Interferon-stimulated gene factor 3 complex is required for the induction of sterile α motif and HD domain-containing protein 1 expression by interferon-α in SMMC-7721 cells

Abstract

Sterile α motif and HD domain-containing protein 1 (SAMHD1) is a novel intrinsic restriction factor that inhibits the replication of certain retroviruses and DNA viruses through its deoxynucleoside triphosphate triphosphohydrolase activity. A previous study by our group showed that SAMHD1 restrained hepatitis B virus replication and interferon (IFN)-α induced SAMHD1 expression in liver cells. However the mechanisms of SAMHD1 upregulation by IFN-α in liver cells have remained elusive. The present study demonstrated that IFN-α treatment increased SAMHD1 mRNA levels in SMMC-7721 cells in a time-dependent manner. Knockdown of STAT1 inhibited the induction of SAMHD1 expression by IFN-α in SMMC-7721 cells. STAT2 silencing also suppressed the induction of SAMHD1 expression by IFN-α in SMMC-7721 cells. Furthermore, the induction of SAMHD1 expression in SMMC-7721 cells by IFN-α was found to be dependent on IFN-regulatory factor 9 (IRF9). In conclusion, these results suggested that the interferon-stimulated gene factor 3 complex, which consists of STAT1, STAT2 and IRF9, is required for the induction of SAMHD1 expression by IFN-α in SMMC-7721 cells.