PDF(Pubmed)
Abstract：
Neurotropic alphaherpesviruses, including herpes simplex virus type 1 (HSV-1), recruit microtubule motor proteins to invade cells. The incoming viral particle traffics to nuclei in a two-step process. First, the particle uses the dynein-dynactin motor to sustain transport to the centrosome. In neurons, this step is responsible for long-distance retrograde axonal transport and is an important component of the neuroinvasive property shared by these viruses. Second, a kinesin-dependent mechanism redirects the particle from the centrosome to the nucleus. We have reported that the kinesin motor used during the second step of invasion is assimilated into nascent virions during the previous round of infection. Here, we report that the HSV-1 pUL37 tegument protein suppresses the assimilated kinesin-1 motor during retrograde axonal transport. Region 2 (R2) of pUL37 was required for suppression and functioned independently of the autoinhibitory mechanism native to kinesin-1. Furthermore, the motor domain and proximal coiled coil of kinesin-1 were sufficient for HSV-1 assimilation, pUL37 suppression, and nuclear trafficking. pUL37 localized to the centrosome, the site of assimilated kinesin-1 activation during infection, when expressed in cells in the absence of other viral proteins; however, pUL37 did not suppress kinesin-1 in this context. These results indicate that the pUL37 tegument protein spatially and temporally regulates kinesin-1 via the amino-terminal motor region in the context of the incoming viral particle.
摘要：
嗜神经甲疱疹病毒，包括单纯疱疹病毒1型（HSV-1），招募微管运动蛋白侵入细胞。进入的病毒颗粒以两步的方式流向细胞核。首先,粒子使用动力蛋白-动力蛋白马达来维持向中心体的运输。在神经元中，这一步负责长距离逆行轴突运输，是这些病毒共有的神经侵入特性的重要组成部分。第二,驱动蛋白依赖机制将粒子从中心体重定向到细胞核。我们已经报道，在上一轮感染期间，在入侵的第二步中使用的驱动蛋白马达被吸收为新生的病毒体。这里,我们报告说，HSV-1pUL37外皮蛋白在逆行轴突运输过程中抑制同化的驱动蛋白-1运动。pUL37的区域2（R2）是抑制所必需的，并且独立于驱动蛋白1天然的自动抑制机制起作用。此外，驱动蛋白-1的运动区和近端卷曲螺旋足以同化HSV-1，pUL37抑制，核贩运。pUL37位于中心体，感染过程中同化驱动蛋白-1激活的部位，当在不存在其他病毒蛋白的细胞中表达时;然而，在这种情况下，pUL37不抑制驱动蛋白-1。这些结果表明，在进入的病毒颗粒的情况下，pUL37外皮蛋白通过氨基末端运动区在空间和时间上调节驱动蛋白1。
