Activation of caprine arthritis-encephalitis virus long terminal repeat by gamma interferon

Abstract

Caprine arthritis-encephalitis virus (CAEV) is a lymphotropic lentivirus whose replication increases during monocyte maturation. We examined gene expression directed by the CAEV long terminal repeat (LTR) in a promonocytic cell line stimulated with several agents. Our results demonstrate that the CAEV LTR is activated by treatment of immature monocytes with gamma interferon (IFN-gamma) or a phorbol ester but not with tumor necrosis factor alpha or lipopolysaccharide. The cis-acting element in the LTR for the IFN-gamma response localizes to a duplicated 70-bp motif that contains an IFN-gamma response element, the gamma-activated site. One copy of the motif is necessary and sufficient for the response to IFN-gamma. Multiple copies contribute to basal transcriptional activity in the context of a heterologous promoter. This IFN-gamma response element in the CAEV LTR differs from the element required for the response to phorbol esters. Thus, activation of the CAEV LTR in monocytes that are stimulated by IFN-gamma, a cytokine that is secreted in response to viral infections, could contribute to conversion from latent to high-level viral replication in infected hosts.