Expression of interferon-alpha receptor mRNA in the liver in chronic liver diseases associated with hepatitis C virus: Relation to effectiveness of interferon therapy

Fukuda, Ryo; Ishimura, Norihisa; Ishihara, Shunji; Tokuda, Alejandro; Satoh, Shuichi; Sakai, Shino; Akagi, Shuji; Watanabe, Makoto; Fukumoto, Shiro

doi:10.1007/bf02358606

Cited by 22 publications

(24 citation statements)

References 37 publications

(3 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…634,2000). Other studies have demonstrated that the IFN-␣/␤ receptor is down-regulated in HCV chronically infected patients (25,26,46). The importance of the host in IFN responsiveness was also demonstrated when the virus from an IFNunresponsive patient became responsive to IFN when transmitted to another individual (58).…”

Section: Resultsmentioning

confidence: 97%

DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus Infection

Bigger¹,

Brasky

Lanford³

2001

J Virol

415

344

View full text Add to dashboard Cite

Hepatitis C virus (HCV) poses a worldwide health problem in that the majority of individuals exposed to HCV become chronically infected and are predisposed for developing significant liver disease. DNA microarray technology provides an opportunity to survey transcription modulation in the context of an infectious disease and is a particularly attractive approach in characterizing HCV-host interactions, since the mechanisms underlying viral persistence and disease progression are not understood and are difficult to study. Here, we describe the changes in liver gene expression during the course of an acute-resolving HCV infection in a chimpanzee. Clearance of viremia in this animal occurred between weeks 6 and 8, while clearance of residual infected hepatocytes did not occur until 14 weeks postinfection. The most notable changes in gene expression occurred in numerous interferon response genes (including all three classical interferon antiviral pathways) that increased dramatically, some as early as day 2 postinfection. The data suggest a biphasic mechanism of viral clearance dependent on both the innate and adaptive immune responses and provide insight into the response of the liver to a hepatotropic viral infection.

show abstract

Section: Resultsmentioning

confidence: 97%

DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus Infection

Bigger¹,

Brasky

Lanford³

2001

J Virol

415

344

View full text Add to dashboard Cite

show abstract

“…Absent or low intrahepatic IFNARmRNA levels are related to a poor response to IFN-α, to increased histological hepatitis activity and to the severity of liver fibrosis in patients with chronic hepatitis C (10)(11)(12). In addition, IFNAR-mRNA expression in liver is correlated negatively with HCV-RNA viral load and the presence of HCV genotype 1b in HCV-infected patients (13)(14)(15).…”

mentioning

confidence: 85%

“…IFNAR1-mRNA has been detected in peripheral blood mononuclear cells (PBMC) from patients with chronic hepatitis C; however, no association with response to IFN-α was demonstrable (10). Using a semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we have analyzed IFNAR1-mRNA expression in PBMC from patients chronically infected with HCV and demonstrated its association with the IFN-α response.…”

mentioning

confidence: 99%

Interferon-alpha receptor 1 mRNA expression in peripheral blood mononuclear cells is associated with response to interferon-alpha therapy of patients with chronic hepatitis C

Massirer

Hirata

Silva

et al. 2004

Braz J Med Biol Res

View full text Add to dashboard Cite

Interferon (IFN)-α receptor mRNA expression in liver of patients with chronic hepatitis C has been shown to be a response to IFN-α therapy. The objective of the present study was to determine whether the expression of mRNA for subunit 1 of the IFN-α receptor (IFNAR1) in peripheral blood mononuclear cells (PBMC) is associated with the response to IFN-α in patients with chronic hepatitis C. Thirty patients with positive anti-HCV and HCV-RNA, and abnormal levels of alanine aminotransferase in serum were selected and treated with IFNα2b for one year. Those with HBV or HIV infection, or using alcohol were not included. Thirteen discontinued the treatment and were not evaluated. The IFN-α response was monitored on the basis of alanine aminotransferase level and positivity for HCV-RNA in serum. IFNAR1-mRNA expression in PBMC was measured by reverse transcriptionpolymerase chain reaction before and during the first three months of therapy. The results are reported as IFNAR1-mRNA/ß-actin-mRNA ratio (mean ± SD). Before treatment, responder patients had significantly higher IFNAR1-mRNA expression in PBMC (0.67 ± 0.15; N = 5; P < 0.05) compared to non-responders (0.35 ± 0.17; N = 12) and controls (0.30 ± 0.16; N = 9). Moreover, IFNAR1-mRNA levels were significantly reduced after 3 months of treatment in responders, whereas there were no differences in IFNAR1 expression in nonresponders during IFN-α therapy. Basal IFNAR1-mRNA expression was not correlated with the serum level of alanine and aspartate aminotransferases or the presence of cirrhosis. The present results suggest that IFNAR1-mRNA expression in PBMC is associated with IFN-α response to hepatitis C and may be useful for monitoring therapy in patients with chronic hepatitis C.

show abstract

“…It was reported that great apes could be infected with human hepatitis viruses, but usually do not progress to cirrhosis or hepatocellular carcinomas as often seen in human (31). Therefore, we would like to speculate a possibility of formulating a useful index for predicting the long-term efficacy of IFN therapy against chronic hepatitis C virus infection (32) on the confirmation of the functional consequence of the difference.…”

Section: Phylogeny Of Hominoid and Estimation Of Human͞pan Divergencementioning

confidence: 99%

Divergence of the genes on human chromosome 21 between human and other hominoids and variation of substitution rates among transcription units

Shi

Xi²,

Wang³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The study of genomic divergence between humans and primates may provide insight into the origins of human beings and the genetic basis of unique human traits and diseases. Chromosome 21 is the smallest chromosome in the human genome, and some of its regions have been implicated in mental retardation and other diseases. In this study, we sequenced the coding and regulatory regions of 127 known genes on human chromosome 21 in DNA samples from human and chimpanzees and a part of the corresponding genes from orangutan, gorilla, and macaque. Overall, 3,003 nucleotide differences between human and chimpanzee were identified over Ϸ400 kb. The differences in coding, promoter, and exon-intron junction regions were 0.51 ؎ 0.02%, 0.88 ؎ 0.03%, and 0.85 ؎ 0.02%, respectively, much lower than the previously reported 1.23% in genomic regions, which suggests the presence of purifying selection. Significant variation in substitution rate among genes was observed by comparing the divergence between human and chimpanzee. Furthermore, by implementing a bioinformatics-based approach, we showed that the identification of genetic variants specific to the human lineage might lead to an understanding of the mechanisms that are attributable to the phenotypes that unique to humans, by changing the structure and͞or dosage of the proteins expressed. A phylogenetic analysis unambiguously confirms the conclusion that chimpanzees were our closest relatives to the exclusion of other primates and the relative divergence of the Homo-Pan and that of (Homo-Pan)-Gorilla are 4.93 million years and 7.26 million years, respectively.

show abstract

Expression of interferon-alpha receptor mRNA in the liver in chronic liver diseases associated with hepatitis C virus: Relation to effectiveness of interferon therapy

Cited by 22 publications

References 37 publications

DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus Infection

DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus Infection

Interferon-alpha receptor 1 mRNA expression in peripheral blood mononuclear cells is associated with response to interferon-alpha therapy of patients with chronic hepatitis C

Divergence of the genes on human chromosome 21 between human and other hominoids and variation of substitution rates among transcription units

Contact Info

Product

Resources

About