Genetic relatedness of the novel human group C betacoronavirus to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5

Abstract

The recent outbreak of severe respiratory infections associated with a novel group C betacoronavirus (HCoV-EMC) from Saudi Arabia has drawn global attention to another highly probable "SARS-like" animal-to-human interspecies jumping event in coronavirus (CoV). The genome of HCoV-EMC is most closely related to Tylonycteris bat coronavirus HKU4 (Ty-BatCoV HKU4) and Pipistrellus bat coronavirus HKU5 (Pi-BatCoV HKU5) we discovered in 2006. Phylogenetically, HCoV-EMC is clustered with Ty-BatCoV HKU4/Pi-BatCoV HKU5 with high bootstrap supports, indicating that HCoV-EMC is a group C betaCoV. The major difference between HCoV-EMC and Ty-BatCoV HKU4/Pi-BatCoV HKU5 is in the region between S and E, where HCoV-EMC possesses five ORFs (NS3a-NS3e) instead of four, with low (31%-62%) amino acid identities to Ty-BatCoV HKU4/Pi-BatCoV HKU5. Comparison of the seven conserved replicase domains for species demarcation shows that HCoV-EMC is a novel CoV species. More intensive surveillance studies in bats and other animals may reveal the natural host of HCoV-EMC.

Figure 1

Genome organizations of HCoV-EMC and other betaCoVs. Papain-like proteases (PL1^pro, PL2^pro and PL^pro), chymotrypsin-like protease (3CL^pro) and RNA-dependent RNA polymerase (RdRp) are represented by orange boxes. Haemagglutinin esterase (HE), spike (S), envelope (E), membrane (M) and nucleocapsid (N) are represented by green boxes. Putative accessory proteins are represented by blue boxes. HCoV-EMC is shown in bold.

Figure 2

Phylogenetic analysis of HCoV-EMC. The trees were constructed by the neighbor-joining method using Kimura correction and bootstrap values calculated from 1000 trees. 318, 951, 600, 1491 and 510 amino acid positions in chymotrypsin-like protease (3CL^pro), RNA-dependent RNA polymerase (RdRp), helicase (Hel), spike (S) and nucleocapsid (N) respectively were included in the analysis. For 3CL^pro, S and N, the scale bars indicate the estimated number of substitutions per 20 amino acids. For RdRp and Hel, the scale bars indicate the estimated number of substitutions per 50 amino acids. PEDV, porcine epidemic diarrhea virus (NC_003436); Sc-BatCoV-512, Scotophilus bat coronavirus 512 (NC_009657); TGEV, transmissible gastroenteritis virus (NC_002306); FIPV, feline infectious peritonitis virus (AY994055); CCoV, canine coronavirus (GQ477367); PRCV, porcine respiratory coronavirus (DQ811787); Rh-BatCoV-HKU2, Rhinolophus bat coronavirus HKU2 (EF203064); Mi-BatCoV 1A, Miniopterus bat coronavirus 1A (NC_010437); Mi-BatCoV 1B, Miniopterus bat coronavirus 1B (NC_010436); Mi-BatCoV-HKU8, Miniopterus bat coronavirus HKU8 (NC_010438); Hi-BatCoV HKU10, Hipposideros bat coronavirus HKU10 (JQ989269); Ro-BatCoV HKU10, Rousettus bat coronavirus HKU10 (JQ989270); HCoV-229E, human coronavirus 229E (NC_002645); HCoV-NL63, human coronavirus NL63 (NC_005831); HCoV OC43, human coronavirus OC43 (NC_005147); BCoV, bovine coronavirus (NC_003045); AntelopeCoV, sable antelope coronavirus (EF424621); GiCoV, giraffe coronavirus (EF424622); ECoV, equine coronavirus (NC_010327); PHEV, porcine hemagglutinating encephalomyelitis virus (NC_007732); MHV, murine hepatitis virus (NC_001846); RCoV, rat coronavirus (NC_012936); RbCoV HKU14, rabbit coronavirus HKU14 (NC_017083); HCoV-HKU1, human coronavirus HKU1 (NC_006577); Ty-BatCoV-HKU4, Tylonycteris bat coronavirus HKU4 (NC_009019); Pi-BatCoV-HKU5, Pipistrellus bat coronavirus HKU5 (NC_009020); SARS CoV, SARS-related human coronavirus (NC_004718); SARSr-Rh-BatCoV HKU3, SARS-related Rhinolophus bat coronavirus HKU3 (DQ022305); SARSr CoV CFB, SARS-related Chinese ferret badger coronavirus (AY545919); SARSr-CiCoV, SARS-related palm civet coronavirus (AY304488); Ro-BatCoV-HKU9, Rousettus bat coronavirus HKU9 (NC_009021); IBV, infectious bronchitis virus (NC_001451); IBV-partridge, partridge coronavirus (AY646283); TCoV, turkey coronavirus (NC_010800); IBV-peafowl, peafowl coronavirus (AY641576); BWCoV-SW1, beluga whale coronavirus SW1 (NC_010646); ALCCoV, Asian leopard cat coronavirus (EF584908); BuCoV HKU11, bulbul coronavirus HKU11 (FJ376619); ThCoV HKU12, thrush coronavirus HKU12 (FJ376621); MunCoV HKU13, munia coronavirus HKU13 (FJ376622); PorCoV HKU15, porcine coronavirus HKU15 (NC_016990); WECoV HKU16, white-eye coronavirus HKU16 (NC_016991); SpCoV HKU17, sparrow coronavirus HKU17 (NC_016992); MRCoV HKU18, magpie robin coronavirus HKU18 (NC_016993); NHCoV HKU19, night heron coronavirus HKU19 (NC_016994); WiCoV HKU20, wigeon coronavirus HKU20 (NC_016995); CMCoV HKU21, common moorhen coronavirus HKU21 (NC_016996).