The ability of the SIV mac239 vpr and vpx accessory genes to induce G2 phase arrest and apoptosis in the oncogenic process was tested. Primate lentivirus (HIV and SIV) vpr accessory genes encode 12-14 kDa proteins which induce specific cell cycle arrest at the G2 phase of infected cells preventing them from going through mitosis. Vpx is the second closely related protein encoded by the members of the HIV-2/SIVmac /SIVsmm group. Vpx and Vpr are critical for virus replication in non-dividing cells by participating in nuclear import of the pre-integration complex. Genomes of small ruminant lentiviruses: Caprine Arthritis Encephalitis Virus (CAEV) and Maedi Visna Virus (MVV), that are natural lentiviruses of domestic goat and sheep respectively, do not carry vpr and vpx genes. Thus, we developed a lentiviral chimeric virus based on the complete genome of CAEV in which the SIV mac239 vpr and vpx coding sequences were inserted. The resulting recombinant named CAEV-pBSCAvpxvpr was found to be infectious and replication competent. SIV Vpr/Vpx proteins were correctly and efficiently expressed in in vitro infected goat cells. Functional studies showed that SIV Vpr/Vpx proteins induce both specific G2 arrest of the cell cycle, and apoptosis in goat infected cells. Interestingly, following a high multiplicity of infection, both G2 arrest and apoptosis were found to be induced by Vpr/Vpx as early as 6 h post infection suggesting that the amount of SIV Vpr and Vpx proteins imported in the particles during the infection was sufficient to ensure such as functions. Data presented here highlight the evidence that proteins encoded by the accessory genes vpr and vpx govern two important functions (G2 arrest and apoptosis) which could be exploited as an appealing anti-cancer therapeutic approach that can be delivered with replication-defective CAEV vector.