tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2021 Dec 17;1-51.
doi: 10.1080/22221751.2021.2019559. Online ahead of print.
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
Nigeer Te[SUP] 1 [/SUP], Jordi Rodon[SUP] 1 [/SUP], Mónica Pérez[SUP] 1 [/SUP], Joaquim Segalés[SUP] 2 3 [/SUP], Júlia Vergara-Alert[SUP] 1 [/SUP], Albert Bensaid[SUP] 1 [/SUP]
Affiliations
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 decreased 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.
Keywords: IFN; MERS-CoV; Middle East respiratory syndrome coronavirus; ORF4a; alpaca; strain.
. 2021 Dec 17;1-51.
doi: 10.1080/22221751.2021.2019559. Online ahead of print.
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
Nigeer Te[SUP] 1 [/SUP], Jordi Rodon[SUP] 1 [/SUP], Mónica Pérez[SUP] 1 [/SUP], Joaquim Segalés[SUP] 2 3 [/SUP], Júlia Vergara-Alert[SUP] 1 [/SUP], Albert Bensaid[SUP] 1 [/SUP]
Affiliations
- PMID: 34918620
- DOI: 10.1080/22221751.2021.2019559
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 decreased 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.
Keywords: IFN; MERS-CoV; Middle East respiratory syndrome coronavirus; ORF4a; alpaca; strain.