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http://hdl.handle.net/11375/28747
Title: | Defibrinated bovine plasma inhibits retroviral transcription by blocking p52 activation of the NFkappaB element in the long terminal repeat. |
Authors: | van den Heuvel MJ Copeland KF Cates EC Jefferson BJ Jacobs RM |
Department: | Pathology & Molecular Medicine |
Keywords: | 3009 Veterinary Sciences;30 Agricultural, Veterinary and Food Sciences;Genetics;Cancer;Hematology;Infection;Animals;Antigens, Neoplasm;Cattle;Cells, Cultured;Chloramphenicol O-Acetyltransferase;Female;Gene Expression Regulation, Viral;Leukemia Virus, Bovine;NF-kappa B;Plasma;Terminal Repeat Sequences;Transcription, Genetic;Transfection;Virus Latency |
Publication Date: | Apr-2007 |
Publisher: | CANADIAN VET MED ASSOC |
Abstract: | Bovine leukemia virus (BLV) induces a persistent but latent infection in cattle. Viral latency is invoked by a protein known as plasma blocking factor (PBF) that is found in both bovine and human plasma. We report here on pathways that mediate latency in the presence of PBF. Reporter-gene constructs driven by the promoters of 6 retroviruses were used to measure the production of chloramphenicol acetyl transferase (CAT) in cell lines cultured with or without defibrinated bovine plasma. Plasma inhibited CAT production only in constructs containing an NFκB-binding element proximal to the initiation site (BLV, human immunodeficiency virus, and human T-cell leukemia virus). The promoters of Bovine immunodeficiency virus, Feline immunodeficiency virus, or Feline leukemia virus were not inhibited in the presence of bovine plasma. Using gel mobility shift assays, we demonstrated that activation of viral transcription upon stimulation with phorbol esters and ionomycin was mediated through the NFκB element and that this was abrogated in the presence of plasma. Furthermore, analysis of individual NFκB proteins in nuclear extracts of mononuclear cells or Jurkat cells showed that all 5 members of the NFκB family were upregulated in response to stimulation, but only p52 was significantly downregulated in the presence of bovine plasma. Thus, we infer that plasma effects are mediated through interference with either p52 translocation to the nucleus or p52 synthesis. |
URI: | http://hdl.handle.net/11375/28747 |
metadata.dc.identifier.doi: | https://doi.org/ |
ISSN: | 0830-9000 1928-9022 |
Appears in Collections: | Pathology & Molecular Medicine Publications |
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Defibrinated bovine plasma inhibits retroviral transcription by blocking p52 activation of the NFkappaB element in the long .pdf | 925.26 kB | Adobe PDF | View/Open |
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