Synonymous SNPs of viral genes facilitate virus to escape host antiviral RNAi immunity

Abstract

Synonymous single nucleotide polymorphisms (SNPs) are involved in codon usage preference or mRNA splicing. Up to date, however, the role of synonymous SNPs in immunity remains unclear. To address this issue, the SNPs of white spot syndrome virus (WSSV) were characterized in shrimp in the present study. Our results indicated that there existed synonymous SNPs in the mRNAs of wsv151 and wsv226, two viral genes of WSSV. In the presence of SNP siRNA, wild-type siRNA, wild-type mRNA and SNP mRNA of wsv151 or wsv226, RNAi was significantly suppressed, showing that the synonymous SNPs of wsv151 and wsv226 played negative roles in host siRNA pathway due to mismatch of siRNA with its target. In insect cells, the mismatch, caused by synonymous SNPs of wsv151 or wsv226, between siRNA and its target inhibited the host RNAi. Furthermore, the data revealed that the co-injection of SNP siRNA and wild-type siRNA of wsv151 or wsv226 into WSSV-infected shrimp led to a significant increase of WSSV copies compared with that of SNP siRNA alone or wild-type siRNA alone, indicating that the synonymous SNPs of viral genes could be a strategy of virus escaping host siRNA pathway in shrimp in vivo. Therefore, our study provided novel insights into the underlying mechanism of virus escaping host antiviral RNAi immunity by synonymous SNPs of viral genes.\n\nAuthor SummaryOur results indicated that there existed synonymous SNPs in the mRNAs of wsv151 and wsv226, two viral genes of WSSV. In the presence of SNP siRNA, wild-type siRNA, wild-type mRNA and SNP mRNA of wsv151 or wsv226, RNAi was significantly suppressed, showing that the synonymous SNPs of wsv151 and wsv226 played negative roles in host siRNA pathway due to mismatch of siRNA with its target. In insect cells, the mismatch, caused by synonymous SNPs of wsv151 or wsv226, between siRNA and its target inhibited the host RNAi. Furthermore, the data revealed that the co-injection of SNP siRNA and wild-type siRNA of wsv151 or wsv226 into WSSV-infected shrimp led to a significant increase of WSSV copies compared with that of SNP siRNA alone or wild-type siRNA alone, indicating that the synonymous SNPs of viral genes could be a strategy of virus escaping host siRNA pathway in shrimp in vivo.