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Background <p>The Aedes albopictus C6/36 cell line is model system for studying mosquito-borne viruses. These cells exhibit high permissiveness to Japanese encephalitis virus (JEV), supporting robust viral replication and producing a significant viral load.</p> Methods <p>Given C6/36 cells established susceptibility, this study employed 4D label-free quantitative proteomics to investigate the underlying mechanisms that enable C6/36 cells to be readily cultured and facilitate efficient JEV infection. C6/36 cells were infected with JEV at MOI of 0.5 and harvested at 0,6,12, and 24 hours post-infection (HPI) for 4D label-free quantitative proteomics analysis.</p> Results <p>Proteomic data analysis revealed that differentially expressed proteins were primarily involved in signal transduction mechanisms, innate immune responses, metabolism, and the synthesis, transport, and catabolism of secondary metabolites. JEV infection downregulated several proteins involved in DNA replication, including proliferating cell nuclear antigen (PCNA), DNA polymerase epsilon subunit 3 (POLε3), and DNA primase large subunit (PRI2), thereby inhibiting DNA replication signaling pathways and contributing to increased JEV replication. JEV infection also suppressed Toll-like receptors (TLRs), key components of the innate immune system. Specifically, TLR2, TLR4, TLR7, and TLR13 were significantly downregulated, thereby suppressing the innate immune response.</p> Conclusion <p>Our results suggest that JEV infection impairs DNA replication and innate immune responses, particularly the inhibition of PRI2 and POLε3, leading to increased JEV replication and potentially a key mechanism of JEV pathogenesis. Elucidating the interactions between JEV and the host DNA replication and immune system will facilitate the development of more effective JEV prevention and treatment strategies.</p>

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Signaling pathway of DNA replication and toll-like receptors was inhibited in C6/36 cells infected with Japanese encephalitis virus

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月4日

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  • Yan Gao,
  • Xinxin Shi,
  • Bing Li,
  • Ning Shi,
  • Guanyu Zhao,
  • Zhuoxin Li,
  • Xiangshu Qiu,
  • Jiaqi Zhang,
  • Junduo Bao,
  • Xu Gao,
  • He Zhang,
  • Huijun Lu

摘要

Background

The Aedes albopictus C6/36 cell line is model system for studying mosquito-borne viruses. These cells exhibit high permissiveness to Japanese encephalitis virus (JEV), supporting robust viral replication and producing a significant viral load.

Methods

Given C6/36 cells established susceptibility, this study employed 4D label-free quantitative proteomics to investigate the underlying mechanisms that enable C6/36 cells to be readily cultured and facilitate efficient JEV infection. C6/36 cells were infected with JEV at MOI of 0.5 and harvested at 0,6,12, and 24 hours post-infection (HPI) for 4D label-free quantitative proteomics analysis.

Results

Proteomic data analysis revealed that differentially expressed proteins were primarily involved in signal transduction mechanisms, innate immune responses, metabolism, and the synthesis, transport, and catabolism of secondary metabolites. JEV infection downregulated several proteins involved in DNA replication, including proliferating cell nuclear antigen (PCNA), DNA polymerase epsilon subunit 3 (POLε3), and DNA primase large subunit (PRI2), thereby inhibiting DNA replication signaling pathways and contributing to increased JEV replication. JEV infection also suppressed Toll-like receptors (TLRs), key components of the innate immune system. Specifically, TLR2, TLR4, TLR7, and TLR13 were significantly downregulated, thereby suppressing the innate immune response.

Conclusion

Our results suggest that JEV infection impairs DNA replication and innate immune responses, particularly the inhibition of PRI2 and POLε3, leading to increased JEV replication and potentially a key mechanism of JEV pathogenesis. Elucidating the interactions between JEV and the host DNA replication and immune system will facilitate the development of more effective JEV prevention and treatment strategies.