vikram Misra
Keyword(s):  
Middle East ◽  
Nuclear Translocation ◽  
Human Cells ◽  
Middle East Respiratory Syndrome ◽  
Poly I:C ◽  
Interferon Response ◽  
Synthetic Analogue ◽  
Post Translational Modifications ◽  
Antiviral Responses ◽  
Interfering Rna

Insectivorous bats are speculated to be ancestral hosts of Middle-East respiratory syndrome (MERS) coronavirus (CoV). MERS-CoV causes disease in humans with thirty-five percent fatality, and has evolved proteins that counteract human antiviral responses. Since bats experimentally infected with MERS-CoV do not develop signs of disease, we tested the hypothesis that MERS-CoV would replicate less efficiently in bat cells than in human cells because of its inability to subvert antiviral responses in bat cells. We infected human and bat (Eptesicus fuscus) cells with MERS-CoV and observed that the virus grew to higher titers in human cells. MERS-CoV also effectively suppressed the antiviral interferon beta (IFNβ) response in human cells, unlike in bat cells. To determine if IRF3, a critical mediator of the interferon response, also regulated the response in bats, we examined the response of IRF3 to poly(I:C), a synthetic analogue of viral double-stranded RNA. We observed that bat IRF3 responded to poly(I:C) by nuclear translocation and post-translational modifications, hallmarks of IRF3 activation. Suppression of IRF3 by small-interfering RNA (siRNA) demonstrated that IRF3 was critical for poly(I:C) and MERS-CoV induced induction of IFNβ in bat cells. Our study demonstrates that innate antiviral signaling in E. fuscus bat cells is resistant to MERS-CoV-mediated subversion.

Middle East Respiratory Syndrome Coronavirus

2021 ◽  
Vol 42 (06) ◽  
pp. 828-838
Author(s):  
Jaffar A. Al-Tawfiq ◽  
Esam I. Azhar ◽  
Ziad A. Memish ◽  
Alimuddin Zumla
Keyword(s):  
Middle East ◽  
Community Education ◽  
Health Workers ◽  
Severe Disease ◽  
Genomic Analysis ◽  
Middle East Respiratory Syndrome ◽  
Control Measures ◽  
World Health ◽  
Effective Control ◽  
Wide Range

AbstractThe past two decades have witnessed the emergence of three zoonotic coronaviruses which have jumped species to cause lethal disease in humans: severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. MERS-CoV emerged in Saudi Arabia in 2012 and the origins of MERS-CoV are not fully understood. Genomic analysis indicates it originated in bats and transmitted to camels. Human-to-human transmission occurs in varying frequency, being highest in healthcare environment and to a lesser degree in the community and among family members. Several nosocomial outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by World Health Organization as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. MERS-CoV has been identified in dromedaries in several countries in the Middle East, Africa, and South Asia. MERS-CoV-2 causes a wide range of clinical presentations, although the respiratory system is predominantly affected. There are no specific antiviral treatments, although recent trials indicate that combination antivirals may be useful in severely ill patients. Diagnosing MERS-CoV early and implementation infection control measures are critical to preventing hospital-associated outbreaks. Preventing MERS relies on avoiding unpasteurized or uncooked animal products, practicing safe hygiene habits in health care settings and around dromedaries, community education and awareness training for health workers, as well as implementing effective control measures. Effective vaccines for MERS-COV are urgently needed but still under development.

scholarly journals Genetic Characterization of Middle East Respiratory Syndrome Coronavirus, South Korea, 2018

2019 ◽  
Vol 25 (5) ◽  
pp. 958-962 ◽  
Author(s):  
Yoon-Seok Chung ◽  
Jeong Min Kim ◽  
Heui Man Kim ◽  
Kye Ryeong Park ◽  
Anna Lee ◽  
...  
Keyword(s):  
Middle East ◽  
South Korea ◽  
Genetic Characterization ◽  
Middle East Respiratory Syndrome

scholarly journals Identification and characterization of Saccharomyces cerevisiae yapsin 3, a new member of the yapsin family of aspartic proteases encoded by the YPS3 gene

1999 ◽  
Vol 339 (2) ◽  
pp. 407-411 ◽  
Author(s):  
Vicki OLSEN ◽  
Niamh X. CAWLEY ◽  
Jakob BRANDT ◽  
Michi EGEL-MITANI ◽  
Y. Peng LOH
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Cleavage Sites ◽  
Basic Residue ◽  
Aspartic Proteases ◽  
N Terminus ◽  
High Degree ◽  
Identification And Characterization ◽  
Degree Of Similarity

