Hydrogen sulfide inhibits human T-cell leukemia virus type-1 (HTLV-1) protein expression via regulation of ATG4B

J Med Virol. 2023 Jan;95(1):e28176. doi: 10.1002/jmv.28176. Epub 2022 Oct 4.


Hydrogen sulfide (H2 S) is a redox gasotransmitter. It has been shown that H2 S has a key role in host antiviral defense by inhibiting interleukin production and S-sulfhydrating Keap1 lead to Nrf2/ARE pathway activation. However, it is yet unclear whether H2 S can play an antiviral role by regulating autophagy. In this study, we found that exogenous H2 S decreased the expression of human T-cell leukemia virus type-1 (HTLV-1) protein and HTLV-1 induced autophagosomes accumulation. Transmission electron microscope assays indicated that autophagosomes accumulation decreased after H2 S administration. HTLV-1-transformed T-cell lines had a high level of CSE (H2 S endogenous enzyme) which could be induced in Hela by HTLV-1 infection. Immunoblot demonstrated that overexpression of CSE inhibited HTLV-1 protein expression and autophagy. And we got the opposite after CSE knockdown. Meanwhile, H2 S could not restrain the autophagy when ATG4B had a mutant at its site of 89. In a word, these results suggested that H2 S modulated HTLV-1 protein expression via ATG4B. Therefore, our findings suggested a new mechanism by which H2 S defended against virus infection.

Keywords: ATG4B; autophagy; human T-cell leukemia virus type 1; hydrogen sulfide.

MeSH terms

  • Antiviral Agents / metabolism
  • Autophagy-Related Proteins / genetics
  • Cysteine Endopeptidases / metabolism
  • Human T-lymphotropic virus 1* / physiology
  • Humans
  • Hydrogen Sulfide* / metabolism
  • Hydrogen Sulfide* / pharmacology
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Leukemia, T-Cell*
  • NF-E2-Related Factor 2 / metabolism


  • Hydrogen Sulfide
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Antiviral Agents
  • ATG4B protein, human
  • Autophagy-Related Proteins
  • Cysteine Endopeptidases