Synonymous Codon Changes in Measles (HMV) and Canine Distemper (CDV) Viral Nucleic Acid Sequences Result in Gene‐Specific Changes in Levels of Viral Protein Expression

Abstract

The purpose of this study was to characterize the effects of human and canine codon optimization on expression of viral proteins from HMV and CDV nucleic acid sequences. All the codon changes made were synonymous in that the amino acid coded for was unchanged. The human and canine CUB optimized HMV and CDV sequences had increased nucleic acid and codon identity as compared to the WT sequences. Protein expression from human and canine CUB optimized and sub‐optimized constructs of the N, F, M, H and P/C proteins was assessed in transfected human (293 HEK) and canine (A‐72) cells using fluorescence, Cellomic and, for proteins for which antibodies were available, western analysis.Results1) codon optimization increased protein expression of HMV and CDV N and F proteins in both cell lines; 2) synonymous codon changes did not affect expression of the HMV and CDV P and C and the HMV M proteins, but both optimization and sub‐optimization to canine CUB increased expression of the CDV M protein in human cells; 3) synonymous codon changes increased expression of the HMV H protein in both cell lines, but did not significantly affect CDV H protein expression. Overall both CUB optimization and sub‐optimization affected protein expression independent of viral infection in ways that varied with the gene and cell type, and differed between HMV and CDV. These results indicate that synonymous codon changes in viral nucleic acid sequences can alter protein expression in a variety of ways, some of which are likely to impact viral pathogenicity.Support or Funding InformationThis project was sponsored by the Department of Defense Threat Reduction Agency. The content of the information does not necessarily reflect the position or the policy of the federal government, and no official endorsement should be inferred.