Oncolytic viruses like measles virus, reovirus, adenovirus are promising alternatives in tumor treatment. Vesicular stomatitis virus(VSV) is a potent reagent for tumor virotherapy and has been tried in many types of tumor models. The selectivity of VSV replication in tumor cells has been regarded due to the defective of IFN signaling in tumor cells compared with normal cells. It has been reported that 80% of the tumor cells are typeⅠ IFN sinaling defective, which makes oncolytic VSV a promising method for tumor therapy. Recent analysis has demonstrated that defective control of mRNA translation initiation also plays a crucial role in cell permissiveness to VSV. Translation control downstream of PKR activation, frequently dysregulated in many transformed cells, can cooperate with attenuated IFN antiviral activity to facilitated VSV oncolysis. The problem with VSV oncolysis included that cleaning of viruses by host immune system, so the virus can not replicate effectively in tumors, the other is that the viruses can not spread effectively in the tumor tissue because of the tumor microenviroment, but one of the biggest problem is its safety. It was reported that when animals were injected with high dose of wild type VSV, neurotoxicity like hind limb paralysis occurred. There are kinds of strategies to improve safety for oncolytic viruses. Development of tumor antigen targeting VSV is an ideal alternative to improve safety and efficacy of the vector. Adult T cell leukemia (ATL) is a kind of human CD4 T cell tumor caused by HTLV-1, with phenotype of CD4+, CD3+, CD25+ and also CCR5+, CXCR4+. All of the present treatments only arrive partial success, which is underlying the urgency for new therapeutic drugs. Based on these rationales, it was hypothesized that the HIV gp160 pseudotyped VSV (VSV-ΔG-gp160G ) could be targeted at ATL cells, because entry of HIV-1 into human CD4 T cell depends on recognition of human CD4 and some co-receptors like CCR5 or CXCR4 and cause fusion between viral and cellular membranes. In the studies, with gp160 cytoplasmic tail replaced with that of VSV G, the HIV-1 envelope protein could be successfully incorporated into VSV. In one step replication curve, VSV-ΔG-gp160G can arrive at the highest titer at around 24 h post infection and the VSV-GFP titer did that at around 12 h post infection, and the titer of VSV-GFP was higher than that of VSV-gp160G, all these indicated that VSV-ΔG-gp160G has been attenuated after pseudotyping. To testify if VSV-ΔG-gp160G could kill ATL tumor cells efficiently, in particular, specifically. HTLV-1 transformed ATL tumor cells and non-ATL cells were infected with VSV-ΔG-gp160G or VSV-GFP for control respectively. The data indicated that the novel VSV could kill CD4 positive ATL cells selectively and potently, but not replicated in CD4 negative non ATL cells. This virus will be promising in treating adult T cell leukemia and lymphoma as well.