与其它亚群禽白血病病毒（ALV）不同，ALV-J主要引起造血细胞恶性增生、免疫抑制，诱导髓细胞瘤，血管瘤等。ALV-J独特囊膜蛋白Env被认为与其独特致病性相关，然其分子机理尚不清楚。我们发现，在ALV-JEnv中存在ITIM，YxxM以及类ITAM等免疫疾病、白血病发生相关免疫受体酪氨酸信号基序。那么，这些基序是否有功能？ALV-JEnv会不会与绵羊肺腺瘤及小鼠乳腺瘤反转录病毒Env一样具有转化致瘤功能呢？本项目拟对ALV-JEnv免疫受体酪氨酸信号通路进行研究：通过定点突变、传染性克隆构建、病毒拯救、细胞系构建、致病性试验等，检测Env磷酸化，与磷酸酶、激酶作用，转化表型，与ALV-J 致病致瘤关系。本项目的顺利开展，将揭示ALV-JEnv及其同源序列EAV-HP Env具有传递免疫受体酪氨酸信号通路的新功能，ALV-J致病致瘤新机理，并为开发抗ALV-J新药开拓思路，提供理论依据。

Different from other subgroups of avian leukosis virus (ALV), ALV-J causes hematopoietic malignancy and immune suppression, and mainly induces myeloid leukosis and hemangioma. The unique Env of ALV-J has been hypothesized to be related with its unique pathogenesis, but its molecular mechanism has not been clarified. Our previous studies found ITIM, YxxM and ITAM-like immunoreceptor tyrosine-based signal pathway motifs associated with immune disease and leukemogenesis are presented in the Env of ALV-J. Can the ALV-J Env conduct immunoreceptor tyrosine-based signal pathway through these motifs? Can the ALV-J Env do the same thing as the Env of Jaagsiekte sheep retrovirus and mouse mammary tumor virus, both showing oncogenesis? In this study, we plan to study on the immunoreceptor tyrosine-based signal pathway conducted by ALV-J Env. The phosphorylation of Env, interaction between Env and phosphatase or kinase, transformed phenotype of Env, and the relationship between Env and ALV-J pathogenesis will be tested and clarified in vitro and in vivo through PCR site mutagenesis, ALV-J infectious cloning, virus rescuing, stable cell line, pathogenesis et al. The results from this program will reveal the novel function of ALV-J Env and its high identity sequence EAV-HP Env for conducting immunoreceptor tyrosine-based signal pathway, discover new molecular mechanism for ALV-J pathogenesis, and pave the way for anti-viral treatment and drug development.