Rôle des modulateurs de la protéine kinase D dans la propagation du virus herpès simplex de type 1
Herpes simplex virus type 1 affects the world's population by causing benign lesions such as cold sores, but also severe complications such as blindness. However, current treatments do not eradicate this virus, because the latter has a fast and complex life cycle. The molecular actors involved in the various stages of the viral cycle are still little known, but the laboratory has previously demonstrated the involvement of the host protein kinase D and diacylglycerol, its main anchoring molecule, in the release of the virus from the trans-Golgi network to the plasma membrane. This project goes further by studying the role of different modulators of protein kinase D in viral propagation. Following RNA interference, overexpression and drug experiments, the results demonstrate that, unlike protein kinase D, several of its modulators such as CERT, GGA1 and Nir2 negatively regulate the extracellular release of the virus. These effects are, moreover, independent of the total intracellular levels of diacylglycerol. Finally, electron microscopy suggests that protein kinase D and Nir2 do not only play a role in the trans-Golgi network, but also affect other steps of viral propagation such as nuclear release. These results contribute to a better understanding of the transport of herpes simplex virus type 1 and its interactions with the host cell. These new data could eventually lead to the development of new treatments, since they can be applied to other viruses or large cellular cargos.
CERT GGA Nir2 Transport intracellulaire Herpes simplex virus type 1 Trans-Golgi network Protein kinase D Intracellular transport