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The role of mutations in core protein of hepatitis B virus in liver fibrosis.

Mohamadkhani A, Jazii FR, Poustchi H, Nouraein O, Abbasi S, Sotoudeh M, Montazeri G - Virol. J. (2009)

Bottom Line: Mutations in CTL epitopes and in phosphorylation sites of C-terminal domain of core protein also were associated with higher liver fibrosis (P = 0.003 and P = 0.04; Fisher's exact test for both).Patients with mutations in B cell and T helper epitopes did not show significant difference in the clinical features.Our data suggests that core protein mutations in CTL epitopes and C-terminal domain accompanied with higher stage of liver fibrosis may be due to alterations in the function of core protein.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institute of Genetic Engineering and Biotechnology Tehran, Iran. ashraf@ams.ac.ir

ABSTRACT
The core protein of hepatitis B virus encompasses B- and T-cell immunodominant epitopes and subdivided into two domains: the N-terminal and the functional C-terminal consisted phosphorylation sites. Mutations of the core gene may change the conformation of the core protein or cause alteration of important epitopes in the host immune response. In this study twenty nine men (mean age 40 +/- 9 years old) with chronic hepatitis B were recruited for direct sequencing of the core gene. Serum ALT and HBV DNA level were measured at the time of liver biopsy. The effects of core protein mutations on patients' characteristics and subsequently mutations in B cell, T helper and cytotoxic T lymphocyte (CTL) epitopes and also C-terminal domain of core protein on the activity of liver disease was evaluated. Liver fibrosis was significantly increased in patients with core protein mutation (1.0 +/- 0.8 vs 1.9 +/- 1.4 for mean stage of fibrosis P = 0.05). Mutations in CTL epitopes and in phosphorylation sites of C-terminal domain of core protein also were associated with higher liver fibrosis (P = 0.003 and P = 0.04; Fisher's exact test for both). Patients with mutation in C-terminal domain had higher serum ALT (62 +/- 17 vs 36 +/- 12 IU/l, p = 0.02). Patients with mutations in B cell and T helper epitopes did not show significant difference in the clinical features. Our data suggests that core protein mutations in CTL epitopes and C-terminal domain accompanied with higher stage of liver fibrosis may be due to alterations in the function of core protein.

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Related in: MedlinePlus

Predicted GO annotations for HBV core protein sequence, The PFP algorithm scored GO terms individually and includes information from distantly related sequences to HBV core protein. The function of each GO has been shown in table 5.
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Figure 1: Predicted GO annotations for HBV core protein sequence, The PFP algorithm scored GO terms individually and includes information from distantly related sequences to HBV core protein. The function of each GO has been shown in table 5.

Mentions: Core protein with the largest number of serine sites in C-terminal tail could be widely phosphorylated by kinases. Amino acid residues 176 and 181 which were defined as mutation sites in current study had high score performance value for different kinases presented by NetPhosK predictor. PFP algorithm searched conventional databases with relative probability of Gene Ontologies (GO) to predict the most probable GO annotations in three Biological Process (BP), Molecular Function (MF) and Cellular Component (CC) categories which is presented in Fig. 1 and Table 5. According to this prediction the feature of viral nucleocapsid with the highest score of 73709 in CC category related to the full length of core protein while the function of core protein in two other categories BP and MF limited to C-terminal domain.


The role of mutations in core protein of hepatitis B virus in liver fibrosis.

Mohamadkhani A, Jazii FR, Poustchi H, Nouraein O, Abbasi S, Sotoudeh M, Montazeri G - Virol. J. (2009)

Predicted GO annotations for HBV core protein sequence, The PFP algorithm scored GO terms individually and includes information from distantly related sequences to HBV core protein. The function of each GO has been shown in table 5.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2800847&req=5

Figure 1: Predicted GO annotations for HBV core protein sequence, The PFP algorithm scored GO terms individually and includes information from distantly related sequences to HBV core protein. The function of each GO has been shown in table 5.
Mentions: Core protein with the largest number of serine sites in C-terminal tail could be widely phosphorylated by kinases. Amino acid residues 176 and 181 which were defined as mutation sites in current study had high score performance value for different kinases presented by NetPhosK predictor. PFP algorithm searched conventional databases with relative probability of Gene Ontologies (GO) to predict the most probable GO annotations in three Biological Process (BP), Molecular Function (MF) and Cellular Component (CC) categories which is presented in Fig. 1 and Table 5. According to this prediction the feature of viral nucleocapsid with the highest score of 73709 in CC category related to the full length of core protein while the function of core protein in two other categories BP and MF limited to C-terminal domain.

Bottom Line: Mutations in CTL epitopes and in phosphorylation sites of C-terminal domain of core protein also were associated with higher liver fibrosis (P = 0.003 and P = 0.04; Fisher's exact test for both).Patients with mutations in B cell and T helper epitopes did not show significant difference in the clinical features.Our data suggests that core protein mutations in CTL epitopes and C-terminal domain accompanied with higher stage of liver fibrosis may be due to alterations in the function of core protein.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Institute of Genetic Engineering and Biotechnology Tehran, Iran. ashraf@ams.ac.ir

ABSTRACT
The core protein of hepatitis B virus encompasses B- and T-cell immunodominant epitopes and subdivided into two domains: the N-terminal and the functional C-terminal consisted phosphorylation sites. Mutations of the core gene may change the conformation of the core protein or cause alteration of important epitopes in the host immune response. In this study twenty nine men (mean age 40 +/- 9 years old) with chronic hepatitis B were recruited for direct sequencing of the core gene. Serum ALT and HBV DNA level were measured at the time of liver biopsy. The effects of core protein mutations on patients' characteristics and subsequently mutations in B cell, T helper and cytotoxic T lymphocyte (CTL) epitopes and also C-terminal domain of core protein on the activity of liver disease was evaluated. Liver fibrosis was significantly increased in patients with core protein mutation (1.0 +/- 0.8 vs 1.9 +/- 1.4 for mean stage of fibrosis P = 0.05). Mutations in CTL epitopes and in phosphorylation sites of C-terminal domain of core protein also were associated with higher liver fibrosis (P = 0.003 and P = 0.04; Fisher's exact test for both). Patients with mutation in C-terminal domain had higher serum ALT (62 +/- 17 vs 36 +/- 12 IU/l, p = 0.02). Patients with mutations in B cell and T helper epitopes did not show significant difference in the clinical features. Our data suggests that core protein mutations in CTL epitopes and C-terminal domain accompanied with higher stage of liver fibrosis may be due to alterations in the function of core protein.

Show MeSH
Related in: MedlinePlus