@article{4e4230537e3144a1be12eb7e6cf23d99,
title = "Herpesviruses assimilate kinesin to produce motorized viral particles",
abstract = "Neurotropic alphaherpesviruses initiate infection in exposed mucosal tissues and, unlike most viruses, spread rapidly to sensory and autonomic nerves where life-long latency is established1. Recurrent infections arise sporadically from the peripheral nervous system throughout the life of the host, and invasion of the central nervous system may occur, with severe outcomes2. These viruses directly recruit cellular motors for transport along microtubules in nerve axons, but how the motors are manipulated to deliver the virus to neuronal nuclei is not understood. Here, using herpes simplex virus type I and pseudorabies virus as model alphaherpesviruses, we show that a cellular kinesin motor is captured by virions in epithelial cells, carried between cells, and subsequently used in neurons to traffic to nuclei. Viruses assembled in the absence of kinesin are not neuroinvasive. The findings explain a critical component of the alphaherpesvirus neuroinvasive mechanism and demonstrate that these viruses assimilate a cellular protein as an essential proviral structural component. This principle of viral assimilation may prove relevant to other virus families and offers new strategies to combat infection.",
author = "Pegg, {Caitlin E.} and Zaichick, {Sofia V.} and Ewa Bomba-Warczak and Vladimir Jovasevic and Kim, {Dong Ho} and Himanshu Kharkwal and Wilson, {Duncan W.} and Derek Walsh and Sollars, {Patricia J.} and Pickard, {Gary E.} and Savas, {Jeffrey N.} and Smith, {Gregory A.}",
note = "Funding Information: Acknowledgements We thank V. Gelfand and K. Verhey for suggestions that helped inform the experimental design and for reagents, and A. Roberts, M. Englke, M. Way, S. Brady and G. Gunderson for reagents. D. Kirchenbuechler of the Northwestern University Cell Imaging Facility, supported by NCI CCSG P30 CA060553, provided invaluable support in the development of the automated image analysis pipeline used in this report. Some confocal imaging was performed on an Andor XDI Revolution microscope purchased through the support of NCRR 1S10 RR031680-01 at the Northwestern University Cell Imaging Facility. Sequencing services were performed at the Northwestern University Genomics Core Facility. In vitro microtubule-dependent motility assays and analyses were performed in the Analytical Imaging Facility of the Albert Einstein College of Medicine, with support from National Cancer Institute cancer center grant P30CA013330. This work was funded by NIH AI056346 (G.A.S., P.J.S. and G.E.P.), AI125244 (D.W.W.), AI141470 (D.W.) and AI148780 (J.N.S.). E.B.W. was supported by NIH NS106812. C.E.P. received support from National Science Foundation DGE-1324585 and NIH Cellular and Molecular Basis of Disease Training Grant T32GM08061. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2021",
month = nov,
day = "25",
doi = "10.1038/s41586-021-04106-w",
language = "English (US)",
volume = "599",
pages = "662--666",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7886",
}