Characteristics of MERS-CoV escape mutants under selective pressure of neutralizing antibody

Identification: Park, Woo-Jung


Description

 

Characteristics of MERS-CoV escape mutants under selective pressure of neutralizing antibody
 
Woo-Jung Park1, Han-Seam Lee1, Jeong-Sun Yang1, Joo-Yeon Lee 1*
1Division of Emerging Infectious Disease & Vector Research, Center for Infectious Diseases Research, National Institute of Health, Korea CDC, Cheongju-si, South Korea
*Corresponding Author: Joo-Yeon Lee, E-mail: ljyljy@nih.go.kr
 
The receptor binding domain (RBD) of the spike (S) glycoprotein of MERS-CoV is a major target of protective immunity in human. Although a large number of neutralizing antibodies (nAbs) have been developed, viral replication in the presence of a monoclonal antibody (mAb) is able to emerge viral escape variants. In previous study, we developed mAb with high neutralizing activity for MERS-CoVs. Therefore, to investigate virus mutation in the presence of nAb, we passaged serially for EMC strain and Korean isolate (KNIH_002) under selective pressure and then isolated escape mutants in the presence of antibody. Those mutants were analyzed for S gene sequence. For Korean isolate, all of eight escape mutants (002-1EM) were mutated only L506H of RBD region. Interestingly, for EMC strain, eight escape mutants were showed various genetic change. EMC-1EM mutated at L506F, T512I, and E513A of RBD region. EMC-4EM mutated at R511S and T512A of RBD region. EMC-6EM mutated at L506F, R511L, and E513A of RBD region. Also, neutralizing activity of all escape mutants with mutation of RBD region was more reduced clearly than those of parent virus. These data indicate that MERS-CoVs can sufficiently mutate in the presence of suitable neutralizing antibody, therefore, it needs to consider the prevention of escape variants for immunotherapy strategy on neutralizing antibody
 
Funding
This work was supported by grants from the intramural research fund of the Korea national institute of health (2016-NG47002-00)
 
 

 

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