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

Dong Ho Kim, Michael A. Cianfrocco, Kristen J. Verhey, Gregory A. Smith*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere2401341121
JournalProceedings of the National Academy of Sciences of the United States of America
Volume121
Issue number19
DOIs
StatePublished - May 7 2024

Keywords

  • axonal transport
  • centrosome
  • herpes simplex virus
  • HSV-1
  • kinesin

ASJC Scopus subject areas

  • General

Cite this