Résumé
Objective:To study the role and mechanism of heat shock protein 70 (HSP70) in apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B)-mediated inhibition of hepatitis B virus(HBV) replication.Methods:The interaction between HSP70 and APOBEC3B was analyzed by co-immunopreciptation (Co-IP) and GST pull-down. After treating Huh7 cells with siHSP70 or HSP70 inhibitor VER155008 or overexpressing HSP70 in Huh7 cells, changes in the antiviral effect of APOBEC3B were detected by Southern blot and real-time PCR; the deaminase activity of APOBEC3B was tested by differential DNA denaturation PCR(3D-PCR) and clone sequencing.Results:HSP70 could bind to APOBEC3B. Overexpression of HSP70 promoted the deaminase activity and anti-HBV activity of APOBEC3B. On the contrary, knockdown of HSP70 or using HSP70 inhibitor VER155008 would attenuate the deaminase activity and anti-HBV activity of APOBEC3B.Conclusions:HSP70 could promote the anti-HBV activity of APOBEC3B by enhancing the deaminase activity of APOBEC3B.
Résumé
ObjectiveTo investigate the difference in the distribution frequency of APOBEC3B copy number variations (CNVs) between patients with different outcomes after hepatitis B virus (HBV) infection and the role of APOBEC3B CNVs in clinical outcome. MethodsA total of 296 patients with acute self-limiting recovery after HBV infection and 819 patients with different stages of chronic HBV infection who visited The First Affiliated Hospital of Anhui Medical University from January 2016 to December 2017 were enrolled as acute self limiting recovery group and chronic HBV infection group, respectively, and their peripheral blood samples were collected. Among the 819 patients with chronic HBV injection, 444 had chronic hepatitis B (CHB), 252 had liver cirrhosis (LC), and 123 had hepatocellular carcinoma (HCC). The AccuCopy method was used to measure APOBEC3B CNVs in peripheral blood, and related clinical data were collected for all patients. The chi-square test was used for comparison of distribution frequency of APOBEC3B CNVs between groups. ResultsFor acute or chronic outcome after chronic HBV infection, the acute self limiting recovery group had a significantly lower proportion of patients with reduced or deleted APOBEC3B CNVs than the chronic HBV infection group (46.96% vs 58.00%, P=0.001 1). For disease progression after chronic HBV infection, the HCC group had the highest proportion of patients with deleted APOBEC3B CNVs of 22.76%, followed by the LC group (14.29%) and the CHB group (11.04%), and there was a significant difference between the three groups (χ2=11.85, P=0019). In the chronic HBV infection group, there was no significant difference in the distribution frequency of APOBEC3B CNVs between the patients with positive E-antigen and those with negative E-antigen(χ2=0639,P=0727). ConclusionAPOBEC3B CNV is associated with the outcome of chronic HBV infection, and reduced and deleted APOBEC3B CNV is a genetic susceptibility factor for chronicity and progression of HBV infection.
Résumé
ObjectiveTo investigate the difference in the distribution frequency of APOBEC3B copy number variations (CNVs) between patients with different outcomes after hepatitis B virus (HBV) infection and the role of APOBEC3B CNVs in clinical outcome. MethodsA total of 296 patients with acute self-limiting recovery after HBV infection and 819 patients with different stages of chronic HBV infection who visited The First Affiliated Hospital of Anhui Medical University from January 2016 to December 2017 were enrolled as acute self limiting recovery group and chronic HBV infection group, respectively, and their peripheral blood samples were collected. Among the 819 patients with chronic HBV injection, 444 had chronic hepatitis B (CHB), 252 had liver cirrhosis (LC), and 123 had hepatocellular carcinoma (HCC). The AccuCopy method was used to measure APOBEC3B CNVs in peripheral blood, and related clinical data were collected for all patients. The chi-square test was used for comparison of distribution frequency of APOBEC3B CNVs between groups. ResultsFor acute or chronic outcome after chronic HBV infection, the acute self limiting recovery group had a significantly lower proportion of patients with reduced or deleted APOBEC3B CNVs than the chronic HBV infection group (46.96% vs 58.00%, P=0.001 1). For disease progression after chronic HBV infection, the HCC group had the highest proportion of patients with deleted APOBEC3B CNVs of 22.76%, followed by the LC group (14.29%) and the CHB group (11.04%), and there was a significant difference between the three groups (χ2=11.85, P=0019). In the chronic HBV infection group, there was no significant difference in the distribution frequency of APOBEC3B CNVs between the patients with positive E-antigen and those with negative E-antigen(χ2=0639,P=0727). ConclusionAPOBEC3B CNV is associated with the outcome of chronic HBV infection, and reduced and deleted APOBEC3B CNV is a genetic susceptibility factor for chronicity and progression of HBV infection.