Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study
Chantal B.E.M. Reusken, Bart L. Haagmans1, Marcel A. Müller2, Carlos Gutierrez3, Gert Jan Godeke, Benjamin Meyer2, Doreen Muth2, V. Stalin Raj1, Laura Smits De Vries4, Victor M. Corman2, Jan Felix Drexler2, Saskia L. Smits1, Yasmin El Tahir5, Rita de Sousa6, Janko van Beek, Norbert Nowotny7, Norbert Nowotny5, Kees van Maanen, Ezequiel Hidalgo-Hermoso, Berend Jan Bosch4, Peter J. M. Rottier4, Albert D. M. E. Osterhaus1, Christian Gortázar-Schmidt8, Christian Drosten2, Marion Koopmans1 •
TL;DR: Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection of camel populations, and possible animal reservoirs of MERS-CoV are investigated by assessing specific serum antibodies in livestock.
Abstract: Summary Background A new betacoronavirus—Middle East respiratory syndrome coronavirus (MERS-CoV)—has been identified in patients with severe acute respiratory infection. Although related viruses infect bats, molecular clock analyses have been unable to identify direct ancestors of MERS-CoV. Anecdotal exposure histories suggest that patients had been in contact with dromedary camels or goats. We investigated possible animal reservoirs of MERS-CoV by assessing specific serum antibodies in livestock. Methods We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. Results were confirmed by virus neutralisation tests for MERS-CoV and bovine coronavirus. Findings 50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies. Interpretation MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection. Funding European Union, European Centre For Disease Prevention and Control, Deutsche Forschungsgemeinschaft.
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TL;DR: The viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome are explored and the diversity and potential of bat-borne coronaviruses are highlighted.
Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs. Coronaviruses have a broad host range and distribution, and some highly pathogenic lineages have spilled over to humans and animals. Here, Cui, Li and Shi explore the viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome.
3,970 citations
TL;DR: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronav virus into the human population in the twenty-first century, and the current state of development of measures to combat emerging coronaviruses is discussed.
Abstract: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses.
2,794 citations
Shuo Su1, Gary Wong2, Weifeng Shi, Jun Liu3, Jun Liu2, Alexander Lai4, Jiyong Zhou1, Wenjun Liu2, Yuhai Bi2, George F. Gao •
TL;DR: This review aims to compare and contrast the different HCoVs with regard to epidemiology and pathogenesis, in addition to the virus evolution and recombination events which have, on occasion, resulted in outbreaks amongst humans.
2,268 citations
Cites background from "Middle East respiratory syndrome co..."
...In the case of MERS-CoV, studies in Oman, Saudi Arabia, Qatar, United Arab Emirates, and Jordan have shown that dromedary camels are seropositive for neutralizing antibodies against MERS-CoV [54], as well as camels of Middle East origin in Africa, including Egypt, Kenya, Nigeria, Ethiopia, Tunisia, Somalia, and Sudan [55]....
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Canrong Wu1, Yang Liu2, Yueying Yang2, Peng Zhang2, Wu Zhong, Yali Wang2, Qiqi Wang2, Yang Xu2, Mingxue Li2, Xing-Zhou Li, Mengzhu Zheng1, Lixia Chen2, Hua Li2, Hua Li1 •
TL;DR: This study systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling and constructed a database of 78 commonly used anti-viral drugs.
1,680 citations
TL;DR: The epidemiology, virology, clinical features and current treatment strategies of SARS and MERS are summarized, and the discovery and development of new virus-based and host-based therapeutic options for CoV infections are discussed.
Abstract: Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which are caused by coronaviruses, have attracted substantial attention owing to their high mortality rates and potential to cause epidemics. Yuen and colleagues discuss progress with treatment options for these syndromes, including virus- and host-targeted drugs, and the challenges that need to be overcome in their further development. In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections.
1,388 citations
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V. Stalin Raj1, Huihui Mou2, Saskia L. Smits1, Dick H. W. Dekkers1, Marcel A. Müller3, Ronald Dijkman4, Doreen Muth3, Jeroen Demmers1, Ali Moh Zaki, Ron A. M. Fouchier1, Volker Thiel5, Volker Thiel4, Christian Drosten3, Peter J. M. Rottier2, Albert D. M. E. Osterhaus1, Berend Jan Bosch2, Bart L. Haagmans1 •
TL;DR: Dipeptidyl peptidase 4 (DPP4; also known as CD26) is identified as a functional receptor for hCoV-EMC and will contribute critically to the understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.
Abstract: Most human coronaviruses cause mild upper respiratory tract disease but may be associated with more severe pulmonary disease in immunocompromised individuals. However, SARS coronavirus caused severe lower respiratory disease with nearly 10% mortality and evidence of systemic spread. Recently, another coronavirus (human coronavirus-Erasmus Medical Center (hCoV-EMC)) was identified in patients with severe and sometimes lethal lower respiratory tract infection. Viral genome analysis revealed close relatedness to coronaviruses found in bats. Here we identify dipeptidyl peptidase 4 (DPP4; also known as CD26) as a functional receptor for hCoV-EMC. DPP4 specifically co-purified with the receptor-binding S1 domain of the hCoV-EMC spike protein from lysates of susceptible Huh-7 cells. Antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells and Huh-7 cells. Expression of human and bat (Pipistrellus pipistrellus) DPP4 in non-susceptible COS-7 cells enabled infection by hCoV-EMC. The use of the evolutionarily conserved DPP4 protein from different species as a functional receptor provides clues about the host range potential of hCoV-EMC. In addition, it will contribute critically to our understanding of the pathogenesis and epidemiology of this emerging human coronavirus, and may facilitate the development of intervention strategies.
