PMID: 8970951Dec 1, 1996Paper

Type, prevalence, and significance of core promoter/enhancer II mutations in hepatitis B viruses from immunosuppressed patients with severe liver disease

Journal of Virology
S GüntherH Will

Abstract

Little is known about the functional significance of hepatitis B virus (HBV) sequence heterogeneity. Here we analyzed the type, frequency, and function of mutations in the core promoter/enhancer II region of HBV in immunosuppressed patients. The major HBV population in immunosuppressed patients with severe liver disease had deletions, insertions, and/or base changes in this region. Such mutations were not found in immunosuppressed patients with mild disease. Except for two mutations, all created a hepatocyte nuclear factor 1 (HNF1) binding site or a potential HNF3 binding site. Occasionally, known binding sites for C/EBP and HNF4 were additionally duplicated. Eleven mutated core promoter prototype sequences were functionally tested in the context of a wild-type genome by transfection in Huh7 cells. Despite the diversity of mutations tested, all decreased steady-state levels of pre-C mRNA drastically and increased those of the C mRNA/ pregenomic RNA. This correlated with reduced levels of secreted hepatitis B e antigen and increased intracellular levels of core and Pol proteins and replicative HBV DNA intermediates. The levels of secreted HBV DNA-containing particles were also increased although most of the mutations reduced the...Continue Reading

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Citations

Oct 31, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M SterneckH Will
Feb 5, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Petra PreikschatHelga Meisel
May 11, 2002·Journal of Cellular and Molecular Medicine·C Kreutz
Sep 13, 2002·Journal of Medical Virology·Talal A Sallam, C Y William Tong
Mar 21, 2003·Pediatric Research·Patrick GernerStefan Wirth
Oct 28, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·David Milich, T Jake Liang
May 25, 2005·Liver International : Official Journal of the International Association for the Study of the Liver·Irene CacciolaGiovanni Raimondo
Dec 5, 2018·BMC Microbiology·Kei FujiwaraShunsuke Nojiri
Oct 10, 1998·European Journal of Clinical Investigation·F Torre, N V Naoumov
Sep 10, 1999·Reviews in Medical Virology·S L NguiC G Teo
Oct 26, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y K ChunS S Kim
Feb 16, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·René GérolamiCatherine Tamalet
Jan 22, 2010·Journal of Virology·Hurng-Yi WangDing-Shinn Chen
Oct 9, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Mindie H Nguyen, Emmet B Keeffe
Feb 3, 2015·Transplant Infectious Disease : an Official Journal of the Transplantation Society·M ButiR Esteban
Oct 26, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·F SchlägerR Repp
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Jan 30, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Teresa PollicinoGiovanni Raimondo
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Jan 26, 2008·Emerging Infectious Diseases·Samir DervisevicRichard S Tedder
Feb 28, 2006·Journal of Virology·Philip MeulemanGeert Leroux-Roels
Jul 10, 2012·Virology Journal·Luciana BarbiniRodolfo Campos
Jun 13, 2012·Microbiology and Molecular Biology Reviews : MMBR·Esteban DomingoCelia Perales
Feb 2, 2011·Liver International : Official Journal of the International Association for the Study of the Liver·Iddo Bar-YishayAmir Shlomai
Sep 30, 2006·World Journal of Gastroenterology : WJG·Silke F FischerStephan Schaefer

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