Precore/Core Promoter Mutant Hepatitis B Virus Produces More Severe Histologic Liver Disease than Wild Type Hepatitis B Virus

2007 ◽  
Vol 1 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Mamun-Al-Mahtab ◽  
Salimur Rahman ◽  
Mobin Khan ◽  
Ayub Mamun ◽  
Kamal
Keyword(s):  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Promoter ◽  
Wild Type ◽  
B Virus ◽  
Promoter Mutant

Reversion from precore/core promoter mutants to wild-type hepatitis B virus during the course of lamivudine therapy

2002 ◽  
Vol 36 ◽  
pp. 86
Author(s):  
Hikmet Akkiz ◽  
Yilmaz Ergun ◽  
Salih Colakoglu ◽  
Macit Sandikci ◽  
Mehmet Serin ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Promoter ◽  
Wild Type ◽  
Lamivudine Therapy ◽  
B Virus

scholarly journals Genome Replication, Virion Secretion, and e Antigen Expression of Naturally Occurring Hepatitis B Virus Core Promoter Mutants

2003 ◽  
Vol 77 (12) ◽  
pp. 6601-6612 ◽  
Author(s):  
Sameer Parekh ◽  
Fabien Zoulim ◽  
Sang Hoon Ahn ◽  
Adrienne Tsai ◽  
Jisu Li ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Genome ◽  
Core Promoter ◽  
Hepatoma Cell ◽  
Genome Replication ◽  
Wild Type ◽  
Naturally Occurring ◽  
B Virus ◽  
Promoter Mutations

ABSTRACT The core promoter mutants of hepatitis B virus (HBV) emerge as the dominant viral population at the late HBeAg and the anti-HBe stages of HBV infection, with the A1762T/G1764A substitutions as the hotspot mutations. The double core promoter mutations were found by many investigators to moderately enhance viral genome replication and reduce hepatitis B e antigen (HBeAg) expression. A much higher replication capacity was reported for a naturally occurring core promoter mutant implicated in the outbreak of fulminant hepatitis, which was caused by the neighboring C1766T/T1768A mutations instead. To systemically study the biological properties of naturally occurring core promoter mutants, we amplified full-length HBV genomes by PCR from sera of HBeAg+ individuals infected with genotype A. All 12 HBV genomes derived from highly viremic sera (5 × 109 to 5.7 × 109 copies of viral genome/ml) harbored wild-type core promoter sequence, whereas 37 of 43 clones from low-viremia samples (0.2 × 107 to 4.6 × 107 copies/ml) were core promoter mutants. Of the 11 wild-type genomes and 14 core promoter mutants analyzed by transfection experiments in human hepatoma cell lines, 6 core promoter mutants but none of the wild-type genomes replicated at high levels. All had 1762/1764 mutations and an additional substitution at position 1753 (T to C), at position 1766 (C to T), or both. Moreover, these HBV clones varied greatly in their ability to secrete enveloped viral particles irrespective of the presence of core promoter mutations. High-replication clones with 1762/1764/1766 or 1753/1762/1764/1766 mutations expressed very low levels of HBeAg, whereas high-replication clones with 1753/1762/1764 triple mutations expressed high levels of HBeAg. Experiments with site-directed mutants revealed that both 1762/1764/1766 and 1753/1762/1764/1766 mutations conferred significantly higher viral replication and lower HBeAg expression than 1762/1764 mutations alone, whereas the 1753/1762/1764 triple mutant displayed only mild reduction in HBeAg expression similar to the 1762/1764 mutant. Thus, core promoter mutations other than those at positions 1762 and 1764 can have major impact on viral DNA replication and HBeAg expression.

scholarly journals Effects of Hepatitis B Virus Mutations on its Replication and Liver Disease Severity

2013 ◽  
Vol 7 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Abdulrahim Hakami ◽  
Abdelwahid Ali ◽  
Ahmed Hakami
Keyword(s):  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Disease Severity ◽  
Chronic Infection ◽  
Core Promoter ◽  
Basal Core Promoter ◽  
Double Mutation ◽  
B Virus ◽  
Genotype C

Hepatitis B virus (HBV), nowadays, is one of the major human pathogens worldwide. Approximately, 400 million people worldwide have chronic HBV infection. Only 5% of persons infected during adulthood develop chronic infection. The reverse is true for those infected at birth or in early childhood, i.e. more than 90% of these persons progress to chronic infection. Currently, eight different genotypes o f HBV have been identified, differing in nucleotide sequence by greater than 8%. In addition, numerous subgenotypes have a l s o been recognized based on the nucleotide sequence variability of 4- 8%. It has invariably been found that these genotypes and mutations play a pivotal role in the liver disease aggravation and virus replication. The precore mutations (G1896A) and the double mutation (T1762/A1764) in the basal core promoter are important mutations that alter expression of the hepatitis B e antigen (HBeAg). The HBeAg is important for establishing viral persistence. The precore G1896A mutation abrogates the expression of HBeAg. Numerous other mutations alter the disease severity and progression. It is predictive that the infected patient has high risk of hepatocellular carcinoma if the genotype C is incriminated or if HBV possesses basal core promoter double mutation. Association of the remaining genotypes have been noted but with less degree than genotype C. Phenotypic assays of the different HBV protein markers with different molecular techniques illustrate the replication efficiency of the virus in cell lines. This review will discuss various mutations into their association with liver disease severity and progression as well as virus replication.

scholarly journals Specific mutations of basal core promoter are associated with chronic liver disease in hepatitis B virus subgenotype D1 prevalent in Turkey

2013 ◽  
Vol 57 (2) ◽  
pp. 122-129 ◽  
Author(s):  
Mustafa Sunbul ◽  
Masaya Sugiyama ◽  
Fuat Kurbanov ◽  
Hakan Leblebicioglu ◽  
Anis Khan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Liver Disease ◽  
Core Promoter ◽  
Chronic Liver ◽  
Basal Core Promoter ◽  
B Virus
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