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"Defective" mutations of hepatitis D viruses in chronic hepatitis D patients

World Journal of Gastroenterology 2005年第11期11卷 1658-1662页

作者： Jaw-Ching Wu Sheng-Chieh Hsu Shen-Yung Wang Yi-Hsiang Huang i-jane sheen Hsuan-Hui Shih Wan-Jr Syu institute of Clinical Medicine Department of Medical Research and Education Taipei Veterans General Hospital Taipei Taiwan China Division of Gastroenterology School of Medicine National Yang-Ming University Taipei Taiwan China institute of Microbiology and immunology

AiM: To verify whether 'defective' mutations existed in hepatitis D virus (HDV).METHODS: Hepatitis delta antigen (HDAg)-codingsequences were amplified using Pfu DNA polymerases with proof-reading activities from sera of five patients with chronic hepatitis D. Multiple colonies were sequenced for each patient. Pfu analyzed a total of 270 HDV *** representative defective HDV clones were constructed in expression plasmids and transfected into a human hepatoma cell line. Cellular proteins were extracted and analyzed by Western ***: Four of five cases (80%) showed defective HDV genomes in their sera. The percentage of defective genomes was 3.7% (10/270). The majority (90%) of the defective mutations were insertions or deletions that resulted in frameshift and abnormal stop translation of the HDAg. The predicted mutated HDAg ranged from 45amino acids to ＞214 amino acids in length. Various domains of HDAg associated with viral replication or packaging were affected in different HDV isolates. Western blot analysis showed defected HDAg in predicted ***: 'Defective' viruses do exist in chronic HDV infected patients, but represented as minor strains. The clinical significance of the 'defected' HDV needs further study to evaluate.

关键词： HDV DNA AiM

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