title: The interaction of flavivirus M protein with light chain Tctex-1 of human dynein plays a role in late stages of virus replication.
abstract: The role of the membrane protein (prM/M) in flavivirus life cycle remains unclear. Here, we identified a cellular interactor to the 40-residue-long ectodomain of prM/M (ectoM) using a yeast two-hybrid screen against a human cDNA library and GST pull-down assays. We showed that dynein light chain Tctex-1 interacts with the ectoM of dengue 1-4, West Nile, and Japanese encephalitis flaviviruses. No interaction was found with yellow fever and tick-borne flaviviruses. This interaction is highly specific since a single amino-acid change in the ectoM abrogates the interaction with Tctex-1. To understand the role of this interaction, silencing of Tctex-1 using siRNA was performed prior to infection. A significant decrease in progeny production was observed for dengue and West Nile viruses. Silencing Tctex-1 inhibited the production of recombinant dengue subviral particles (RSPs). Thus Tctex-1 may play a role in late stages of viral replication through its interaction with the membrane protein.
authors.affiliation: Unité des Interactions Moléculaires Flavivirus-Hôtes, Department of Virology, Institut Pasteur, 75724 Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Brault
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kudelko
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Vidalain
authors.forename: Frédéric
authors.initials: F
authors.lastname: Tangy
authors.forename: Philippe
authors.initials: P
authors.lastname: Desprès
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pardigon
mesh_terms: D003716:Dengue Virus / Q000502:physiology*; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D004664:Encephalitis Virus, Japanese / Q000502:physiology*; D020868:Gene Silencing; D054884:Host-Pathogen Interactions; D006801:Humans; D025941:Protein Interaction Mapping; D034741:RNA, Small Interfering / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014779:Virus Replication; D014902:West Nile virus / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D014759:Viral Envelope Proteins; C074932:prM protein, Flavivirus; D004398:Dyneins