The HSV-1 pUL37 protein promotes cell invasion by regulating the kinesin-1 motor

• 成果类型: Article
• 署名作者: Kim, Dongho; Cianfrocco, Michael A.; Verhey, Kristen J.; Smith, Gregory A.; Shenk, Thomas
• 署名单位: Northwestern University; Feinberg School of Medicine; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13481
• DOI: 10.1073/pnas.2401341121
• 发表日期: 2024-05-07
• 关键词: herpes-simplex-virus; pseudorabies virus; tegument protein; axonal-transport; capsid transport; nervous-system; dynein; phosphorylation; localization; infection

摘要

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.