Focal adhesion kinase is involved in rabies virus infection through its interaction with viral phosphoprotein P.

Baptiste Fouquet (1) , Jovan Nikolic (1) , Florence Larrous (2, 3) , Hervé Bourhy (3) , Christoph Wirblich (4) , Cécile Lagaudrière-Gesbert (1) , Danielle Blondel (1)

1 RHABDO - Rhabdovirus
2 CNR - Centre National de Référence de la Rage-Dynamique des Lyssavirus et adaptation à l'hôte
3 CC-OMS - Centre Collaborateur de l'OMS pour la Rage - Dynamique des lyssavirus et adaptation à l'hôte
4 Thomas Jefferson University, Philadelphia

The rabies virus (RABV) phosphoprotein P is a multifunctional protein: it plays an essential role in viral transcription and replication, and in addition, RABV P has been identified as an interferon antagonist. Here, a yeast two-hybrid screen revealed that RABV P interacts with the focal adhesion kinase (FAK). The binding involved the 106-to-131 domain, corresponding to the dimerization domain of P and the C-terminal domain of FAK containing the proline-rich domains PRR2 and PRR3. The P-FAK interaction was confirmed in infected cells by coimmunoprecipitation and colocalization of FAK with P in Negri bodies. By alanine scanning, we identified a single mutation in the P protein that abolishes this interaction. The mutant virus containing a substitution of Ala for Arg in position 109 in P (P.R109A), which did not interact with FAK, is affected at a posttranscriptional step involving protein synthesis and viral RNA replication. Furthermore, FAK depletion inhibited viral protein expression in infected cells. This provides the first evidence of an interaction of RABV with FAK that positively regulates infection. Rabies virus exhibits a small genome that encodes a limited number of viral proteins. To maintain efficient virus replication, some of them are multifunctional, such as the phosphoprotein P. We and others have shown that P establishes complex networks of interactions with host cell components. These interactions have revealed much about the role of P and about host-pathogen interactions in infected cells. Here, we identified another cellular partner of P, the focal adhesion kinase (FAK). Our data shed light on the implication of FAK in RABV infection and provide evidence that P-FAK interaction has a proviral function.

Domaines: Virologie

Baptiste Fouquet, Jovan Nikolic, Florence Larrous, Hervé Bourhy, Christoph Wirblich, et al.. Focal adhesion kinase is involved in rabies virus infection through its interaction with viral phosphoprotein P.. Journal of Virology, 2015, 89 (3), pp.1640-51. ⟨10.1128/JVI.02602-14⟩. ⟨pasteur-01430019⟩