A new aspartic protease from Saccharomyces cerevisiae, with a high degree of similarity with yapsin 1 and yapsin 2 and a specificity for basic residue cleavage sites of prohormones, has been cloned. This enzyme was named yapsin 3. Expression of a C-terminally truncated non-membrane anchored yapsin 3 in yeast yielded a heterogeneous protein between 135–200 kDa which, upon treatment with endoglycosidase H, migrated as a 60 kDa form. Amino-acid analysis of the N-terminus of expressed yapsin 3 revealed two different N-terminal residues, serine-48 and phenylalanine-54, which followed a dibasic and a monobasic residue respectively. Cleavage of several prohormones by non-anchored yapsin 3 revealed a specificity distinct from that of yapsin 1.

scholarly journals Correction to: Detection and full genome characterization of two beta CoV viruses related to Middle East respiratory syndrome from bats in Italy

2018 ◽  
Vol 15 (1) ◽  
Author(s):  
Ana Moreno ◽  
Davide Lelli ◽  
Luca De Sabato ◽  
Guendalina Zaccaria ◽  
Arianna Boni ◽  
...  
Keyword(s):  
Middle East ◽  
Middle East Respiratory Syndrome ◽  
Full Genome ◽  
Genome Characterization

scholarly journals Biochemical Characterization of Middle East Respiratory Syndrome Coronavirus Helicase

mSphere ◽  
2016 ◽  
Vol 1 (5) ◽  
Author(s):  
Adeyemi O. Adedeji ◽  
Hilary Lazarus
Keyword(s):  
Middle East ◽  
Nucleic Acids ◽  
Biochemical Characterization ◽  
Atp Hydrolysis ◽  
The United States ◽  
Biochemical Properties ◽  
Middle East Respiratory Syndrome ◽  
Wide Range ◽  
Novel Coronavirus

ABSTRACT Coronaviruses are known to cause a wide range of diseases in humans and animals. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans in the Middle East, Europe, North Africa, and the United States of America. Helicases are motor proteins that catalyze the processive separation of double-stranded nucleic acids into two single-stranded nucleic acids by utilizing the energy derived from ATP hydrolysis. MERS-CoV helicase is one of the most important viral replication enzymes of this coronavirus. Herein, we report the first bacterial expression, enzyme purification, and biochemical characterization of MERS-CoV helicase. The knowledge obtained from this study might be used to identify an inhibitor of MERS-CoV replication, and the helicase might be used as a therapeutic target. Middle East respiratory syndrome coronavirus (MERS-CoV) helicase is a superfamily 1 helicase containing seven conserved motifs. We have cloned, expressed, and purified a Strep-fused recombinant MERS-CoV nonstructural protein 13 (M-nsp13) helicase. Characterization of its biochemical properties showed that it unwound DNA and RNA similarly to severe acute respiratory syndrome CoV nsp13 (S-nsp13) helicase. We showed that M-nsp13 unwound in a 5′-to-3′ direction and efficiently unwound the partially duplex RNA substrates with a long loading strand relative to those of the RNA substrates with a short or no loading strand. Moreover, the Km of ATP for M-nsp13 is inversely proportional to the length of the 5′ loading strand of the partially duplex RNA substrates. Finally, we also showed that the rate of unwinding (ku) of M-nsp13 is directly proportional to the length of the 5′ loading strand of the partially duplex RNA substrate. These results provide insights that enhance our understanding of the biochemical properties of M-nsp13. IMPORTANCE Coronaviruses are known to cause a wide range of diseases in humans and animals. Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans in the Middle East, Europe, North Africa, and the United States of America. Helicases are motor proteins that catalyze the processive separation of double-stranded nucleic acids into two single-stranded nucleic acids by utilizing the energy derived from ATP hydrolysis. MERS-CoV helicase is one of the most important viral replication enzymes of this coronavirus. Herein, we report the first bacterial expression, enzyme purification, and biochemical characterization of MERS-CoV helicase. The knowledge obtained from this study might be used to identify an inhibitor of MERS-CoV replication, and the helicase might be used as a therapeutic target.

Sign in / Sign up

Export Citation Format

Share Document