Herpesviruses assimilate kinesin to produce motorized viral particles

Caitlin E. Pegg, Sofia V. Zaichick, Ewa Bomba-Warczak, Vladimir Jovasevic, DongHo Kim, Himanshu Kharkwal, Duncan W. Wilson, Derek Walsh, Patricia J. Sollars, Gary E. Pickard, Jeffrey N. Savas and Gregory A. Smith ()
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Caitlin E. Pegg: Northwestern University Feinberg School of Medicine
Sofia V. Zaichick: Northwestern University Feinberg School of Medicine
Ewa Bomba-Warczak: Northwestern University Feinberg School of Medicine
Vladimir Jovasevic: Northwestern University Feinberg School of Medicine
DongHo Kim: Northwestern University Feinberg School of Medicine
Himanshu Kharkwal: Albert Einstein College of Medicine
Duncan W. Wilson: Albert Einstein College of Medicine
Derek Walsh: Northwestern University Feinberg School of Medicine
Patricia J. Sollars: University of Nebraska-Lincoln
Gary E. Pickard: University of Nebraska-Lincoln
Jeffrey N. Savas: Northwestern University Feinberg School of Medicine
Gregory A. Smith: Northwestern University Feinberg School of Medicine

Nature, 2021, vol. 599, issue 7886, 662-666

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-021-04106-w

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