ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) continues infecting humans and dromedary camels. While MERS-CoV strains from the Middle East region are subdivided into two clades (A and B), all the contemporary epidemic viruses belong to clade B. Thus, MERS-CoV clade B strains may display adaptive advantages over clade A in humans and/or reservoir hosts. To test this hypothesis in vivo , we compared an early epidemic clade A strain (EMC/2012) with a clade B strain (Jordan-1/2015) in an alpaca model monitoring virological and immunological parameters. Further, the Jordan-1/2015 strain has a partial amino acid (aa) deletion in the double-stranded (ds) RNA binding motif of the open reading frame ORF4a protein. Animals inoculated with the Jordan-1/2015 variant had higher MERS-CoV replicative capabilities in the respiratory tract and larger nasal viral shedding. In the nasal mucosa, the Jordan-1/2015 strain caused an early IFN response, suggesting a role for ORF4a as a moderate IFN antagonist in vivo . However, both strains elicited maximal transcription of antiviral interferon-stimulated genes (ISGs) at the peak of infection on 2 days post inoculation, correlating with subsequent decreases in tissular viral loads. Genome alignment analysis revealed several clade B-specific amino acid substitutions occurring in the replicase and the S proteins, which could explain a better adaptation of clade B strains in camelid hosts. Differences in replication and shedding reported herein indicate a better fitness and transmission capability of MERS-CoV clade B strains than their clade A counterparts.
【저자키워드】 MERS-CoV, Middle East respiratory syndrome Coronavirus, IFN, alpaca, strain, orf4a, 【초록키워드】 adaptive, Antiviral, Human, Transcription, variant, Infection, viral shedding, Transmission, nasal, virus, RNA, Replication, Protein, Epidemic, animal, clade, respiratory tract, in vivo, moderate, nasal mucosa, ISGs, binding, Amino acid, Hypothesis, Analysis, IFN response, Middle East, Virological, Frame, viral loads, S proteins, hosts, respiratory syndrome coronavirus, motif, while, immunological parameters, interferon-stimulated gene, amino acid substitution, infecting, decrease, difference, post inoculation, caused, reported, inoculated, subsequent, elicited, explain, replicative, double-stranded, 【제목키워드】 Replication, clade, Arabian Peninsula, enhanced, explain,