Genetic Characterization of Betacoronavirus Lineage C Viruses in Bats Reveals Marked Sequence Divergence in the Spike Protein of Pipistrellus Bat Coronavirus HKU5 in Japanese Pipistrelle: Implications for the Origin of the Novel Middle East Respiratory Syndrome Coronavirus

Lau, Susanna K.P.; Li, Kenneth S. M.; Tsang, Alan K.L.; Lam, Carol S. F.; Ahmed, Shakil; Chen, Honglin; Chan, Kwok-Hung; Woo, Patrick C. Y.; Yuen, Kwok‐Yung

doi:10.1128/jvi.01055-13

Cited by 254 publications

(272 citation statements)

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“…In the last 2 years, studies have shown that dromedaries are the hosts of at least two distinct coronaviruses. MERS-CoV is a lineage C betacoronavirus closely related to bat coronaviruses discovered by us (Lau et al, 2013b;Memish et al, 2013;Yang et al, 2014), whereas DcCoV UAE-HKU23 is a lineage A betacoronavirus closely related to other members of the species Betacoronavirus 1 found in humans and at least 15 other mammalian species (Woo et al, 2014b). Serological studies have shown that minimal cross-reactivity exists between MERS-CoV and DcCoV UAE-HKU23 (Woo et al, 2014b).…”

Section: Discussionmentioning

confidence: 99%

A novel dromedary camel enterovirus in the family Picornaviridae from dromedaries in the Middle East

Woo

Lau

et al. 2015

Journal of General Virology

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The recent emergence of Middle East respiratory syndrome coronavirus from the Middle East and the discovery of the virus from dromedary camels have boosted interest in the search for novel viruses in dromedaries. Whilst picornaviruses are known to infect various animals, their existence in dromedaries was unknown. We describe the discovery of a novel picornavirus, dromedary camel enterovirus (DcEV), from dromedaries in Dubai. Among 215 dromedaries, DcEV was detected in faecal samples of four (1.9 %) dromedaries [one (0.5 %) adult dromedary and three (25 %) dromedary calves] by reverse transcription PCR. Analysis of two DcEV genomes showed that DcEV was clustered with other species of the genus Enterovirus and was most closely related to and possessed highest amino acid identities to the species Enterovirus E and Enterovirus F found in cattle. The G+C content of DcEV was 45 mol%, which differed from that of Enterovirus E and Enterovirus F (49-50 mol%) by 4-5 %. Similar to other members of the genus Enterovirus, the 59 UTR of DcEV possessed a putative type I internal ribosome entry site. The low ratios of the number of nonsynonymous substitutions per non-synonymous site to the number of synonymous substitutions per synonymous site (K a /K s ) of various coding regions suggested that dromedaries are the natural reservoir in which DcEV has been stably evolving. These results suggest that DcEV is a novel species of the genus Enterovirus in the family Picornaviridae. Western blot analysis using recombinant DcEV VP1 polypeptide showed a high seroprevalence of 52 % among serum samples from 172 dromedaries for IgG, concurring with its much higher infection rates in dromedary calves than in adults. Further studies are important to understand the pathogenicity, epidemiology and genetic evolution of DcEV in this unique group of animals.

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Section: Discussionmentioning

confidence: 99%

A novel dromedary camel enterovirus in the family Picornaviridae from dromedaries in the Middle East

Woo

Lau

et al. 2015

Journal of General Virology

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“…The lineage C betacoronaviruses Pipistrellus bat coronavirus HKU5 and Tylonycteris bat coronavirus HKU4 are genetically related to MERS-CoV and likely all emerged from a distant common ancestor centuries ago. 39 Lineage C betacoronaviruses identified in European and African Pipistrellus and Nycteris bats were determined to be genetically similar and phylogenetically related to MERSCoV. 7 Additionally, in Bisha, Saudi Arabia, a few months after the first human case of MERS-CoV infection was documented, a 190-nucleotide fragment of a coronavirus RNA-dependent RNA polymerase gene was amplified from bat feces and shared 100% sequence identity with the original MERS-CoV isolate from the same geographic region.…”

Section: Human Mers-cov Infectionsmentioning

confidence: 99%

A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection

2016

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Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a Saudi Arabian man with fatal pneumonia. Since the original case in 2012, MERS-CoV infections have been reported in >1500 humans, and the case fatality rate is currently 35%. This lineage C betacoronavirus has been reported to cause a wide range of disease severity in humans, ranging from asymptomatic to progressive fatal pneumonia that may be accompanied by renal or multiorgan failure. Although the clinical presentation of human MERS-CoV infection has been documented, many facets of this emerging disease are still unknown and could be studied with animal models. Several animal models of MERS-CoV have been developed, including New Zealand white rabbits, transduced or transgenic mice that express human dipeptidyl peptidase 4, rhesus macaques, and common marmosets. This review provides an overview of the current state of knowledge on human MERS-CoV infections, the probable origin of MERS-CoV, and the available animal models of MERS-CoV infection. Evaluation of the benefits and limitations of these models will aid in appropriate model selection for studying viral pathogenesis and transmission, as well as for testing vaccines and antivirals against MERS-CoV.Keywords animal models, common marmosets, dipeptidyl peptidase 4, mice, Middle East respiratory syndrome coronavirus, pathogenicity, rabbits, respiratory system, review, rhesus macaques, transgenic Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated from a man in Saudi Arabia in 2012, and MERS-CoV infections have now been reported in >20 countries. 76,79 Originally called human coronavirus-EMC/2012, the virus was renamed MERS-CoV by the International Committee on Taxonomy of Viruses. 20,67 In humans, MERS-CoV is 1 of 6 coronaviruses that cause respiratory disease; however, it is currently the only known pathogenic human lineage C betacoronavirus. 31,68 MERS-CoV infections in humans range from asymptomatic to progressive fatal pneumonia with occasional renal or multiorgan failure. 44,52 To date, published autopsy data from fatal human cases are not available, and the exact route of viral transmission to and among humans is unknown. Additionally, there are currently no approved MERS-CoV-specific countermeasures. Thus, development of animal models to study the pathology and pathogenesis of MERS-CoV, the routes of viral transmission, and the efficacy of treatments and vaccines is critical. Here, we review the current state of knowledge on MERS-CoV infections in humans and potential animal reservoirs for the virus and provide an overview and analysis of animal models of MERS-CoV infection.

