tailieunhanh - Báo cáo y học: " Prediction of conformational changes by single mutation in the hepatitis B virus surface antigen (HBsAg) identified in HBsAg-negative blood donors"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Prediction of conformational changes by single mutation in the hepatitis B virus surface antigen (HBsAg) identified in HBsAg-negative blood donors | le et al. Virology Journal 2010 7 326 http content 7 1 326 VIROLOGY JOURNAL RESEARCH Open Access Prediction of conformational changes by single mutation in the hepatitis B virus surface antigen HBsAg identified in HBsAg-negative blood donors Susan I Ie Meta D Thedjaf Martono Roni David H Muljono Abstract Background Selection of hepatitis B virus HBV by host immunity has been suggested to give rise to variants with amino acid substitutions at or around the a determinant of the surface antigen HBsAg the main target of antibody neutralization and diagnostic assays. However there have never been successful attempts to provide evidence for this hypothesis partly because the 3 D structure of HBsAg molecules has not been determined. Tertiary structure prediction of HBsAg solely from its primary amino acid sequence may reveal the molecular energetic of the mutated proteins. We carried out this preliminary study to analyze the predicted HBsAg conformation changes of HBV variants isolated from Indonesian blood donors undetectable by HBsAg assays and its significance compared to other previously-reported variants that were associated with diagnostic failure. Results Three HBV variants T123A M133L and T143M and a wild type sequence were analyzed together with frequently emerged variants T123N M133I M133T M133V and T143L. Based on the Jameson-Wolf algorithm for calculating antigenic index the first two amino acid substitutions resulted in slight changes in the antigenicity of the a determinant while all four of the comparative variants showed relatively more significant changes. In the pattern T143M changes in antigenic index were more significant both in its coverage and magnitude even when compared to variant T143L. These data were also partially supported by the tertiary structure prediction in which the pattern T143M showed larger shift in the HBsAg second loop structure compared to the others. Conclusions Single amino acid substitutions within or near the