Extended Data Fig. 9: Model of viral assimilation of kinesin-1.

Neuroinvasive herpesviruses capture Kif5 (conventional kinesin; kinesin-1) into the tegument of newly formed virions during infection of epithelial cells. The captured epithelial kinesin-1 is carried between cells as a structural virion component and is deposited into cells (epithelia and neurons) upon the subsequent round of infection (first blue panel). Upon entry, cytosolic capsids engage in retrograde axonal transport effected by the cytoplasmic dynein/dynactin microtubule motor. The assimilated kinesin is presumably carried in an inactive state during this step of infection (second blue panel). Dynein/dynactin-based transport directs the capsid ‘minus-ended’ along microtubules ending at the centrosome, where the virus uses assimilated kinesin to transport to nuclei (third blue panel). When viruses are attenuated for assimilated-kinesin binding (e.g., PRV[RKB]) or are produced in the absence of Kif5, capsids predominately accumulate at the centrosome and do not progress toward the nucleus despite the presence of endogenous neuronal kinesin-1 (pink panel). Nevertheless, endogenous kinesin also supports nuclear trafficking of capsids.