The tyrosine phosphatase SHP-2 dephosphorylated by ALV-J via its Env efficiently promotes ALV-J replication

• Main Authors: Tuofan Li, Jing Xie, Xiaohui Yao, Jun Zhang, Chunping Li, Dan Ren, Luyuan Li, Quan Xie, Hongxia Shao, Aijian Qin, Jianqiang Ye
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2021-01-01
• Series: Virulence
• Subjects: alv-j; env; shp-2; phosphorylation; knockout; replication
• Online Access: http://dx.doi.org/10.1080/21505594.2021.1939952
• ISSN: 2150-5594; 2150-5608

Avian leukosis virus subgroup J (ALV-J) generally induces hemangioma, myeloid leukosis, and immunosuppression in chickens, causing significant poultry industry economic losses 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 fully understood. In this study, ALV-J infection and the overexpression of Env could efficiently downregulate the phosphorylation of SHP-2 (pSHP-2) in vitro and in vivo. The membrane-spanning domain (MSD) in Env Gp37 was the functional domain responsible for pSHP-2 downregulation. Moreover, 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, 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 Env could efficiently promote ALV-J replication, highlighting the important role of SHP-2 in the pathogenesis of ALV-J and providing a new target for developing antiviral drugs against ALV-J.