简介：AbstractAfrican swine fever virus (ASFV) is the causative agent of African swine fever, a highly fatal hemorrhagic disease of pigs, which has resulted in great economic losses to the global pork industry, especially in Asia. ASFV particles are comprised of multiple layers encompassing the genomic DNA. Though the capsid structure has been determined, very little is known about the structure of the core shell. The precursor polyprotein pp62 is the structural component of the core shell that gives rise to the p35 and p15 proteins. Herein, we describe the crystal structure of p15 at a resolution of 2.2 Å. The structure of p15 exhibits as a trimeric conformation that is mainly mediated by intermolecular disulfide bonds and supported by multiple hydrogen bond interactions. The button conformation on the surface of adjacent molecules may also play a role in trimeric formation of the ASFV p15. The center of the p15 trimer exhibits opposite electrostatic characteristics on each side. These findings benefit our understanding of ASFV core shell assembly and will aid in the design of antiviral drugs and vaccines.

简介：AbstractBackground:Hepatitis B core-related antigen (HBcrAg) is a promising disease-monitoring marker for chronic hepatitis B (CHB). We investigated correlations between HBcrAg with antiviral efficacy and virological and histological variables.Methods:One hundred and forty-five CHB patients from the mainland of China between August 2013 and September 2016 who underwent liver biopsy received entecavir therapy and had paired liver biopsy at 78 weeks. We analyzed correlations between HBcrAg and virological and histological variables in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. We also explored the predictors of HBeAg loss after 78 weeks of antiviral therapy. Pearson correlation analysis and logistic forward stepwise regression were the main statistic methods.Results:HBeAg-positive patients (n = 93) had higher baseline HBcrAg (median 7.4 vs. 5.3 log10 U/mL P < 0.001) and greater HBcrAg declines (median 1.6 vs. 0.9 log10 U/mL P= 0.007) than HBeAg-negative patients after 78 weeks of therapy. At baseline, HBcrAg correlated with hepatitis B virus (HBV) DNA in both HBeAg-positive (r = 0.641, P < 0.001) and -negative patients (r = 0.616, P < 0.001), with hepatitis B surface antigen (HBsAg) in HBeAg-positive patients (r = 0.495, P < 0.001), but not with anti-hepatitis B virus core antibody (anti-HBc). Weak correlations existed between HBcrAg, histology activity index (HAI; r = 0.232, P= 0.025), and Ishak fibrosis score (r= -0.292, P= 0.005) in HBeAg-positive patients. At 78 weeks, significant correlations existed only between HBcrAg and anti-HBc in HBeAg-positive (r = -0.263, P = 0.014) and HBeAg-negative patients (r= -0.291, P= 0.045). Decreased HBcrAg significantly correlated with reduced HBV DNA (r= 0.366, P= 0.001; r= 0.626, P < 0.001) and HBsAg (r = 0.526, P = 0.001; r = 0.289, P = 0.044) in HBeAg-positive and -negative patients, respectively, and with reduced HAI in HBeAg-positive patients (r = 0.329, P = 0.001). Patients with HBeAg loss (n = 29) showed a larger reduction in HBcrAg than those without (median 2.3 vs. 1.3 log10 U/mL, P = 0.001). In multivariate analysis, decreased HBcrAg was an independent predictor of HBeAg loss (P = 0.005).Conclusions:HBcrAg reflects viral replication and protein production. Decreased HBcrAg could predict HBeAg loss after antiviral therapy.Trial registration:Clinical Trials.gov: NCT01962155; https://www.clinicaltrials.gov/ct2/show/NCT01962155?term=NCT01962155&draw=2&rank=1