The Complete Nucleotide Sequence of a Pre-core Mutant of Hepatitis B Virus Implicated in Fulminant Hepatitis and Its Biological Characterization in Chimpanzees

Ogata, Norio; Miller, R.H.; Ishak, Kamal G.; Purcell, Robert H.

doi:10.1006/viro.1993.1257

Cited by 116 publications

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“…The e-antigen-negative HBVcontaining serum was previously used in chimpanzee and is known to induce more severe hepatitis. 25 However, it is difficult to exclude the possible presence of a small amount of e-antigen-producing virus that might help infection and replication of HBe antigen-negative HBV strain. Our results clearly demonstrate that HBV can infect and replicate in the complete absence of e-antigen-producing species.…”

Section: Discussionmentioning

confidence: 99%

Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis B virus

et al. 2005

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H epatitis B virus (HBV) is a small enveloped DNA virus and causes chronic infection of the liver that often leads to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. [1][2][3][4] The lack of a practical small animal model has impeded the study of the biology of this virus and the development of effective antiviral therapies. Chimpanzee is the only natural host that allows active replication of HBV. [5][6][7] Although this animal is a valuable model for the study of hepatitis viruses, 8 the practical use of chimpanzees is severely limited both ethically and economically.Several small animal models of HBV infection have been reported. The HBV transgenic mouse is a very useful model for the study of virology and evaluation of antiviral drugs. [9][10][11][12] However, the liver cells of this model are not permissive for HBV infection; therefore, studying virus-cell interactions such as receptor binding and entry is not possible. The HBVtrimera mouse is another useful mouse model. 13 In this model, ex vivo HBV-infected human liver fragments are implanted into lethally irradiated mice after SCID mouse bone marrow transplantation. Approximately 80% of the mice develop viremia 2 to 3 weeks after infection. However, the rate of positivity subsequently decreases to less than 20% 6 weeks after infection. The level viremia is approximately 10 5 copies/mL. More recently, HBV-containing human serum samples were used to infect human hepatocyte repopulated mice. 14 A high-level viremia (4.5 and 10 ϫ 10 8 copy/ mL) and HBs antigenemia are observed 8 weeks after injection. This mouse model is promising because HBV replicates in natural host cells, human hepatocytes. However,

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Section: Discussionmentioning

confidence: 99%

Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis B virus

et al. 2005

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“…The samples were tested for the presence of HBV DNA by PCR using conditions that have been described 32,37,38 with a nested primer set designed for the amplification of the gene encoding the a determinant of the HBV S protein. The nucleotide sequence of the primers was as follows: the outer sense primer was 5Ј-GAGAATTCAGAGTCTAGACTCGTG-GTGGACTT-3Ј, the outer antisense primer was 5Ј-TGAG-GATCCTACGAACCACTGAACAAATGGCAC-3Ј, the inner sense primer was 5Ј-CGCGAATTCTAGACTCGTGGTGGACTTCTCTCA-3Ј, and the inner antisense primer was 5Ј-CTAGGATCCACTGAA-CAAATGGCACTAGTAA-3Ј.…”

Section: Pcr Amplification and Nucleotide Sequence Analysis Of Hbv Dnamentioning

confidence: 99%

“…37 Direct nucleotide sequencing of the amplified DNA was performed by the dideoxy chain termination method as described previously. 32,37,38 Quantification and Subtyping of Anti-HBs Standard Assays. Serum samples collected from the 4 vaccinated chimpanzees at 3 weeks after the second vaccine dose and immediately before virus challenge were analyzed for anti-HBs titer and anti-HBs/a, d, and y subtype activities.…”

Section: Pcr Amplification and Nucleotide Sequence Analysis Of Hbv Dnamentioning

confidence: 99%

Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus

et al. 1999

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The emergence in vaccinated individuals of hepatitis B virus (HBV) mutants with amino acid substitutions within the a determinant of the surface protein has raised the possibility that such variants represent neutralization escape mutants. We previously demonstrated that one such mutant HBV, strain AS, with an arginine substituted for glycine at surface gene codon 145, was infectious and pathogenic in seronegative chimpanzees. In the present study, the protective efficacy of licensed hepatitis B vaccines was evaluated against challenge with this mutant virus.

