Division of Microbiology and Infectious Diseases, Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Microbes Infect. 2010 Feb;12(2):135-45. doi: 10.1016/j.micinf.2009.11.002. Epub 2009 Nov 12.
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.
人偏肺病毒（HMPV）的 M2-2 蛋白由 M2 mRNA 内两个重叠开放阅读框之一编码。HMPV M2-2 蛋白的确切功能仍不清楚。我们使用小基因构建体和监测荧光素酶报告基因表达来检查 M2-2 蛋白对 HMPV 转录和复制的影响。小基因测定表明，M2-2 蛋白抑制转录和 RNA 复制。通过分别从其 N 端或 C 端去除 8 或 4 个氨基酸，M2-2 蛋白的抑制功能完全被消除，这表明两个短末端序列对于维持其功能结构都很重要。免疫沉淀实验表明 M2-2 蛋白与 L 蛋白相互作用，这可能参与了 HMPV 转录和复制的抑制。细胞内 M2-2 蛋白的预先积累严重限制了 HMPV 的复制。因此，感染细胞中固有病毒对 M2-2 基因表达的控制似乎对于 HMPV 的有效复制至关重要。