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“…To date, MERS-CoV has infected at least 77 people and was able to be transmitted from human to human. The genomic sequence of MERS-CoV is closely related to the sequences of certain bat coronaviruses (3)(4)(5), raising concerns over persistent bat-to-human cross-species transmission of the virus. The clinical signs and epidemic patterns of MERS-CoV are reminiscent of the severe acute respiratory syndrome coronavirus (SARS-CoV), the etiological agent of the worldwide SARS epidemic in 2002-2003 that infected more than 8,000 people with a ϳ10% fatality rate (6,7).…”

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confidence: 99%

Crystal Structure of the Receptor-Binding Domain from Newly Emerged Middle East Respiratory Syndrome Coronavirus

Chen

Rajashankar

Yang

et al. 2013

J Virol

118

123

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The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 77 people, with a fatality rate of more than 50%. Alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. Here we have identified the receptor-binding domain (RBD) from the MERS-CoV spike protein and determined its crystal structure. This study also presents a structural comparison of MERS-CoV RBD with other coronavirus RBDs, successfully positioning MERS-CoV on the landscape of coronavirus evolution and providing insights into receptor binding by MERS-CoV. Furthermore, we found that MERS-CoV RBD functions as an effective entry inhibitor of MERS-CoV. The identified MERS-CoV RBD may also serve as a potential candidate for MERS-CoV subunit vaccines. Overall, this study enhances our understanding of the evolution of coronavirus RBDs, provides insights into receptor recognition by MERS-CoV, and may help control the transmission of MERS-CoV in humans. Since the summer of 2012, a novel coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged from the Middle East and spread to parts of Europe. MERS-CoV infection often leads to acute pneumonia and renal failure, and the human fatality rate is more than 50% (1, 2). To date, MERS-CoV has infected at least 77 people and was able to be transmitted from human to human. The genomic sequence of MERS-CoV is closely related to the sequences of certain bat coronaviruses (3-5), raising concerns over persistent bat-to-human cross-species transmission of the virus. The clinical signs and epidemic patterns of MERS-CoV are reminiscent of the severe acute respiratory syndrome coronavirus (SARS-CoV), the etiological agent of the worldwide SARS epidemic in 2002-2003 that infected more than 8,000 people with a ϳ10% fatality rate (6, 7). MERS-CoV poses a significant threat to global health and economy.Coronaviruses are enveloped and positive-stranded RNA viruses and can be divided into three major genera, ␣, ␤, and ␥ (8). They mainly cause respiratory, gastrointestinal, and central nervous system diseases in mammals and birds. Coronaviruses recognize a variety of host receptors. Human NL63 respiratory coronavirus (HCoV-NL63) from ␣-genus and SARS-CoV from ␤-genus both recognize angiotensin-converting enzyme 2 (ACE2) as their host receptor (9, 10). Porcine respiratory coronavirus (PRCV) and some other coronaviruses from ␣-genus recognize aminopeptidase N (APN) (11, 12). Mouse hepatitis coronavirus (MHV) from ␤-genus recognizes carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) (13, 14), although certain MHV strains also recognize heparan sulfate (15, 16). Some coronaviruses from each of the three genera recognize sugars (17-20). MERS-CoV belongs to the ␤-genus and uses human dipeptidyl peptidase 4 (DPP4) as its host receptor (21). Receptor recognition is a major determinant of coronavirus host range and tropism.An envelope-anchored trimeric spike p...

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Genetic Characterization of Betacoronavirus Lineage C Viruses in Bats Reveals Marked Sequence Divergence in the Spike Protein of Pipistrellus Bat Coronavirus HKU5 in Japanese Pipistrelle: Implications for the Origin of the Novel Middle East Respiratory Syndrome Coronavirus

Abstract: While the novel Middle East respiratory syndrome coronavirus (MERS-CoV) is closely related to

Cited by 254 publications

References 88 publications

A novel dromedary camel enterovirus in the family Picornaviridae from dromedaries in the Middle East

A novel dromedary camel enterovirus in the family Picornaviridae from dromedaries in the Middle East

A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection

Crystal Structure of the Receptor-Binding Domain from Newly Emerged Middle East Respiratory Syndrome Coronavirus

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