title: Kinesin-3 mediates axonal sorting and directional transport of alphaherpesvirus particles in neurons.
abstract: During infection of the nervous system, alphaherpesviruses-including pseudorabies virus (PRV)-use retrograde axonal transport to travel toward the neuronal cell body and anterograde transport to traffic back to the cell periphery upon reactivation from latency. The PRV protein Us9 plays an essential but unknown role in anterograde viral spread. To determine Us9 function, we identified viral and host proteins that interact with Us9 and explored the role of KIF1A, a microtubule-dependent kinesin-3 motor involved in axonal sorting and transport. Viral particles are cotransported with KIF1A in axons of primary rat superior cervical ganglion neurons, and overexpression or disruption of KIF1A function, respectively, increases and reduces anterograde capsid transport. Us9 and KIF1A interact early during infection with the aid of additional viral protein(s) but exhibit diminished binding at later stages, when capsids typically stall in axons. Thus, alphaherpesviruses repurpose the axonal transport and sorting pathway to spread within their hosts.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Tal
authors.initials: T
authors.lastname: Kramer
authors.forename: Todd M
authors.initials: TM
authors.lastname: Greco
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Taylor
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Ambrosini
authors.forename: Ileana M
authors.initials: IM
authors.lastname: Cristea
authors.forename: Lynn W
authors.initials: LW
authors.lastname: Enquist
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D011558:Herpesvirus 1, Suid / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D047908:Intracellular Signaling Peptides and Proteins; D016547:Kinesins / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D009474:Neurons / Q000821:virology*; D010750:Phosphoproteins / Q000378:metabolism*; D025941:Protein Interaction Mapping; D051381:Rats; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C490575:Kif1a protein, rat; D008074:Lipoproteins; D010750:Phosphoproteins; C491630:US9 protein, Suid herpesvirus 1; D014764:Viral Proteins; D016547:Kinesins