Millar E L, Rennick L J, Weissbrich B, Schneider-Schaulies J, Duprex W P, Rima B K
Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Belfast, BT9 7BL Northern Ireland, UK.
Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Belfast, BT9 7BL Northern Ireland, UK; Department of Microbiology, Boston University School of Medicine and National Emerging Infectious Diseases Laboratories, Boston University, 620 Albany Street, Boston, MA 02118, United States.
Virus Res. 2016 Jan 4;211:29-37. doi: 10.1016/j.virusres.2015.09.016. Epub 2015 Sep 28.
Products expressed from the second (P/V/C) gene are important in replication and abrogating innate immune responses during acute measles virus (MV) infection. Thirteen clone sets were derived from the P/V/C genes of measles virus (MV) RNA extracted from brains of a unique collection of seven cases of subacute sclerosing panencephalitis (SSPE) caused by persistent MV in the central nervous system (CNS). Whether these functions are fully maintained when MV replicates in the CNS has not been previously determined. Co-transcriptional editing of the P mRNAs by non-template insertion of guanine (G) nucleotides, which generates mRNAs encoding the viral V protein, occurs much less frequently (9%) in the SSPE derived samples than during the acute infection (30-50%). Thus it is likely that less V protein, which is involved in combatting the innate immune response, is produced. The P genes in MV from SSPE cases were not altered by biased hypermutation but exhibited a high degree of variation within each case. Most but not all SSPE derived phospho-(P) proteins were functional in mini genome replication/transcription assays. An eight amino acid truncation of the carboxyl-terminus made the P protein non-functional while the insertion of an additional glycine residue by insertion of G nucleotides at the editing site had no effect on protein function.
由第二个(P/V/C)基因表达的产物在急性麻疹病毒(MV)感染期间的复制和消除先天性免疫反应中起重要作用。从因中枢神经系统(CNS)中持续性MV感染导致的7例亚急性硬化性全脑炎(SSPE)独特病例的大脑中提取的麻疹病毒(MV)RNA的P/V/C基因中获得了13个克隆集。此前尚未确定当MV在CNS中复制时这些功能是否能完全保持。通过鸟嘌呤(G)核苷酸的非模板插入对P mRNA进行共转录编辑,从而产生编码病毒V蛋白的mRNA,在源自SSPE的样本中发生的频率(9%)远低于急性感染期间(30 - 50%)。因此,可能产生的参与对抗先天性免疫反应的V蛋白较少。来自SSPE病例的MV中的P基因未因偏向性超突变而改变,但在每个病例中都表现出高度的变异性。在微型基因组复制/转录试验中,大多数(但不是全部)源自SSPE的磷酸化(P)蛋白具有功能。P蛋白羧基末端的8个氨基酸截短使其失去功能,而通过在编辑位点插入G核苷酸插入一个额外的甘氨酸残基对蛋白功能没有影响。