title: Human metapneumovirus M2-2 protein inhibits viral transcription and replication.
abstract: M2-2 protein of human metapneumovirus (HMPV) is encoded by one of two overlapping open reading frames within M2 mRNA. The precise function of HMPV M2-2 protein remains unknown. We here examined effect of M2-2 protein on HMPV transcription and replication using a minigenome construct and monitoring luciferase reporter gene expression. The minigenome assays demonstrated that M2-2 protein inhibited both transcription and RNA replication. The inhibitory function of M2-2 protein was completely abrogated by removal of eight or four amino acids from its N- or C-terminus, respectively, demonstrating importance of both short terminal sequences for maintaining its functional structure. Immunoprecipitation experiments revealed interaction of M2-2 protein with L protein, which might be involved in inhibition of HMPV transcription and replication. Prior accumulation of intracellular M2-2 protein severely restrained HMPV from replicating. Thus inherent viral control of the M2-2 gene expression in infected cells seems to be essential for efficient HMPV replication.
authors.affiliation: Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.forename: Mayu
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Komatsu
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Masae
authors.initials: M
authors.lastname: Itoh
authors.forename: Bin
authors.initials: B
authors.lastname: Gotoh
mesh_terms: D001681:Biological Assay; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D006801:Humans; D029121:Metapneumovirus / Q000235:genetics* / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics*
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D012367:RNA, Viral; D014764:Viral Proteins