TNFα and GM-CSF-induced activation of the CAEV promoter is independent of AP-1

Brian G Murphy, Isidro Hötzel, Douglas P. Jasmer, William C. Davis, Donald Knowles

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 TNFα 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 TNFα were tested with a stably transduced U937 cell line. Here, we found that TNFα 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 TNFα 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 TNFα-induced expression depends on an element or elements within the U3 70-bp repeat.

Original languageEnglish (US)
Pages (from-to)188-199
Number of pages12
JournalVirology
Volume352
Issue number1
DOIs
StatePublished - Aug 15 2006
Externally publishedYes

Fingerprint

Caprine Arthritis-Encephalitis Viruses
Transcription Factor AP-1
Granulocyte-Macrophage Colony-Stimulating Factor
Cytokines
U937 Cells
Transcriptional Activation
Progressive Interstitial Pneumonia of Sheep
Visna
Lentivirus
Terminal Repeat Sequences
Viral Load
Phosphotransferases
Phosphorylation
Cell Line

Keywords

  • AP-1
  • CAEV
  • GM-CSF
  • TNFα
  • Transcription

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

TNFα and GM-CSF-induced activation of the CAEV promoter is independent of AP-1. / Murphy, Brian G; Hötzel, Isidro; Jasmer, Douglas P.; Davis, William C.; Knowles, Donald.

In: Virology, Vol. 352, No. 1, 15.08.2006, p. 188-199.

Research output: Contribution to journalArticle

Murphy, Brian G ; Hötzel, Isidro ; Jasmer, Douglas P. ; Davis, William C. ; Knowles, Donald. / TNFα and GM-CSF-induced activation of the CAEV promoter is independent of AP-1. In: Virology. 2006 ; Vol. 352, No. 1. pp. 188-199.
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