Genomic Characterization of a Newly Discovered Coronavirus Associated with Acute Respiratory Distress Syndrome in Humans

By S. V. Boheemen, M. Graaf, C. Lauber, T. Bestebroer, V. S. Raj, A. Zaki, A. Osterhaus, B. Haagmans, Alexander E. Gorbalenya, E. Snijder and 1 more. mBio, 2012

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ABSTRACT A novel human coronavirus (HCoV-EMC/2012) was isolated from a man with acute pneumonia and renal failure in June 2012. This report describes the complete genome sequence, genome organization, and expression strategy of HCoV-EMC/2012 and its relation with known coronaviruses. The genome contains 30,119 nucleotides and contains at least 10 predicted open reading frames, 9 of which are predicted to be expressed from a nested set of seven subgenomic mRNAs. Phylogenetic analysis of the replicase gene of coronaviruses with completely sequenced genomes showed that HCoV-EMC/2012 is most closely related to Tylonycteris bat coronavirus HKU4 (BtCoV-HKU4) and Pipistrellus bat coronavirus HKU5 (BtCoV-HKU5), which prototype two species in lineage C of the genus Betacoronavirus. In accordance with the guidelines of the International Committee on Taxonomy of Viruses, and in view of the 75% and 77% amino acid sequence identity in 7 conserved replicase domains with BtCoV-HKU4 and BtCoV-HKU5, respectively, we propose that HCoV-EMC/2012 prototypes a novel species in the genus Betacoronavirus. HCoV-EMC/2012 may be most closely related to a coronavirus detected in Pipistrellus pipistrellus in The Netherlands, but because only a short sequence from the most conserved part of the RNA-dependent RNA polymerase-encoding region of the genome was reported for this bat virus, its genetic distance from HCoV-EMC remains uncertain. HCoV-EMC/2012 is the sixth coronavirus known to infect humans and the first human virus within betacoronavirus lineage C. IMPORTANCE Coronaviruses are capable of infecting humans and many animal species. Most infections caused by human coronaviruses are relatively mild. However, the outbreak of severe acute respiratory syndrome (SARS) caused by SARS-CoV in 2002 to 2003 and the fatal infection of a human by HCoV-EMC/2012 in 2012 show that coronaviruses are able to cause severe, sometimes fatal disease in humans. We have determined the complete genome of HCoV-EMC/2012 using an unbiased virus discovery approach involving next-generation sequencing techniques, which enabled subsequent state-of-the-art bioinformatics, phylogenetics, and taxonomic analyses. By establishing its complete genome sequence, HCoV-EMC/2012 was characterized as a new genotype which is closely related to bat coronaviruses that are distant from SARS-CoV. We expect that this information will be vital to rapid advancement of both clinical and vital research on this emerging pathogen. Coronaviruses are capable of infecting humans and many animal species. Most infections caused by human coronaviruses are relatively mild. However, the outbreak of severe acute respiratory syndrome (SARS) caused by SARS-CoV in 2002 to 2003 and the fatal infection of a human by HCoV-EMC/2012 in 2012 show that coronaviruses are able to cause severe, sometimes fatal disease in humans. We have determined the complete genome of HCoV-EMC/2012 using an unbiased virus discovery approach involving next-generation sequencing techniques, which enabled subsequent state-of-the-art bioinformatics, phylogenetics, and taxonomic analyses. By establishing its complete genome sequence, HCoV-EMC/2012 was characterized as a new genotype which is closely related to bat coronaviruses that are distant from SARS-CoV. We expect that this information will be vital to rapid advancement of both clinical and vital research on this emerging pathogen.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/98513efd2f4e86626a263f1eb350ed2702ecb8ec

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Citations in the corpus

Middle East Respiratory Syndrome Coronavirus: Another Zoonotic Betacoronavirus Causing SARS-Like Disease (2015, background): “Among them, the MERS-CoV accessory protein 4a, a double-stranded RNA (dsRNA)-binding protein, exhibits potent antagonistic activity at multiple levels of the interferon response, including the prevention of interferon beta synthesis through the inhibition of interferon promoter activation and interf”
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Screening of an FDA-Approved Compound Library Identifies Four Small-Molecule Inhibitors of Middle East Respiratory Syndrome Coronavirus Replication in Cell Culture (2014, background): “MERS-CoV was identified as a member of lineage C of the genus 82 Betacoronavirus (2), which also includes coronaviruses of bat (13, 14) and hedgehog origin (6).”
Coronaviruses: An Overview of Their Replication and Pathogenesis (2015, background): “MERS-CoV is a group 2c β-coronavirus highly related to two previously identifi ed bat coronaviruses, HKU4 and HKU5 [ 95 ].”
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Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4 (2013, background): “Genetic and phy-logenetic characterization has shown that MERS-CoV belongs to lineage C of the genus of betacoronavirus and is closely related to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5, although the direct source and reservoirs of MERS-CoV remain uncertain [2, 7, 8] ”
Accessory proteins of SARS-CoV and other coronaviruses (2014, background): “MERS coronavirus also contains an internal ORF within the nucleocapsid gene, which has not yet been characterized (van Boheemen et al., 2012).”
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