Localization of a TNF-activated transcription site and interactions with the gamma activated site within the CAEV U3 70 base pair repeat

Brian G Murphy, Douglas P. Jasmer, Stephen N. White, Donald Knowles

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The cytokines TNFα and IFNγ have previously been shown to activate caprine arthritis encephalitis virus (CAEV) transcription. Increased viral titers correlate with increased lesion severity. Therefore, TNFα and IFNγ may augment the caprine arthritis lesion by increasing viral titers. CAEV transcription is under the control of the viral promoter within the U3 region of the long terminal repeat. A set of U3 deletion mutants was generated and used to establish stably integrated, U937-based cell lines. These cell lines were utilized to define the required promoter sequences for cytokine-induced transcriptional activation. Here we have identified a novel 17 nucleotide TNF-activated site within the U3 region 70 bp repeat which is both required and sufficient in a minimal construct for TNFα-induced CAEV transcriptional activation. In contrast to the results of previous studies with IFNγ, we found that multiple sequences within the U3 region 70 bp repeat were required for IFNγ-activation of the CAEV promoter. The results identify previously unrecognized complexity in the CAEV promoter that may be relevant to viral replication and disease.

Original languageEnglish (US)
Pages (from-to)196-207
Number of pages12
JournalVirology
Volume364
Issue number1
DOIs
StatePublished - Jul 20 2007
Externally publishedYes

Keywords

  • CAEV
  • IFN gamma
  • LTR
  • SRLV promoter
  • TNF alpha

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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