title: 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 Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) and Pipistrellus bat CoV HKU5 (Pi-BatCoV HKU5) in bats from Hong Kong, and other potential lineage C betacoronaviruses in bats from Africa, Europe, and America, its animal origin remains obscure. To better understand the role of bats in its origin, we examined the molecular epidemiology and evolution of lineage C betacoronaviruses among bats. Ty-BatCoV HKU4 and Pi-BatCoV HKU5 were detected in 29% and 25% of alimentary samples from lesser bamboo bat (Tylonycteris pachypus) and Japanese pipistrelle (Pipistrellus abramus), respectively. Sequencing of their RNA polymerase (RdRp), spike (S), and nucleocapsid (N) genes revealed that MERS-CoV is more closely related to Pi-BatCoV HKU5 in RdRp (92.1% to 92.3% amino acid [aa] identity) but is more closely related to Ty-BatCoV HKU4 in S (66.8% to 67.4% aa identity) and N (71.9% to 72.3% aa identity). Although both viruses were under purifying selection, the S of Pi-BatCoV HKU5 displayed marked sequence polymorphisms and more positively selected sites than that of Ty-BatCoV HKU4, suggesting that Pi-BatCoV HKU5 may generate variants to occupy new ecological niches along with its host in diverse habitats. Molecular clock analysis showed that they diverged from a common ancestor with MERS-CoV at least several centuries ago. Although MERS-CoV may have diverged from potential lineage C betacoronaviruses in European bats more recently, these bat viruses were unlikely to be the direct ancestor of MERS-CoV. Intensive surveillance for lineage C betaCoVs in Pipistrellus and related bats with diverse habitats and other animals in the Middle East may fill the evolutionary gap.
authors.affiliation: State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
authors.forename: Susanna K P
authors.initials: SK
authors.lastname: Lau
authors.forename: Kenneth S M
authors.initials: KS
authors.lastname: Li
authors.forename: Alan K L
authors.initials: AK
authors.lastname: Tsang
authors.forename: Carol S F
authors.initials: CS
authors.lastname: Lam
authors.forename: Shakeel
authors.initials: S
authors.lastname: Ahmed
authors.forename: Honglin
authors.initials: H
authors.lastname: Chen
authors.forename: Kwok-Hung
authors.initials: KH
authors.lastname: Chan
authors.forename: Patrick C Y
authors.initials: PC
authors.lastname: Woo
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
mesh_terms: D000818:Animals; D002685:Chiroptera / Q000821:virology*; D016000:Cluster Analysis; D003332:Coronaviridae / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D018352:Coronavirus Infections / Q000662:veterinary* / Q000821:virology; D019143:Evolution, Molecular; D008562:Membrane Glycoproteins / Q000235:genetics*; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins / Q000235:genetics; D010802:Phylogeny; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D019590:Nucleocapsid Proteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D012324:RNA-Dependent RNA Polymerase