Human and Canine Codon Optimization of Measles and Canine Distemper Viral Nucleic Acid Sequences Increases Sequence Identity and Protein Expression Compared to Wild Type and Human Codon Sub‐Optimized Constructs

Abstract

The role of codon usage bias (CUB) in the host adaptation and pathogenicity of human measles virus (HMV) and canine distemper virus (CDV) is being investigated and compared. Analysis of nucleic acid sequences for HMV and CDV nucleoprotein (N) revealed that human and canine CUB optimized constructs, as compared to wild type (WT) and human CUB sub‐optimized constructs, were characterized by increased nucleic acid and codon identities, and increased protein expression when transfected into human (293 HEK) cells. The purpose of this study was to characterize human and canine codon optimized nucleic acid sequences of the MHV and CDV F, M, H,L and P/C proteins. All human and canine CUB optimized HMV and CDV nucleic acid sequences had increased nucleic acid and codon identity as compared to WT sequences. Protein expression in human cells transfected with human and canine CUB optimized constructs of the F, M, H and P/C proteins was assessed using florescence, Cellomic and where possible western analysis. Higher protein expression was present in cells transfected with the human and canine codon optimized constructs compared to cells transfected with HMV and CDV WT or HMV suboptimized constructs. These results suggest that further adaptation of HMV and CDV to the mammalian CUB could enhance viral protein expression and pathogenesis.