Detection of #MERS-CoV #antigen on #formalin-fixed paraffin-embedded #nasal #tissue of #alpacas by immunohistochemistry using #human #mAbs directed against different epitopes of the spike protein (Vet Immunol Immunopathol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Vet Immunol Immunopathol. 2019 Sep 9;218:109939. doi: 10.1016/j.vetimm.2019.109939. [Epub ahead of print]

Detection of MERS-CoV antigen on formalin-fixed paraffin-embedded nasal tissue of alpacas by immunohistochemistry using human monoclonal antibodies directed against different epitopes of the spike protein.

Haverkamp AK1, Bosch BJ2, Spitzbarth I3, Lehmbecker A3, Te N4, Bensaid A4, Segalés J5, Baumgärtner W6.

Author information: 1 Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559 Hannover, Germany. 2 Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, the Netherlands. 3 Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559 Hannover, Germany; Center for Systems Neuroscience, 30559 Hannover, Germany. 4 IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain. 5 Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, UAB, 08193 Bellaterra, Barcelona, Spain; UAB, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain. 6 Department of Pathology, University of Veterinary Medicine Hannover Foundation, 30559 Hannover, Germany; Center for Systems Neuroscience, 30559 Hannover, Germany. Electronic address: Wolfgang.Baumgaertner@tiho-hannover.de.

 

Abstract

Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one third of human patients. In recent years, several investigators developed protective antibodies which could be used as prophylaxis in prospective human epidemics. In the current study, eight human monoclonal antibodies (mAbs) with neutralizing and non-neutralizing capabilities, directed against different epitopes of the MERS-coronavirus (MERS-CoV) spike (MERS-S) protein, were investigated with regard to their ability to immunohistochemically detect respective epitopes on formalin-fixed paraffin-embedded (FFPE) nasal tissue sections of MERS-CoV experimentally infected alpacas. The most intense immunoreaction was detected using a neutralizing antibody directed against the receptor binding domain S1B of the MERS-S protein, which produced an immunosignal in the cytoplasm of ciliated respiratory epithelium and along the apical membranous region. A similar staining was obtained by two other mAbs which recognize the sialic acid-binding domain and the ectodomain of the membrane fusion subunit S2, respectively. Five mAbs lacked immunoreactivity for MERS-CoV antigen on FFPE tissue, even though they belong, at least in part, to the same epitope group. In summary, three tested human mAbs demonstrated capacity for detection of MERS-CoV antigen on FFPE samples and may be implemented in double or triple immunohistochemical methods.

Copyright © 2019 Elsevier B.V. All rights reserved.

KEYWORDS: Immunohistochemistry; Middle East respiratory syndrome coronavirus; Monoclonal human antibodies; Spike protein

PMID: 31526954 DOI: 10.1016/j.vetimm.2019.109939

Keywords: MERS-CoV; Monoclonal antibodies; Diagnostic tests.

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#Diversity of dromedary #camel #coronavirus #HKU23 in #African camels revealed multiple #recombination events among closely related #Betacoronaviruses of the subgenus #Embecovirus (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

Diversity of dromedary camel coronavirus HKU23 in African camels revealed multiple recombination events among closely related Betacoronaviruses of the subgenus Embecovirus.

Ray T. Y. So, Daniel K. W. Chu, Eve Miguel, Ranawaka A. P. M. Perera, Jamiu O. Oladipo, Ouafaa Fassi-Fihri, Gelagay Aylet, Ronald L. W. Ko, Ziqi Zhou, Mo-Sheung Cheng, Sulyman A. Kuranga, François L. Roger, Veronique Chevalier, Richard J. Webby, Patrick C. Y. Woo, Leo L. M. Poon, Malik Peiris

DOI: 10.1128/JVI.01236-19

 

ABSTRACT

Genetic recombination has frequently been observed in coronaviruses. Here, we sequenced multiple complete genomes of dromedary camel coronavirus HKU23 (DcCoV-HKU23) from Nigeria, Morocco and Ethiopia and identified several genomic positions indicative of cross species virus recombination events among other Betacoronaviruses of the subgenus Embecovirus (clade A β-CoVs). Recombinant fragments of a rabbit coronavirus (RbCoV-HKU14) were identified at the hemagglutinin esterase gene position. Homolog fragments of a rodent CoV were also observed at the 8.9 kDa open reading frame 4a at the 3′ end of the spike gene. The patterns of recombination varied geographically across the African region, highlighting a mosaic structure of DcCoV-HKU23 genomes circulating in dromedaries. Our results highlighted active recombination of coronaviruses circulating in dromedaries and is also relevant to the emergence and evolution of other Betacoronaviruses including MERS-coronavirus (MERS-CoV).

