West Nile virus vaccine candidates attenuated by dinucleotide enrichment are immunogenic and protective against lethal infection.

ABSTRACT: West Nile virus (WNV) poses a global public health threat. This study demonstrates that the WNV RNA tolerates CpG and UpA dinucleotide enrichment in different genomic regions resulting in attenuation of CpG- and CpG/UpA-enriched variants. Attenuation was zinc finger antiviral protein 1 (ZAP)-dependent, and ZAP knockout (ZAP-KO) cells were used to generate high-titer stocks. Ten enriched variants, with permuted control and wild-type (WT) viruses, were screened in immunocompetent mice upon intraperitoneal injection. In contrast to lethal WNV-WT and permuted viruses, the E-MAX variant, with the RNA region encoding envelope (E) protein enriched both with CpG and UpA, caused no mortality. E-MAX was immunogenic and protective against lethal challenge. Stability of enriched dinucleotides was conf

SUBMITTER: Le NPK 

PROVIDER: S-EPMC12513643 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature