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

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.