Enhanced replication fitness of MERS-CoV clade B over clade A strains in camelids explains the dominance of clade B strains in the Arabian Peninsula
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Fecha de publicación
2022-02-01ISSN
2222-1751
Resumen
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.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
English
Materias (CDU)
619 - Veterinaria
Páginas
16
Publicado por
Taylor & Francis Open Access
Publicado en
Emerging Microbes and Infections
Citación
Te, Nigeer, Jordi Rodon, Mónica Pérez, Joaquim Segalés, Júlia Vergara-Alert, and Albert Bensaid. 2022. "Enhanced Replication Fitness Of MERS-Cov Clade B Over Clade A Strains In Camelids Explains The Dominance Of Clade B Strains In The Arabian Peninsula". Emerging Microbes & Infections 11 (1): 260-274. doi:10.1080/22221751.2021.2019559.
Número del acuerdo de la subvención
EC/PF7/115760/EU/Zoonotic Anticipation and Preparedness Initiative/ZAPI
EC/H2020/731014/EU/Veterinary Biocontained facility Network for excellence in animal infectiology research and experimentation/VetBioNet
Program
Sanitat Animal
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