Microbiology and Molecular Genetics Graduate Program, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Virol. 2011 Jul;85(14):7402-10. doi: 10.1128/JVI.02391-10. Epub 2011 May 4.
After fusing with the plasma membrane, enveloped poxvirus virions form actin-filled membranous protrusions, called tails, beneath themselves and move toward adjacent uninfected cells. While much is known about the host and viral proteins that mediate formation of actin tails, much less is known about the factors controlling release. We found that the phosphoinositide 5-phosphatase SHIP2 localizes to actin tails. Localization requires phosphotyrosine, Abl and Src family tyrosine kinases, and neural Wiskott-Aldrich syndrome protein (N-WASP) but not the Arp2/Arp3 complex or actin. Cells lacking SHIP2 have normal actin tails but release more virus. Moreover, cells infected with viral strains with mutations in the release inhibitor A34 release more virus but recruit less SHIP2 to tails. Thus, the inhibitory effects of A34 on virus release are mediated by SHIP2. Together, these data suggest that SHIP2 and A34 may act as gatekeepers to regulate dissemination of poxviruses when environmental conditions are conducive.
与质膜融合后，有包膜的痘病毒病毒粒子在自身下方形成充满肌动蛋白的膜状突起，称为尾部，并向相邻的未感染细胞移动。尽管人们已经了解了介导肌动蛋白尾形成的宿主和病毒蛋白，但对控制释放的因素知之甚少。我们发现，磷酸肌醇 5-磷酸酶 SHIP2 定位于肌动蛋白尾部。定位需要磷酸酪氨酸、Abl 和 Src 家族酪氨酸激酶以及神经 Wiskott-Aldrich 综合征蛋白 (N-WASP)，但不需要 Arp2/Arp3 复合物或肌动蛋白。缺乏 SHIP2 的细胞具有正常的肌动蛋白尾部，但释放更多的病毒。此外，感染具有释放抑制剂 A34 突变的病毒株的细胞释放更多的病毒，但募集到尾部的 SHIP2 较少。因此，A34 对病毒释放的抑制作用是通过 SHIP2 介导的。总之，这些数据表明，SHIP2 和 A34 可能充当守门员，在环境条件有利时调节痘病毒的传播。
