X gene mutation Scattered in DDB1 Binding domain of x protein in Chronic Hepatitis-B and Cirrhosis patients

Introduction: HBx (X gene product) is a multifunctional regulator protein of hepatitis B virus. HBx direct or indirect interaction with cellular proteins such as DNA binding protein 1 (DDB1) may mediate its role in virus replication. According to previous studies, The DDB1 binding domain on HBx was located in the positions HBx88–100 peptide. Considering the DDB1 involvement in DNA repair and cell cycle regulation, it seems that occurrence mutation in c-terminal of x gene may influence the HBX interaction with DDB1 and disrupts all activities of DDB1. In present study we detect some mutation in DDB1 binding domain on HBx in a population of chronic HBV and Cirrhosis related to HBV. Materials and Methods: Sera from 68 patients with chronic HBV infection and 34 HBV-related cirrhotic were collected from the eligible cases (N=50) referred to the academic hospitals of Gorgan city, Northeast of Iran. These samples were analyzed by direct sequencing of semi-nested polymerase chain reaction amplification of x gene to determine the frequency of naturally occurring HBV x gene mutations. Results: We found occurrence of A1635T mutation in DDB1 binding domain on HBx. A1635T mutation resulted in amino acid (aa) 88(Ile to Phe substitution. Also a double T1639C/T1638C mutation caused to amino acid (aa) 89 (Leu to Pro substitution detected in one cirrhotic case. Conclusions: Mutations in the hepatitis B virus (HBV) x gene may influence disease activity by altering HBx-DDB1 interaction sites. In summary, A1635T mutation in the DDB1 binding domain on HBx of X gene can be frequently detected in HBV-related cirrhotic patients compare to chronic HBV patients.

کلیدواژه ها:

Hepatitis B virus ، X gene ، DNA binding protein 1 (DDB1) ، chronic HBV ، Cirrhosis