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“…The absence of the 1896 mutation in this study could therefore be interpreted to indi-A-to-T base pair. 57 The silent G-to-A mutation at position 1888, which would also provide an additional A-T base pair cate a recent infection. However, HBV carriage in black Africans is predominantly acquired in childhood, 38 making this in the upper loop of the encapsidation signal (Fig.…”

Section: Aid Hepa 0046mentioning

confidence: 99%

Nucleic Acid Sequence Analysis of the Precore Region of Hepatitis B Virus From Sera of Southern African Black Adult Carriers of the Virus

et al. 1997

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an indicator of active viral replication and high levels of infecOur purpose was to ascertain if mutations of the pretivity. HBeAg negativity and hepatitis B e antigen antibody core region of the hepatitis B virus genome, in particular (anti-HBe) positivity are used as markers of decreased viral the 1896 stop codon mutation, are responsible for the replication and resolution of inflammation. 3 Precore muta-95% hepatitis B e antigen (HBeAg)-negativity rate in tions that abolish HBeAg expression without a concomitant southern African black adult carriers. Hepatitis B virus decrease in viral replication have, however, been described. (HBV) DNA was extracted from the serum of 57 asymp-A guanine (G) to adenine (A) transition at nucleotide 1896 of tomatic carriers (42 HBeAg-negative; 15 HBeAg-posithe precore region, resulting in a translational stop codon, is tive), the precore region was amplified using the polythe mutation that most often prevents HBeAg expression. 4,5 merase chain reaction (PCR), and sequenced. SixOther stop codon, translation-initiation codon, or frameshift carriers (14.6%) had mutations known to prevent HBeAg mutations are detected rarely. 5-9 synthesis: 4 involved the precore initiation codon (1814),The HBeAg-minus mutation caused by the 1896 transition and one created a stop codon at 1874. The 1896 mutation is present in almost all patients with anti-HBe-positive, occurred alone in one carrier only (2.4%). The infre-HBV DNA-positive chronic hepatitis in Italy, 8,10 Greece, 4 quency of the 1896 mutation can be explained by the Bulgaria, 11 Spain, 12 and Japan. 5 This mutation occurs less high prevalence (70%) of the adw subtype in the carriers frequently in North America, 13 France, 14-16 the United Kingstudied. Inter alia, adw differs from ayw in that codon dom, 17 and China. 18,19 is comprised of CCC instead of CCT. The presenceAlthough a few black Africans have been included in invesof C instead of T in position 1858 precludes the G-to-A tigations conducted in countries to which they have mimutation at 1896 because the coexistence of these two grated, 20-22 the prevalence of precore mutants of HBV in this mutations would destabilize the stem-loop structure of population has not been formally determined. the RNA encapsidation signal, a finding confirmed by HBV infection is hyperendemic in southern African blacks. our observation that the CCC polymorphism and the A feature of chronic carriers of HBV in this population is 1896 mutation were mutually exclusive. Ten HBeAg-negthat only 5% are still HBeAg-positive by the time they reach ative carriers (24%) had a missense mutation at position adulthood, 23 compared with higher rates of 40% or more in 1862 in the bulge of the RNA encapsidation signal, which other hyperendemic areas of the world. 24 The reason for the may possibly affect HBeAg expression by interfering high rate of HBeAg negativity is not known. Thus, the purwith either priming of reverse transcription or signal pose of this study was to determine whether mutations in peptide cleav...

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The Complete Nucleotide Sequence of a Pre-core Mutant of Hepatitis B Virus Implicated in Fulminant Hepatitis and Its Biological Characterization in Chimpanzees

Cited by 116 publications

References 0 publications

Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis B virus

Infection of human hepatocyte chimeric mouse with genetically engineered hepatitis B virus

Licensed recombinant hepatitis B vaccines protect chimpanzees against infection with the prototype surface gene mutant of hepatitis B virus

Nucleic Acid Sequence Analysis of the Precore Region of Hepatitis B Virus From Sera of Southern African Black Adult Carriers of the Virus

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