HBZ is expressed by the complex retrovirus, Human T-cell Leukemia Virus type 1, and implicated in pathological effects associated with viral infection. From the nucleus, HBZ alters gene expression by interacting with a variety of transcriptional regulatory proteins, among which is c-Jun. Previously, one of the three HBZ variants, HBZ US , was reported to decrease c-Jun expression by promoting its degradation. Here we show that another variant, HBZ S1 , produces the opposite effect. In the presence of HBZ S1 , c-Jun expression increases due to its stabilization. Our data suggest that this effect requires the ability of HBZ S1 to interact with c-Jun. We provide evidence that HBZ S1 inhibits the proteosomal degradation of c-Jun initiated by the Cop1-containing ubiquitin ligase complex. HBZ S1 is the most abundant variant in HTLV-1-infected T-cells, and our data indicate that levels of c-Jun expression in infected cells are consistent with effects of HBZ S1. • The HBZ splice 1 variant (HBZ S1) increases the intracellular level of c-Jun. • HBZ S1 stabilizes c-Jun. • HBZ S1 decreases Cop1-dependent proteosomal degradation of c-Jun. [ABSTRACT FROM AUTHOR]