title: The role of oligomerization for the biological functions of the arenavirus nucleoprotein.
abstract: The Lassa virus nucleoprotein (NP) is a multifunctional protein that plays an essential role in many aspects of the viral life cycle, including RNA encapsidation, viral transcription and replication, recruitment of ribonucleoprotein complexes to viral budding sites, and inhibition of the host cell interferon response. While it is known that NP is capable of forming oligomers, both the oligomeric state of NP in mammalian cells and the significance of NP oligomerization for its various functions remain unclear. Here, we demonstrate that Lassa virus NP solely forms trimers upon expression in mammalian cells. Using a minigenome assay we show that mutants that are not able to form stable trimers are no longer functional during transcription and/or replication of the minigenome, indicating that NP trimerization is essential for transcription and/or replication of the viral genome. However, mutations leading to destabilization of the NP trimer did not impact the incorporation of NP into virus-like particles or its ability to suppress interferon-induced gene expression, two important functions of arenavirus NP.
authors.affiliation: Institute of Virology, Philipps University Marburg, Hans-Meerwein-Strasse 2, 35043, Marburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Lennartz
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoenen
authors.forename: Maria
authors.initials: M
authors.lastname: Lehmann
authors.forename: Allison
authors.initials: A
authors.lastname: Groseth
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Garten
mesh_terms: D000595:Amino Acid Sequence; D018050:Arenavirus / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D007836:Lassa virus / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D009698:Nucleoproteins; D014764:Viral Proteins