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Induction of the human gene for p44, a hepatitis-C-associated microtubular aggregate protein, by
A Kitamura1, K Takahashi, A Okajima
1Institute for Liver Research, Kansai Medical University, Osaka, Japan.
Abstract:
A hepatitis-C-associated microtubular aggregate protein, referred to as p44, has been identified as a cytoplasmic antigen in the hepatocytes of chimpanzees infected with hepatitis C virus. The production of p44 mRNA is markedly induced in the liver of chimpanzees infected with hepatitis C or hepatitis D virus. To examine the mechanism of this induction, we isolated a genomic clone for the human p44 protein and analyzed its structure. The human p44 gene spans approximately 14 kbp of DNA and consists of nine exons separated by eight introns. An interferon-stimulated response element, which confers inducibility by interferon-alpha/beta, was found in the promoter region of the gene. Northern-blot analysis revealed that the human p44 gene is inducible by interferon-alpha/beta, but not by interferon-gamma. Functional analysis demonstrated that the interferon-stimulated response element in the promoter region of the gene mediates the inducibility of the gene by interferon-alpha/beta. Thus, the human p44 gene is a member of the family of interferon-alpha/beta inducible genes. The protein p44 may be one of the mediators involved in the antiviral action of interferon.
Insights
Hepatitis C virus infection induces p44 protein production. The human p44 gene is interferon-alpha/beta inducible, suggesting p44 may play a role in the antiviral interferon response.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Hepatitis C virus (HCV) infection is associated with a protein called p44, found in chimpanzee liver cells.
- p44 mRNA production increases significantly in the liver during Hepatitis C virus (HCV) or Hepatitis D virus (HDV) infection.
Purpose of the Study:
- To investigate the mechanism behind the induction of p44 production.
- To analyze the structure of the human p44 gene and its regulatory elements.
Main Methods:
- Isolation and structural analysis of a human p44 gene genomic clone.
- Identification of regulatory elements within the gene's promoter region.
- Northern-blot analysis to assess gene inducibility by different types of interferon.
- Functional assays to confirm the role of identified response elements.
Main Results:
- The human p44 gene spans approximately 14 kbp and contains nine exons and eight introns.
- An interferon-stimulated response element (ISRE) was identified in the promoter region.
- The p44 gene is inducible by interferon-alpha/beta but not by interferon-gamma.
- The ISRE in the promoter region is responsible for mediating interferon-alpha/beta inducibility.
Conclusions:
- The human p44 gene is classified as an interferon-alpha/beta inducible gene.
- p44 protein is likely involved in mediating the antiviral effects of interferon.
- Understanding p44 regulation provides insights into host antiviral defense mechanisms against viral infections like HCV.