 

IMPORTANCE

Genetic recombination is often demonstrated in coronaviruses and can result in host range expansion or alteration in tissue tropism. Here, we showed interspecies recombination events of an endemic dromedary camel coronavirus HKU23 with other clade A Betacoronaviruses. Our results supported the possibility that the zoonotic pathogen, MERS-CoV, which also co-circulates in the same camel species, may have undergone similar recombination events facilitating its emergence or may do so in its future evolution.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Coronavirus; Betacoronavirus; Embecovirus; MERS-CoV; Camels; Africa Region; Recombination.

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A Case Study Evaluating the #Risk of #Infection from Middle Eastern Respiratory Syndrome #Coronavirus (#MERS-CoV) in a #Hospital Setting Through #Bioaerosols (Risk Anal., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Risk Anal. 2019 Sep 16. doi: 10.1111/risa.13389. [Epub ahead of print]

A Case Study Evaluating the Risk of Infection from Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) in a Hospital Setting Through Bioaerosols.

Adhikari U1, Chabrelie A1, Weir M2, Boehnke K3, McKenzie E4, Ikner L5, Wang M6, Wang Q7, Young K8, Haas CN9, Rose J8, Mitchell J1.

Author information: 1 Department of Biosystems and Agricultural Engineering, Michigan State University, East Lansing, MI, USA. 2 Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH, USA. 3 Department of Anesthesiology & the Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor, MI, USA. 4 Department of Civil and Environmental Engineering, Temple University, Philadelphia, PA, USA. 5 Department of Soil, Water and Environmental Science, University of Arizona, Tucson, AZ, USA. 6 Department of Civil & Environmental Engineering, University of South Florida, Tampa, FL, USA. 7 Department of Animal and Food Sciences, University of Delaware, Newark, DE, USA. 8 Department of Fisheries and Wildlife, Michigan State University, East Lansing, MI, USA. 9 Department of Civil, Architectural and Environmental Engineering, Drexel University, Philadelphia, PA, USA.

 

Abstract

Middle Eastern respiratory syndrome, an emerging viral infection with a global case fatality rate of 35.5%, caused major outbreaks first in 2012 and 2015, though new cases are continuously reported around the world. Transmission is believed to mainly occur in healthcare settings through aerosolized particles. This study uses Quantitative Microbial Risk Assessment to develop a generalizable model that can assist with interpreting reported outbreak data or predict risk of infection with or without the recommended strategies. The exposure scenario includes a single index patient emitting virus-containing aerosols into the air by coughing, leading to short- and long-range airborne exposures for other patients in the same room, nurses, healthcare workers, and family visitors. Aerosol transport modeling was coupled with Monte Carlo simulation to evaluate the risk of MERS illness for the exposed population. Results from a typical scenario show the daily mean risk of infection to be the highest for the nurses and healthcare workers (8.49 × 10-4 and 7.91 × 10-4 , respectively), and the lowest for family visitors and patients staying in the same room (3.12 × 10-4 and 1.29 × 10-4 , respectively). Sensitivity analysis indicates that more than 90% of the uncertainty in the risk characterization is due to the viral concentration in saliva. Assessment of risk interventions showed that respiratory masks were found to have a greater effect in reducing the risks for all the groups evaluated (>90% risk reduction), while increasing the air exchange was effective for the other patients in the same room only (up to 58% risk reduction).

© 2019 Society for Risk Analysis.

KEYWORDS: Hospital; MERS-CoV; QMRA; mitigation; risk characterization

PMID: 31524301 DOI: 10.1111/risa.13389

Keywords: MERS-CoV.

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#MERS #Coronavirus and the #OneHealth concept (PeerJ., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

PeerJ. 2019 Aug 22;7:e7556. doi: 10.7717/peerj.7556. eCollection 2019.

Middle East Respiratory Syndrome Coronavirus and the One Health concept.

Hemida MG1,2.

Author information: 1 Department of Microbiology and Parasitology, College of Veterinary Medicine, King Faisal University, Al-Hufuf, Al-Hasa, Saudi Arabia. 2 Department of Virology, faculty of veterinary medicine, Kafrelsheikh University, Egypt, Kafrelsheikh University, Kafrelsheikh, Kafrelsheikh, Egypt.

