Eukaryotic translation elongation factor 1 alpha 1 facilitates coxsackievirus B replication through interacting with PABP, viral protein 3 CD and viral RNA

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Abstract
Viral myocarditis, often caused by Coxsackievirus B (CVB), is the leading cause of dilated cardiomyopathy and heart failure. Despite extensive research, the pathogenesis of CVB infection remains incompletely understood. Our previous study found that Anisomycin inhibits CVB replication by promoting the degradation of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1). However, the precise mechanism through which eEF1A1 facilitates the replication of CVB remains to be fully elucidated. Here, we demonstrated that upregulated eEF1A1 is required for CVB3 replication. In vitro transcription and RNA pulldown assay demonstrated that eEF1A1 binds to the 5' cloverleaf region of CVB3 RNA. We observed that eEF1A1 interacts with double-stranded viral RNA, viral precursor protein 3 CD, and poly(A)-binding protein (PABP), which enhances its interaction with 3 CD. We show that CVB3 upregulates eEF1A1 expression by activating NF-κB. Chromosome-immunoprecipitation assay confirmed that NF-κB p65 binds to the EEF1A1 promoter. Luciferase reporter assays validated that NF-κB up-regulates EEF1A1 transcription. We further showed that eEF1A1 promotes CVB3 replication through interacting with viral RNA, 3 CD, and cellular protein PABP. This study highlights that eEF1A1, which is essential for cellular translation, is manipulated by CVB3 to promote viral replication. These findings suggest that targeting eEF1A1 could be a potential antiviral strategy against CVB infection.
Funding Information
  • National Natural Science Foundation of China (82172247)
  • National Natural Science Foundation of China (81971920)
  • National Natural Science Foundation of China (82072278)
  • National Natural Science Foundation of China (82302502)
  • National Natural Science Foundation of China (82202493)
  • Natural Science Foundation of Heilongjiang Province of China (YQ2023H003)
  • Major Project of Guangzhou National Laboratory (GZNL2024A01016)
  • Major Project of Guangzhou National Laboratory (GZNL2025C01015)
  • Guangdong Special Support Plan on Young Top-notch Talents (2024TQ08A676)

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