The Tyrosine Phosphatase SHP-2 Dephosphorylated by ALV-J via its Env Eficiently Promotes ALV-J Replication

【作者】 李拓凡； Jing Xie； Xiaohui Yao； Jun Zhang； Chunping Li； Dan Ren； Luyuan Li； Quan Xie； Hongxia Shao； 秦爱建； 叶建强；

【Author】 Tuofan Li;Jing Xie;Xiaohui Yao;Jun Zhang;Chunping Li;Dan Ren;Luyuan Li;Quan Xie;Hongxia Shao;Aijian Qin;Jianqiang Ye;Key Laboratory of Jiangsu Preventive Veterinary Medicine,Key Laboratory for Avian Preventive Medicine,Ministry of Education,College of Veterinary Medicine,Yangzhou University;

【机构】 Key Laboratory of Jiangsu Preventive Veterinary Medicine,Key Laboratory for Avian Preventive Medicine,Ministry of Education,College of Veterinary Medicine,Yangzhou University；

【摘要】 Avian leukosis virus subgroup J(ALV-J) generally induces hemangioma,myeloid leukosis and immunosuppression in chicken,which has caused significant economic losses to the poultry industry worldwide.The unusual env gene of ALV-J,with low homology to other subgroups of ALVs,is associated with its unique pathogenesis.However,the exact molecular basis for the pathogenesis and oncogenesis of ALV-J is still not clear.In this study,we found ALV-J infection and the over-expression of its Env could efficiently downregulate the phosphorylation of SHP-2(pSHP-2)in intro and in vivo.Further study revealed that the Membrane-spanning domain(MSD) inGp37 of Env was the functional domain for decreasing thepSHP-2.Notably,the overexpression of SHP-2 could effectively promote the replication of ALV-J,whereas knockout or allosteric inhibition of SHP-2 could inhibit ALV-J replication.In addition,we found the knockout of endogenous chicken SHP-2 could significantly increase the proliferation ability of DF-1 cells.All these data demonstrate that SHP-2 dephosphorylated by ALV-J via its Env can efficiently promote ALV-J replication,highlighting the important role of SHP-2 in the pathogenesis of ALV-J and providing new target for developing anti-virus drug against ALV-J.更多还原

【Abstract】 Avian leukosis virus subgroup J(ALV-J) generally induces hemangioma,myeloid leukosis and immunosuppression in chicken,which has caused significant economic losses to the poultry industry worldwide.The unusual env gene of ALV-J,with low homology to other subgroups of ALVs,is associated with its unique pathogenesis.However,the exact molecular basis for the pathogenesis and oncogenesis of ALV-J is still not clear.In this study,we found ALV-J infection and the over-expression of its Env could efficiently downregulate the phosphorylation of SHP-2(pSHP-2)in intro and in vivo.Further study revealed that the Membrane-spanning domain(MSD) inGp37 of Env was the functional domain for decreasing thepSHP-2.Notably,the overexpression of SHP-2 could effectively promote the replication of ALV-J,whereas knockout or allosteric inhibition of SHP-2 could inhibit ALV-J replication.In addition,we found the knockout of endogenous chicken SHP-2 could significantly increase the proliferation ability of DF-1 cells.All these data demonstrate that SHP-2 dephosphorylated by ALV-J via its Env can efficiently promote ALV-J replication,highlighting the important role of SHP-2 in the pathogenesis of ALV-J and providing new target for developing anti-virus drug against ALV-J.更多还原