The presence or absence of the gamma-activated site determines IFN gamma-mediated transcriptional activation in CAEV promoters cloned from the mammary gland and joint synovium of a single CAEV-infected goat

The caprine arthritis encephalitis virus (CAEV) long terminal repeat promoter was cloned and sequenced from mammary gland and carpal joint synovium isolated from a 15.5 year old, CAEV-infected Toggenburg doe with chronic mastitis and carpal arthritis. A deletion of the CAEV gamma activated site (GAS) was identified in the mammary gland but not the synovial isolate. Subsequent promoter-reporter gene construct experiments indicated that the GAS is necessary for interferon γ-mediated promoter activation. Utilizing a molecular clone of the classic isolate CAEV-CO, these findings were corroborated by a set of GAS mutant promoter–reporter constructs with and without the CAEV GAS. Results of experiments with U937 monocyte cell lines stably transfected with molecular clones of CAEV-CO GAS deletion mutants also indicated the GAS is necessary for IFNγ-mediated promoter activation. The mammary gland CAE viral isolate was propagated in caprine peripheral blood mononuclear cells and was assigned the name CAEV-MA. This is the first report describing two CAE viral isolates cloned from different anatomical locations in the same animal with and without the CAEV GAS, and is the first report detailing cytokine-induced CAEV promoter function in a naturally occurring ΔGAS promoter.

► The presence of the CAEV gamma activated site (GAS) is required for IFNγ-mediated promoter activation in naturally occurring CAEV promoter isolates with or without the CAEV GAS.
► CAE viral promoters lacking the GAS are rare, indicating the biological importance of this promoter motif.
► This ΔGAS CAEV lentivirus has been successfully propagated via mammary gland explant co-cultures in caprine peripheral blood mononuclear cells.