Chronic hepatitis B (CHB) patients treated with
interferon shows encouraging results. However, its clinical efficacy is limited by significant individual differences in treatment responses. We identified an
interferon-inducible effector, TRIM22, as the likely causal target of such differential responses. We found that TRIM22 was highly expressed in
interferon-responsive patients and negatively correlated with HBV
DNA and
HBeAg serum levels. Stable cells overexpressing TRIM22 carried significantly less
HBsAg,
HBeAg, and HBV
DNA, and cells with knocked-down TRIM22 by
shRNA displayed higher levels of these markers than controls. Integrated bioinformatics analysis and subsequent experiments revealed that TRIM22 overexpression significantly increased the supernatant levels of IL-1β and
IL-8, two important
cytokines of NOD2/NF-κB pathway involved in
interferon-induced
antiviral activities. We identified three candidate
microRNAs binding to
3'UTR of TRIM22 at various locations through typical imperfect paring using the TargetScan program. MiR-548c-3p appeared to be highly expressed, while the TRIM22 level was low in the suboptimal response group of CHB patients. The
Luciferase reporter assay revealed an interaction between miR-548c-3p and the
3'UTR of TRIM22, leading to a controlled suppression of TRIM22 endogenous expression. This resulted in
interferon's substantially weakened therapeutic efficacy, as indicated by the elevation of the serum levels of
HBsAg,
HBeAg and HBV
DNA in miR-548c-3p-transfected HepAD38 cells. Our study demonstrated that a particular miR-548c-3p is the key negative regulator of TRIM22 in CHB patients with a weak response to
interferon treatment, providing a novel marker and target in
interferon-α
therapy evaluation.