Optimization of the nucleocapsid protein sequences of human measles virus and canine distemper virus to human and canine codon usage bias increases sequence identity and protein expression (145.3)

Amino acids are coded for by two to six different RNA codons and frequency of codon use, known as codon usage bias (CUB), varies between species. Since viruses do not have tRNAs, the translation of viral proteins depends upon utilization of host tRNA, and is impacted by the host’s CUB. We are investigating the importance of codon usage in morbilliviral host adaptation and pathogenicity. Previously we determined that human CUB had significantly higher relative adaptiveness for 6 of 7 CDV proteins than canine CUB. For this study we constructed nucleic acid sequences for HMV and CDV N proteins that were optimized to human and canine CUB. For both viral N proteins, the human and canine codon optimized sequences had increased nucleic acid and codon identity compared to wild type. In addition, codon optimization of the CDV N protein to either the human or canine CUB increased its nucleic acid identity to the wild type (WT) HMV N protein from 66.3% (HMV WT vs CDV WT) to 71.8% (Human CUB vs WT) and 72.2% (Canine CUB vs WT). Finally, protein expression from human and canine CUB optimized HMV and CDV N protein nucleic acid sequences transfected into human (293 HEK) cells was increased over that of the WT constructs. These results indicate that further adaptation of HMV and CDV to the mammalian CUB could potentially enhance viral expression. Grant Funding Source : Supported by Department of Defense Threat Reduction Agency