Knockdown of mitogen-activated protein kinase kinase 3 negatively regulates hepatitis a virus replication

Tatsuo Kanda, Reina Sasaki-Tanaka, Ryota Masuzaki, Naoki Matsumoto, Hiroaki Okamoto, Mitsuhiko Moriyama

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Zinc chloride is known to be effective in combatting hepatitis A virus (HAV) infection, and zinc ions seem to be especially involved in Toll-like receptor (TLR) signaling pathways. In the present study, we examined this involvement in human hepatoma cell lines using a human TLR signaling target RT-PCR array. We also observed that zinc chloride inhibited mitogen-activated protein kinase 3 (MAP2K3) expression, which could downregulate HAV replication in human hepatocytes. It is possible that zinc chloride may inhibit HAV replication in association with its inhibition of MAP2K3. In that regard, this study set out to determine whether MAP2K3 could be considered a modulating factor in the development of the HAV pathogen-associated molecular pattern (PAMP) and its triggering of interferon-β production. Because MAP2K3 seems to play a role in antiviral immunity against HAV infection, it is a promising target for drug development. The inhibition of MAP2K3 may also prevent HAV patients from developing a severe hepatitis A infection.

Original languageEnglish
Article number7420
JournalInternational Journal of Molecular Sciences
Issue number14
Publication statusPublished - 2 Jul 2021


  • HAV
  • MAP2K3
  • Toll-like receptor
  • Zinc chloride


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