Zhang Jiaxin, Lei Xinnuo, Wang Dongliang, Jiang Yifan, Zhan Yang, Li Meng, Zhou Yawen, Qin Yiwen, Liu Jue, Wang Aibing, Yang Yi, Wang Naidong
The Key Laboratory of Animal Vaccine & Protein Engineering, College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China.
Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, No. 9 Shuguang Garden Middle Road, Haidian District, Beijing 100097, China.
Res Vet Sci. 2019 Jun;124:1-9. doi: 10.1016/j.rvsc.2019.01.024. Epub 2019 Jan 25.
Porcine circovirus type 2 (PCV2) causes huge economic losses in the global swine industry and has a complex and poorly understood virus-host interaction mechanism. We reported that the C-terminal of the capsid protein of all PCV2 isolates shared a strictly conserved PXXP motif that may interact with SH3 domain-containing tyrosine kinases; however, its roles in PCV2 cell entry and replication remain unknown. In this study, we determined that mRNA levels of two SH3 domain-containing tyrosine kinases family (Abl and Src) had distinct profiles (wild-type and PXXP-mutated) during PCV2 infections of PK15 cells. Therefore, we hypothesized that activities of tyrosine kinases (Abl and Fyn) in PK15 cells may be hijacked by PCV2 via its PXXP motif of the Cap, to favor virus replication. Specific inhibitors PP2 of Lck/Fyn and STI-571 of Abl family kinases decreased viral production through suppression of DNA and Cap synthesis at the replication stage. However, based on indirect immunofluorescence assay (IFA), entry of PCV2 virus-like particles (VLPs) into PK15 cells was not altered. Elucidating mechanisms of PCV2-host interactions should provide new insights for development of new compounds to prevent or reduce PCV2 infections.
猪圆环病毒2型（PCV2）给全球养猪业造成了巨大经济损失，其病毒-宿主相互作用机制复杂且尚未得到充分了解。我们报道，所有PCV2分离株的衣壳蛋白C末端都有一个严格保守的PXXP基序，该基序可能与含SH3结构域的酪氨酸激酶相互作用；然而，其在PCV2细胞进入和复制中的作用仍不清楚。在本研究中，我们确定在PK15细胞感染PCV2期间，两个含SH3结构域的酪氨酸激酶家族（Abl和Src）的mRNA水平具有不同的特征（野生型和PXXP突变型）。因此，我们推测PK15细胞中酪氨酸激酶（Abl和Fyn）的活性可能被PCV2通过其衣壳的PXXP基序劫持，以利于病毒复制。Lck/Fyn的特异性抑制剂PP2和Abl家族激酶的STI-571通过在复制阶段抑制DNA和衣壳合成来降低病毒产量。然而，基于间接免疫荧光分析（IFA），PCV2病毒样颗粒（VLP）进入PK15细胞的过程没有改变。阐明PCV2-宿主相互作用的机制应该为开发预防或减少PCV2感染的新化合物提供新的见解。
