Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NF kappa B binding domains of the Class I regulatory complex
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...
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| Format: | Article |
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2012
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| author | Othman, S. Abd Rahman, N. Yusof, R. |
| author_facet | Othman, S. Abd Rahman, N. Yusof, R. |
| author_sort | Othman, S. |
| collection | UM |
| description | 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 NF kappa B 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 kappa B1 and kappa B2 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. (C) 2011 Elsevier B.V. All rights reserved. |
| first_indexed | 2024-03-06T05:18:05Z |
| format | Article |
| id | um.eprints-7125 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T05:18:05Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | um.eprints-71252013-07-11T01:40:22Z http://eprints.um.edu.my/7125/ Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NF kappa B binding domains of the Class I regulatory complex Othman, S. Abd Rahman, N. Yusof, R. R Medicine 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 NF kappa B 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 kappa B1 and kappa B2 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. (C) 2011 Elsevier B.V. All rights reserved. 2012 Article PeerReviewed Othman, S. and Abd Rahman, N. and Yusof, R. (2012) Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NF kappa B binding domains of the Class I regulatory complex. Virus Research, 163 (1). pp. 238-245. ISSN 0168-1702, DOI https://doi.org/10.1016/j.virusres.2011.09.040 <https://doi.org/10.1016/j.virusres.2011.09.040>. 10.1016/j.virusres.2011.09.040 |
| spellingShingle | R Medicine Othman, S. Abd Rahman, N. Yusof, R. Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NF kappa B binding domains of the Class I regulatory complex |
| title | Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NF kappa B binding domains of the Class I regulatory complex |
| title_full | Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NF kappa B binding domains of the Class I regulatory complex |
| title_fullStr | Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NF kappa B binding domains of the Class I regulatory complex |
| title_full_unstemmed | Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NF kappa B binding domains of the Class I regulatory complex |
| title_short | Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NF kappa B binding domains of the Class I regulatory complex |
| title_sort | induction of mhc class i hla a2 promoter by dengue virus occurs at the nf kappa b binding domains of the class i regulatory complex |
| topic | R Medicine |
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