The tyrosine phosphatase SHP-2 dephosphorylated by ALV-J via its Env efficiently promotes ALV-J replication.
The tyrosine phosphatase SHP-2 dephosphorylated by ALV-J via its Env efficiently promotes ALV-J replication.
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DOI：
10.1080/21505594.2021.1939952
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发表时间：
2021-12
期刊：
影响因子：
5.2
通讯作者：
Ye J
中科院分区：
文献类型：
--
作者：
Li T;Xie J;Yao X;Zhang J;Li C;Ren D;Li L;Xie Q;Shao H;Qin A;Ye J
J亚群禽白血病病毒（ALV-J）可引起鸡的血管瘤、骨髓性白血病和免疫抑制，给世界范围内的养禽业造成巨大的经济损失。J型ALV-env基因与其它亚型ALV的同源性较低，与其独特的致病机制有关。然而，ALV-J的发病机制和肿瘤发生的确切分子基础仍不完全清楚。本研究中，ALV-J感染和Env的过表达可以在体内外有效地下调SHP-2（pSHP-2）的磷酸化。Env Gp 37中的跨膜结构域（MSD）是负责pSHP-2下调的功能结构域。SHP-2的过表达可有效促进ALV-J的复制，而敲除或抑制SHP-2则可抑制ALV-J的复制。此外，内源性鸡SHP-2基因敲除可显著提高DF-1细胞的增殖能力。这些结果表明，ALV-J Env脱磷酸化的SHP-2能够有效促进ALV-J的复制，提示SHP-2在ALV-J发病机制中的重要作用，为开发抗ALV-J的抗病毒药物提供了新的靶点。
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.
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影响因子：
9.4
作者：
Gao, Yulong;Yun, Bingling;Wang, Xiaomei
通讯作者：
Wang, Xiaomei
影响因子：
3.8
作者：
PAYNE, LN;BROWN, SR;THOULESS, ME
通讯作者：
THOULESS, ME
鸡肝细胞系可能通过其高水平病毒受体和高效蛋白质表达系统有效支持 ALV-J 的复制
影响因子：
4.4
作者：
Li T;Xie J;Lv L;Sun S;Dong X;Xie Q;Liang G;Xia C;Shao H;Qin A;Ye J
通讯作者：
Ye J
DOI：
10.1007/s00432-011-1143-5
发表时间：
2012-04-01
影响因子：
3.6
作者：
Jiang, Chengying;Hu, Fangke;Wei, Lixin
通讯作者：
Wei, Lixin
SHP2在发育障碍和肿瘤发生中的结构、功能和发病机制
影响因子：
3
作者：
Huang, Wen-Qing;Lin, Qing;Tzeng, Chi-Meng
通讯作者：
Tzeng, Chi-Meng