Rabies virus matrix protein interplay with eIF3, new insights into rabies virus pathogenesis.
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.
Komarova
Anastassia V
AV
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.
Real
Eléonore
E
Borman
Andrew M
AM
Brocard
Michèle
M
England
Patrick
P
Tordo
Noël
N
Hershey
John W B
JW
Kean
Katherine M
KM
Jacob
Yves
Y
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*
D039621:Eukaryotic Initiation Factor-3; D021122:Protein Subunits; D012333:RNA, Messenger; D012367:RNA, Viral; D014763:Viral Matrix Proteins