 

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is one of the major threats to the healthcare systems in some countries, especially in the Arabian Peninsula. MERS-CoV is considered an ideal example of the One Health concept. This is due to the animals, especially dromedary camels, play important roles in the transmission and sustainability of the virus, and the virus can be transmitted through aerosols of infected patients into the environment. However, there is some debate regarding the origin of MERS-CoV either from bats or other unknown reservoirs. The dromedary camel is the only identified animal reservoir to date. These animals play important roles in sustaining the virus in certain communities and may act as an amplifier of the virus by secreting it in their body fluids, especially in nasal and rectal discharges. MERS-CoV has been detected in the nasal and rectal secretions of infected camels, and MERS-CoV of this origin has full capacity to infect human airway epithelium in both in vitro and in vivo models. Other evidence confirms the direct transmission of MERS-CoV from camels to humans, though the role of camel meat and milk products has yet to be well studied. Human-to-human transmission is well documented through contact with an active infected patient or some silently infected persons. Furthermore, there are some significant risk factors of individuals in close contact with a positive MERS-CoV patient, including sleeping in the same patient room, removing patient waste (urine, stool, and sputum), and touching respiratory secretions from the index case. Outbreaks within family clusters have been reported, whereby some blood relative patients were infected through their wives in the same house were not infected. Some predisposing genetic factors favor MERS-CoV infection in some patients, which is worth investigating in the near future. The presence of other comorbidities may be another factor. Overall, there are many unknown/confirmed aspects of the virus/human/animal network. Here, the most recent advances in this context are discussed, and the possible reasons behind the emergence and sustainability of MERS-CoV in certain regions are presented. Identification of the exact mechanism of transmission of MERS-CoV from camels to humans and searching for new reservoir/s are of high priority. This will reduce the shedding of the virus into the environment, and thus the risk of human infection can be mitigated.

KEYWORDS: Dromedary camel; Human; MERS-CoV; One Health concept; Reservoir; Transmision; Zoonosis

PMID: 31497405 PMCID: PMC6708572 DOI: 10.7717/peerj.7556

Keywords: MERS-CoV; Human; Camels.

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A #Fusion #Peptide in the #Spike Protein of #MERS #Coronavirus (Viruses, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Viruses. 2019 Sep 5;11(9). pii: E825. doi: 10.3390/v11090825.

A Fusion Peptide in the Spike Protein of MERS Coronavirus.

Alsaadi EAJ1, Neuman BW2, Jones IM3.

Author information: 1 School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK. 2 Biology Department, CASE, Texas A&M University, Texarkana, TX 75503, USA. 3 School of Biological Sciences, University of Reading, Reading RG6 6AJ, UK. i.m.jones@rdg.ac.uk.

 

Abstract

Coronaviruses represent current and emerging threats for many species, including humans. Middle East respiratory syndrome-related coronavirus (MERS-CoV) is responsible for sporadic infections in mostly Middle Eastern countries, with occasional transfer elsewhere. A key step in the MERS-CoV replication cycle is the fusion of the virus and host cell membranes mediated by the virus spike protein, S. The location of the fusion peptide within the MERS S protein has not been precisely mapped. We used isolated peptides and giant unilamellar vesicles (GUV) to demonstrate membrane binding for a peptide located near the N-terminus of the S2 domain. Key residues required for activity were mapped by amino acid replacement and their relevance in vitro tested by their introduction into recombinant MERS S protein expressed in mammalian cells. Mutations preventing membrane binding in vitro also abolished S-mediated syncytium formation consistent with the identified peptide acting as the fusion peptide for the S protein of MERS-CoV.

KEYWORDS: MERS; coronavirus; fusion assay; membrane; peptide; spike protein

PMID: 31491938 DOI: 10.3390/v11090825

Keywords: MERS-CoV.

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A Novel #Bacterium-Like Particle #Vaccine Displaying the #MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice (Viruses, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Viruses. 2019 Aug 29;11(9). pii: E799. doi: 10.3390/v11090799.

A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice.

Li E1,2, Chi H3,4, Huang P2,5, Yan F2, Zhang Y2,6, Liu C2,5, Wang Z2,5, Li G2,7, Zhang S2,6, Mo R2,5, Jin H2,8, Wang H2,8, Feng N2,9, Wang J5, Bi Y10, Wang T2,9, Sun W2,9, Gao Y2,9, Zhao Y11,12, Yang S13,14, Xia X15,16.

Author information: 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. 2 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. 3 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. ch_amms@163.com. 4 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China. ch_amms@163.com. 5 Animal Science and Technology College, Jilin Agricultural University, Changchun 130118, China. 6 College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China. 7 College of Animal Science and Technology, Shihezi University, Shihezi 832003, China. 8 College of Veterinary Medicine, Jilin University, Changchun 130062, China. 9 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China. 10 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. 11 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. zhaoyongkun1976@126.com. 12 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China. zhaoyongkun1976@126.com.  13 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. yst62041@163.com. 14 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China. yst62041@163.com. 15 Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130000, China. xiaxzh@cae.cn. 16 Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130000, China. xiaxzh@cae.cn.

