| Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NFκB binding domains of the Class I Regulatory Complex. | |
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MedLine Citation:
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PMID: 22001567 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Despite aggressive efforts in dengue research, the control of dengue diseases and discovery of therapeutics against them await complete elucidation of its complex immune-pathogenesis. Unlike many viruses that escape the host's immune responses by suppressing the major histocompatibility complex (MHC) Class I pathway, many Flaviviruses up-regulate the cell surface expression of MHC Class I complex. We recently reported MHC Class I HLA-A2 promoter activation by all serotypes of dengue virus (DV). The mechanism by which DV regulates this is further explored here in HepG2 human liver cell line. Using real-time PCR, evidence that, similar to infections by other Flaviviruses, DV infection has the ability to up-regulate the MHC Class I transcription and mRNA synthesis, is presented. The region responsive towards DV infection of all serotypes was mapped to the Class I Regulatory Complex (CRC) of the HLA-A2 promoter. Competition electrophoretic mobility shift assay (EMSA) with NFκB probe established the presence of specific DNA-protein complex in DV-infected nuclear extracts. Antibody-supershift assays identified the MHC Class I promoter activation by DV to occur through binding of p65/p50 heterodimers and p65 homodimers to κB1 and κB2 cis-acting elements, respectively, within the CRC, and not with the interferon consensus sequence (ICS). This study presents evidence of MHC Class I gene modulation by DV, hence providing a better understanding of dengue immune-pathogenesis that would consequently facilitate the discovery of antiviral therapeutics against dengue. |
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Authors:
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Shatrah Othman; Noorsaadah Abd Rahman; Rohana Yusof |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-6 |
Journal Detail:
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Title: Virus research Volume: - ISSN: 1872-7492 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8410979 Medline TA: Virus Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
Affiliation:
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Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; Drug Design and Development Research Group, University of Malaya, 50603 Kuala Lumpur, Malaysia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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