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Journal of Virology, November 2000, p. 10217-10222, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Cytoplasmic Dynein LC8 Interacts with Lyssavirus Phosphoprotein

Yves Jacob,1,* Hassan Badrane,1 Pierre-Emmanuel Ceccaldi,2 and Noël Tordo1

Laboratoire des Lyssavirus1 and Unité de la Rage,2 Institut Pasteur, 75724 Paris Cedex 15, France

Received 3 April 2000/Accepted 26 July 2000

Using a yeast two-hybrid human brain cDNA library screen, the cytoplasmic dynein light chain (LC8), a 10-kDa protein, was found to interact strongly with the phosphoprotein (P) of two lyssaviruses: rabies virus (genotype 1) and Mokola virus (genotype 3). The high degree of sequence divergence between these P proteins (only 46% amino acid identity) favors the hypothesis that this interaction is a common property shared by all lyssaviruses. The P protein-dynein LC8 interaction was confirmed by colocalization with laser confocal microscopy in infected cells and by coimmunoprecipitation. The dynein-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 cytoplasmic dynein and myosin V, which are involved in a wide range of intracellular motile events, such as microtubule minus-end directed organelle transport in axon "retrograde transport" and actin-based vesicle transport, respectively. Our results provide support for a model of viral nucleocapsid axoplasmic transport. Furthermore, the role of LC8 in cellular mechanisms other than transport, e.g., inhibition of neuronal nitric oxide synthase, suggests that the P protein interactions could be involved in physiopathological mechanisms of rabies virus-induced pathogenesis.


* Corresponding author. Mailing address: Laboratoire des Lyssavirus, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 33 (0) 1 45 68 87 53. Fax: 33 (0) 1 40 61 32 56. E-mail: yjacob{at}pasteur.fr.


Journal of Virology, November 2000, p. 10217-10222, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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