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV), a new coronavirus that has been causing severe and fatal acute respiratory illnesses in humans since its outbreak in 2012, has raised public fear worldwide. The development of prophylactics and therapeutics is urgently needed to prevent and control MERS-CoV infections. In this study, a bacterium (Lactococcus lactis)-like particle (BLP) vaccine displaying the MERS-CoV receptor-binding domain (RBD) was developed, and gram-positive enhancer matrix (GEM) particles were used as substrates to externally bind to the MERS-CoV RBD through a protein anchor (PA). The designs included different numbers of lysin motif (LysM) repeats in the PAs linked by linkers (RBD-linker-PA2 (RLP2), RBD-linker-PA3 (RLP3) and RBD-PA3 (RP3)), and three LysM repeats and a linker in the fusion proteins increased the binding activity to the RBD. The specific immune responses were tested by intranasally immunizing mice with RLP3-GEM with or without the adjuvant GEL01. The results showed that GEL01-adjuvanted RLP3-GEM increased the systemic humoral, cellular and local mucosal immune responses in the mouse model, especially in the intestinal tract. The above results indicate that the MERS-CoV BLP product has the potential to be developed into a promising mucosal candidate vaccine to protect against MERS-CoV infections.

KEYWORDS: MERS-CoV; bacterium-like particles; intranasal administration; mucosal immune; subunit vaccine

PMID: 31470645 DOI: 10.3390/v11090799

Keywords: MERS-CoV; Vaccines; Animal models.

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#Economic #Impact of the 2015 #MERS #Outbreak on the Republic of #Korea’s #Tourism-Related #Industries (Health Secur., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Health Secur. 2019 Mar/Apr;17(2):100-108. doi: 10.1089/hs.2018.0115. Epub 2019 Apr 10.

Economic Impact of the 2015 MERS Outbreak on the Republic of Korea’s Tourism-Related Industries.

Joo H1, Maskery BA2, Berro AD3, Rotz LD4, Lee YK5, Brown CM6.

Author information: 1 Heesoo Joo, PhD, is an Economist, Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, Georgia. 2 Brian A. Maskery, PhD, is an Economist, Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, Georgia. 3 Andre D. Berro, MPH, is a Public Health Advisor, Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, Georgia. 4 Lisa D. Rotz, MD, is a Medical Epidemiologist, Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, Georgia. 5 Yeon-Kyeng Lee, PhD, is Division Director, Korea Centers for Disease Control and Prevention, Cheongju-si, Chungcheongbuk-do, Republic of Korea. 6 Clive M. Brown, MD, is Branch Chief, Quarantine and Border Health Services, Division of Global Migration and Quarantine, Centers for Disease Control and Prevention, Atlanta, Georgia.

 

Abstract

The 2015 Middle East respiratory syndrome (MERS) outbreak in the Republic of Korea (ROK) is an example of an infectious disease outbreak initiated by international travelers to a high-income country. This study was conducted to determine the economic impact of the MERS outbreak on the tourism and travel-related service sectors, including accommodation, food and beverage, and transportation, in the ROK. We projected monthly numbers of noncitizen arrivals and indices of services for 3 travel-related service sectors during and after the MERS outbreak (June 2015 to June 2016) using seasonal autoregressive integrated moving average models. Tourism losses were estimated by multiplying the monthly differences between projected and actual numbers of noncitizen arrivals by average tourism expenditure per capita. Estimated tourism losses were allocated to travel-related service sectors to understand the distribution of losses across service sectors. The MERS outbreak was correlated with a reduction of 2.1 million noncitizen visitors corresponding with US$2.6 billion in tourism loss for the ROK. Estimated losses in the accommodation, food and beverage service, and transportation sectors associated with the decrease of noncitizen visitors were US$542 million, US$359 million, and US$106 million, respectively. The losses were demonstrated by lower than expected indices of services for the accommodation and food and beverage service sectors in June and July 2015 and for the transportation sector in June 2015. The results support previous findings that public health emergencies due to traveler-associated outbreaks of infectious diseases can cause significant losses to the broader economies of affected countries.

KEYWORDS: Economic burden of disease; Economic impact; Middle East respiratory syndrome; Outbreak; Tourism; Travel industry

PMID: 30969152 PMCID: PMC6560634 [Available on 2020-04-10] DOI: 10.1089/hs.2018.0115 [Indexed for MEDLINE]

Keywords: MERS-CoV; South Korea; Society.

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