1,743 citations
TL;DR: In a surveillance study for CoV in noncaged animals from the wild areas of the Hong Kong Special Administration Region, a CoV closely related to SARS-CoV is identified from 23 (39%) of 59 anal swabs of wild Chinese horseshoe bats by using RT-PCR and the presence of a 29-bp insertion in ORF 8 of bat-SARS- coV genome suggests that it has a common ancestor with civet SARS -CoV.
Abstract: Although the finding of severe acute respiratory syndrome coronavirus (SARS-CoV) in caged palm civets from live animal markets in China has provided evidence for interspecies transmission in the genesis of the SARS epidemic, subsequent studies suggested that the civet may have served only as an amplification host for SARS-CoV. In a surveillance study for CoV in noncaged animals from the wild areas of the Hong Kong Special Administration Region, we identified a CoV closely related to SARS-CoV (bat-SARS-CoV) from 23 (39%) of 59 anal swabs of wild Chinese horseshoe bats (Rhinolophus sinicus) by using RT-PCR. Sequencing and analysis of three bat-SARS-CoV genomes from samples collected at different dates showed that bat-SARS-CoV is closely related to SARS-CoV from humans and civets. Phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b CoV, distantly related to known group 2 CoV. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike genes, ORF 3 and ORF 8, which are the regions where most variations also were observed between human and civet SARS-CoV genomes. In addition, the presence of a 29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats by using an enzyme immunoassay. Neutralizing antibody to human SARS-CoV also was detected in bats with lower viral loads. Precautions should be exercised in the handling of these animals.
1,419 citations
Abdullah M. Assiri, Allison McGeer1, Trish M. Perl2, Connie S. Price3, Abdullah A. Al Rabeeah, Derek A. T. Cummings2, Zaki N. Alabdullatif, Maher Assad, Abdulmohsen Almulhim, Hatem Q. Makhdoom, Hossam Madani, Rafat F. Alhakeem, Jaffar A. Al-Tawfiq2, Matthew Cotten4, Simon J. Watson4, Paul Kellam5, Paul Kellam4, Alimuddin Zumla6, Alimuddin Zumla5, Ziad A. Memish7 •
TL;DR: Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity and surveillance and infection-control measures are critical to a global public health response.
Abstract: Background In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care–acquired MERS-CoV infections. Methods Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. Results Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained ...
1,115 citations
TL;DR: A probabilistic model is introduced that describes the worldwide spread of infectious diseases and shows that a forecast of the geographical spread of epidemics is indeed possible, taking into account national and international civil aviation traffic.
Abstract: The rapid worldwide spread of severe acute respiratory syndrome demonstrated the potential threat an infectious disease poses in a closely interconnected and interdependent world. Here we introduce a probabilistic model that describes the worldwide spread of infectious diseases and demonstrate that a forecast of the geographical spread of epidemics is indeed possible. This model combines a stochastic local infection dynamics among individuals with stochastic transport in a worldwide network, taking into account national and international civil aviation traffic. Our simulations of the severe acute respiratory syndrome outbreak are in surprisingly good agreement with published case reports. We show that the high degree of predictability is caused by the strong heterogeneity of the network. Our model can be used to predict the worldwide spread of future infectious diseases and to identify endangered regions in advance. The performance of different control strategies is analyzed, and our simulations show that a quick and focused reaction is essential to inhibiting the global spread of epidemics.
1,075 citations
TL;DR: Coronaviruses possess the largest genomes among all known RNA viruses, with G + C contents varying from 32% to 43%.
Abstract: The drastic increase in the number of coronaviruses discovered and coronavirus genomes being sequenced have given us an unprecedented opportunity to perform genomics and bioinformatics analysis on this family of viruses. Coronaviruses possess the largest genomes (26.4 to 31.7 kb) among all known RNA viruses, with G + C contents varying from 32% to 43%. Variable numbers of small ORFs are present between the various conserved genes (ORF1ab, spike, envelope, membrane and nucleocapsid) and downstream to nucleocapsid gene in different coronavirus lineages. Phylogenetically, three genera, Alphacoronavirus, Betacoronavirus and Gammacoronavirus, with Betacoronavirus consisting of subgroups A, B, C and D, exist. A fourth genus, Deltacoronavirus, which includes bulbul coronavirus HKU11, thrush coronavirus HKU12 and munia coronavirus HKU13, is emerging. Molecular clock analysis using various gene loci revealed that the time of most recent common ancestor of human/civet SARS related coronavirus to be 1999-2002, with estimated substitution rate of 410 -4 to 210 -2 substitutions per site per year. Recombination in coronaviruses was most notable between different strains of murine hepatitis virus (MHV), between different strains of infectious bronchitis virus, between MHV and bovine coronavirus, between feline coronavirus (FCoV) type I and canine coronavirus generating FCoV type II, and between the three genotypes of human
679 citations
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