Cytoplasmic dynein LC8 interacts with lyssavirus phosphoprotein

Using a yeast two-hybrid human brain cDNA library screen, the cytoplasmic d ynein light chain (LC8), a 10-kDa protein, was found to interact strongly w ith the phosphoprotein (P) of two lyssaviruses: rabies virus (genotype 1) a nd Mokola virus (genotype 3). The high degree of sequence divergence betwee n these P proteins (only 46% amino acid identity) favors the hypothesis tha t this interaction is a common property shared by all lyssaviruses. The P p rotein-dynein LC8 interaction was confirmed by colocalization with laser co nfocal microscopy in infected cells and by coimmunoprecipitation. The dynei n-interacting P protein domain was mapped to the 186 amino acid residues of the N-terminal half of the protein. Dynein LC8 is a component of both cyto plasmic dynein and myosin V, which are involved in a wide range of intracel lular motile events, such as microtubule minus-end directed organelle trans port in axon "retrograde transport" and actin-based vesicle transport, resp ectively. Our results provide support for a model of viral nucleocapsid axo plasmic transport. Furthermore, the role of LC8 in cellular mechanisms othe r than transport, e.g., inhibition of neuronal nitric oxide synthase, sugge sts that the P protein interactions could be involved in physiopathological mechanisms of rabies virus-induced pathogenesis.