Common RNA replication signals exist among group 2 coronaviruses: evidence for in vivo recombination between animal and human coronavirus molecules.
5' and 3' UTR sequences on the coronavirus genome are known to carry cis-acting elements for DI RNA replication and presumably also virus genome replication. 5' UTR-adjacent coding sequences are also thought to harbor cis-acting elements. Here we have determined the 5' UTR and adjacent 289-nt sequences, and 3' UTR sequences, for six group 2 coronaviruses and have compared them to each other and to three previously reported group 2 members. Extensive regions of highly similar UTR sequences were found but small regions of divergence were also found indicating group 2 coronaviruses could be subdivided into those that are bovine coronavirus (BCoV)-like (BCoV, human respiratory coronavirus-OC43, human enteric coronavirus, porcine hemagglutinating encephalomyelitis virus, and equine coronavirus) and those that are murine hepatitis virus (MHV)-like (A59, 2, and JHM strains of MHV, puffinosis virus, and rat sialodacryoadenitis virus). The 3' UTRs of BCoV and MHV have been previously shown to be interchangeable. Here, a reporter-containing BCoV DI RNA was shown to be replicated by all five BCoV-like helper viruses and by MHV-H2 (a human cell-adapted MHV strain), a representative of the MHV-like subgroup, demonstrating group 2 common 5' and 3' replication signaling elements. BCoV DI RNA, furthermore, acquired the leader of HCoV-OC43 by leader switching, demonstrating for the first time in vivo recombination between animal and human coronavirus molecules. These results indicate that common replication signaling elements exist among group 2 coronaviruses despite a two-cluster pattern within the group and imply there could exist a high potential for recombination among group members.
Department of Microbiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-0845, USA.
Hung-Yi
HY
Wu
James S
JS
Guy
Dongwan
D
Yoo
Reinhard
R
Vlasak
Ena
E
Urbach
David A
DA
Brian
D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D017934:Coronavirus / Q000145:classification* / Q000235:genetics*; D003673:Defective Viruses; D004742:Enhancer Elements, Genetic; D006378:Helper Viruses; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D034622:RNA Interference; D012367:RNA, Viral / Q000096:biosynthesis*; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D014779:Virus Replication
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D012367:RNA, Viral