Interferon (IFN)- 2 Genotype Analysis of Chinese Chronic Hepatitis B Patients Undergoing Recombinant IFN- 2a Therapy

Crowe, J.S.; Gewert, Dirk R.; Barber, Karen A.; Lewis, Alan P.; Sims, Martin; Davies, Sarah L.; Salom, Caroline; Wood, J C; Thomas, Howard; Thursz, Mark; Lok, Anna S.

doi:10.1093/infdis/169.4.875

Cited by 15 publications

(4 citation statements)

References 14 publications

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“…A few studies have investigated a possible association between genotype and fulminant hepatitis, or response to treatment with interferon [22,23]. To our knowledge, none has yet attempted to establish a link between genotype and risk of chronic outcome.…”

Section: Discussionmentioning

confidence: 99%

Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection?

Mayerat

Mantegani

Frei

1999

Journal of Viral Hepatitis

231

192

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Between 5 and 10% of adults infected with the hepatitis B virus (HBV) develop a chronic infection lasting longer than 6 months, which may lead to advanced liver disease. HBV can be classified into six genotypic families: A, B, C, D, E and F, but only genotypes A and D are significantly represented in western Europe, where they account for some 90% of cases of infection with HBV. In the present study, we investigated a possible association between HBV genotype A or D and clinical outcome of the infection. We compared the prevalence of these genotypes in a group of patients with chronic active hepatitis to that of a group with acute resolving hepatitis. In patients with chronic active hepatitis, genotype A was found in 28 of 35 patients and genotype D in only four. The remaining three patients were infected with genotype non-A, non-D. In contrast, genotype D was found in 24 of 30 patients with acute hepatitis, whilst genotype A was found in only three patients of this group. Three were infected with genotype non-A, non-D. Our results show a clear association between genotype A and chronic outcome (Ficher's exact test: two-sided P-value, P < 0.0001). They suggest that HBV genotypes may play a role in the virus-host relationship. Possible mechanisms for such a role are discussed.

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Section: Discussionmentioning

confidence: 99%

Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection?

Mayerat

Mantegani

Frei

1999

Journal of Viral Hepatitis

231

192

View full text Add to dashboard Cite

show abstract

“…This hypothesis is underscored by the observation that antibody production against rIFN␣-2a differs in ethnic groups, ie, 39% of Asian patients develop antibodies but only 14% of Caucasians. 19 A multicenter study accompanying a clinical trial of IFN␤-1a (Rebif ® ) therapy may contribute to unravel the genetic background predisposing for antibody production (C Hardt).…”

Section: Discussionmentioning

confidence: 99%

“…In fact, all individuals described so far (n = 75) are homozygous for the IFN␣-2b allele and induction of neutralizing antibodies is not surprising. 19 The clinical and immunological changes following IFN␤ therapy have been documented and numerous investigations were initiated in order to explain in vivo activities of IFN's by experimental systems in vitro. Since the function of a gene may be altered by mutations, polymorphism or sequence variations (MPSV) the present study was designed to determine the extent of polymorphism within the IFNB gene.…”

Section: Correspondence: Dr B Miterski Molecular Human Genetics Ruhmentioning

confidence: 99%

The interferon gene cluster: a candidate region for MS predisposition?

et al. 1999

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The clinical benefits of interferon (IFN) ␤ therapy in some multiple sclerosis (MS) patients are still unexplained, raising the question whether polymorphism within the IFNB gene itself would provide an explanation. Screening the IFNB gene by single strand conformation polymorphism (SSCP) analysis and sequencing, a single nucleotide polymorphism was identified. Both alleles were distributed with similar frequencies in MS patients and controls.

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“…IFN-␣, a human type I interferon (23), is used clinically as an anti-HBV drug (24,25), although the mechanism behind its antiviral effect is not yet fully understood. To investigate the possibility of whether the induction of ADAR1 suppresses HBV replication in IFN-␣-treated hepatocytes, loss-of-function of ADAR1 approaches were adopted.…”

Section: Endogenous Adar1 Negatively Regulates Hbv Rna Levelsmentioning

confidence: 99%

Adenosine deaminase acting on RNA-1 (ADAR1) inhibits hepatitis B virus (HBV) replication by enhancing microRNA-122 processing

Liu

Wang

et al. 2019

Journal of Biological Chemistry

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Edited by Charles E. Samuel Adenosine deaminases acting on RNA-1 (ADAR1) involves adenosine to inosine RNA editing and microRNA processing. ADAR1 is known to be involved in the replication of various viruses, including hepatitis C and D. However, the role of ADAR1 in hepatitis B virus (HBV) infection has not yet been elucidated. Here, for the first time, we demonstrated ADAR1 antiviral activity against HBV. ADAR1 has two splicing isoforms in human hepatocytes: constitutive p110 protein and interferon-␣ (IFN-␣)-responsive p150 protein. We found that overexpression of ADAR1 decreased HBV RNA in an HBV culture model. A catalytic-site mutant ADAR1 also decreased HBV RNA levels, whereas another adenosine deaminases that act on the RNA (ADAR) family protein, ADAR2, did not. Moreover, the induction of ADAR1 by stimulation with IFN-␣ also reduced HBV RNA levels. Decreases in endogenous ADAR1 expression by knock-down or knockout increased HBV RNA levels. A major hepatocyte-specific microRNA, miRNA-122, was found to be positively correlated with ADAR1 expression, and exogenous miRNA-122 decreased both HBV RNA and DNA, whereas, conversely, transfection with a miRNA-122 inhibitor increased them. The reduction of HBV RNA by ADAR1 expression was abrogated by p53 knock-down, suggesting the involvement of p53 in the ADAR1-mediated reduction of HBV RNA. This study demonstrated, for the first time, that ADAR1 plays an antiviral role against HBV infection by increasing the level of miRNA-122 in hepatocytes.

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Interferon (IFN)- 2 Genotype Analysis of Chinese Chronic Hepatitis B Patients Undergoing Recombinant IFN- 2a Therapy

Cited by 15 publications

References 14 publications

Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection?

Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection?

The interferon gene cluster: a candidate region for MS predisposition?

Adenosine deaminase acting on RNA-1 (ADAR1) inhibits hepatitis B virus (HBV) replication by enhancing microRNA-122 processing

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