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

Hydrogen sulfide (H2S) is a redox gasotransmitter. It has been shown that H2S 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 H2S can play an antiviral role by regulating autophagy. In this study, we found that exogenous H2S 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 H2S administration. HTLV-1-transformed T-cell lines had a high level of CSE (H2S 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, H2S could not restrain the autophagy when ATG4B had a mutant at its site of 89. In a word, these results suggested that H2S modulated HTLV-1 protein expression via ATG4B. Therefore, our findings suggested a new mechanism by which H2S defended against virus infection.