title: Rabies virus matrix protein interplay with eIF3, new insights into rabies virus pathogenesis.
abstract: Viral proteins are frequently multifunctional to accommodate the high density of information encoded in viral genomes. Matrix (M) protein of negative-stranded RNA viruses such as Rhabdoviridae is one such example. Its primary function is virus assembly/budding but it is also involved in the switch from viral transcription to replication and the concomitant down regulation of host gene expression. In this study we undertook a search for potential rabies virus (RV) M protein's cellular partners. In a yeast two-hybrid screen the eIF3h subunit was identified as an M-interacting cellular factor, and the interaction was validated by co-immunoprecipitation and surface plasmon resonance assays. Upon expression in mammalian cell cultures, RV M protein was localized in early small ribosomal subunit fractions. Further, M protein added in trans inhibited in vitro translation on mRNA encompassing classical (Kozak-like) 5'-UTRs. Interestingly, translation of hepatitis C virus IRES-containing mRNA, which recruits eIF3 via a different noncanonical mechanism, was unaffected. Together, the data suggest that, as a complement to its functions in virus assembly/budding and regulation of viral transcription, RV M protein plays a role in inhibiting translation in virus-infected cells through a protein-protein interaction with the cellular translation machinery.
authors.affiliation: Unité de la Régulation de la Traduction Eucaryote et Virale, CNRS URA 1966, Unité de Génétique Papillomavirus et Cancer Humain, Plate-forme de Biophysique des Macromolecules et de leurs interactions, Institute Pasteur, 75015 Paris, France.
authors.forename: Anastassia V
authors.initials: AV
authors.lastname: Komarova
authors.forename: Eléonore
authors.initials: E
authors.lastname: Real
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Borman
authors.forename: Michèle
authors.initials: M
authors.lastname: Brocard
authors.forename: Patrick
authors.initials: P
authors.lastname: England
authors.forename: Noël
authors.initials: N
authors.lastname: Tordo
authors.forename: John W B
authors.initials: JW
authors.lastname: Hershey
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Kean
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacob
mesh_terms: D000595:Amino Acid Sequence; D039621:Eukaryotic Initiation Factor-3 / Q000276:immunology / Q000378:metabolism*; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009154:Mutation; D014176:Protein Biosynthesis; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry; D012367:RNA, Viral / Q000737:chemistry; D011820:Rabies virus / Q000472:pathogenicity*; D012270:Ribosomes / Q000821:virology; D020349:Surface Plasmon Resonance; D020798:Two-Hybrid System Techniques; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D039621:Eukaryotic Initiation Factor-3; D021122:Protein Subunits; D012333:RNA, Messenger; D012367:RNA, Viral; D014763:Viral Matrix Proteins