title: TNFalpha and GM-CSF-induced activation of the CAEV promoter is independent of AP-1.
abstract: Caprine arthritis encephalitis virus transcription is under the control of the viral promoter within the long terminal repeat. Previous studies with the closely related maedi visna lentivirus have indicated that viral transcription is dependent upon the AP-1 transcription factor. Other studies have indicated a potential role for the cytokines TNFalpha and GM-CSF in CAEV pathogenesis by increasing viral loads in infected tissues. The hypotheses that AP-1 transcription factors are necessary for transcriptional activation of the CAEV promoter and that CAEV transcriptional activation results from treatment with the cytokines GM-CSF and TNFalpha were tested with a stably transduced U937 cell line. Here, we found that TNFalpha and GM-CSF activated CAEV transcription in U937 cells. However, this activation effect was not blocked by SP600125, an inhibitor of Jun N-terminal kinase. SP600125 effectively prevented Jun phosphorylation in cells subsequently treated with cytokines. The cytokines TNFalpha and GM-CSF therefore activate CAEV transcription, and this effect occurs independently of AP-1. A set of progressive deletion mutants was utilized to show that TNFalpha-induced expression depends on an element or elements within the U3 70-bp repeat.
authors.affiliation: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-0001, USA. bgm@vetmed.wsu.edu
authors.forename: Brian G
authors.initials: BG
authors.lastname: Murphy
authors.forename: Isidro
authors.initials: I
authors.lastname: Hötzel
authors.forename: Douglas P
authors.initials: DP
authors.lastname: Jasmer
authors.forename: William C
authors.initials: WC
authors.lastname: Davis
authors.forename: Donald
authors.initials: D
authors.lastname: Knowles
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D016088:Arthritis-Encephalitis Virus, Caprine / Q000235:genetics / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020298:U937 Cells
chemical_list: D000873:Anthracenes; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor