Rahbar Ramtin, Murooka Thomas T, Hinek Anna A, Galligan Carole L, Sassano Antonella, Yu Celeste, Srivastava Kishore, Platanias Leonidas C, Fish Eleanor N
Toronto General Research Institute, 67 College Street, Rm. 424, Toronto, Ontario M5G 2M1, Canada.
J Virol. 2006 Jul;80(14):7245-59. doi: 10.1128/JVI.00463-06.
Vaccinia virus, a poxvirus, produces structurally distinct forms of virions for which the immediate events following cell entry are ill-defined. We provide evidence that intracellular mature virus (IMV) enters both permissive and nonpermissive T-cell lines and that introduction of CCR5 into nonpermissive mouse fibroblasts or human primary T cells renders the cells permissive for vaccinia replication. Notably, T cells expressing CCR5 in which tyrosine 339 in the intracellular region is replaced by phenylalanine no longer support virus replication or virus-inducible activation of specific host cell signaling effectors IRS-2, Grb2, and Erk1/2. We show that following IMV entry into the cell, the intact but not the tyrosine-deficient CCR5 is rapidly internalized and colocalizes with virus. This colocalization precedes virus-inducible signaling and replication.
痘苗病毒是一种痘病毒，可产生结构不同的病毒粒子形式，而细胞进入后紧接着发生的事件尚不明确。我们提供的证据表明，细胞内成熟病毒（IMV）可进入允许性和非允许性T细胞系，并且将CCR5引入非允许性小鼠成纤维细胞或人原代T细胞可使这些细胞允许痘苗病毒复制。值得注意的是，在细胞内区域中酪氨酸339被苯丙氨酸取代的表达CCR5的T细胞不再支持病毒复制或病毒诱导的特定宿主细胞信号效应器IRS-2、Grb2和Erk1/2的激活。我们表明，IMV进入细胞后，完整的而非酪氨酸缺陷型的CCR5会迅速内化并与病毒共定位。这种共定位先于病毒诱导的信号传导和复制。
