Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/15/2007
Publication Date: 3/26/2007
Citation: Murphy, B., Jasmer, D., White, S.N., Knowles Jr, D.P. 2007. Localization of a TNF-activated transcription site and interactions with the gamma activated site within the CAEV U3 70 base pair repeat. Virology. 364:196-207 Interpretive Summary: Control of persistent viral infections (those viruses which survive in the infected host for life) requires a detailed understanding of how viruses persist in the infected host and continue to replicate. These data show and two molecules which participate in inflammation, TNFa and IFNy also promote replication of caprine arthritis encephalitis virus. Additionally these data mapped the sites within the virus at which these molecules promote replication.
Technical Abstract: The cytokines TNF' and IFN' have previously been shown to activate caprine arthritis encephalitis virus (CAEV) transcription. Increased viral titers correlate with increased lesion severity. Therefore, TNF' and IFN' 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 TNF'-induced CAEV transcriptional activation. In contrast to the results of previous studies with IFN', we found that multiple sequences within the U3 region 70 bp repeat were required for IFN'-activation of the CAEV promoter. The results identify previously unrecognized complexity in the CAEV promoter that may be relevant to viral replication and disease.