TY - JOUR
T1 - Kinesin-3 mediates axonal sorting and directional transport of alphaherpesvirus particles in neurons
AU - Kramer, Tal
AU - Greco, Todd M.
AU - Taylor, Matthew P.
AU - Ambrosini, Anthony E.
AU - Cristea, Ileana M.
AU - Enquist, Lynn William
N1 - Funding Information:
We thank K.J. Verhey, B. Vogelstein, S.J. Flint, and P. Ryan for generously providing reagents and R. Kratchmarov for assistance with virus construction. This work was supported by National Institutes of Health grants to L.W.E. (R37 NS33506, R01 NS060699, and P40 RR18604) and I.M.C. (DP1 DA026192), a Human Frontiers Science Program Organization award to I.M.C (RGY0079/2009-C), a National Science Foundation graduate research fellowship to T.K. (DGE-0646086), and an American Cancer Society postdoctoral research fellowship to M.P.T. (PF-1005701-MPC).
PY - 2012/12/13
Y1 - 2012/12/13
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chom.2012.10.013
DO - 10.1016/j.chom.2012.10.013
M3 - Article
C2 - 23245325
AN - SCOPUS:84871022299
SN - 1931-3128
VL - 12
SP - 806
EP - 814
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 6
ER -