首页> 美国卫生研究院文献>Journal of Virology >Molecular Analysis of Three Ljungan Virus Isolates Reveals a New Close-to-Root Lineage of the Picornaviridae with a Cluster of Two Unrelated 2A Proteins
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Molecular Analysis of Three Ljungan Virus Isolates Reveals a New Close-to-Root Lineage of the Picornaviridae with a Cluster of Two Unrelated 2A Proteins

机译:三种Ljungan病毒分离物的分子分析揭示了具有两个不相关的2A蛋白簇的新近亲根系的Picornaviridae。

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摘要

Ljungan virus (LV) is a suspected human pathogen recently isolated from bank voles (Clethrionomys glareolus). In the present study, it is revealed through comparative sequence analysis that three newly determined Swedish LV genomes are closely related and possess a deviant picornavirus-like organization: 5′ untranslated region-VP0-VP3-VP1-2A1-2A2-2B-2C-3A-3B-3C-3D-3′ untranslated region. The LV genomes and the polyproteins encoded by them exhibit several exceptional features, such as the absence of a predicted maturation cleavage of VP0, a conserved sequence determinant in VP0 that is typically found in VP1 of other picornaviruses, and a cluster of two unrelated 2A proteins. The 2A1 protein is related to the 2A protein of cardio-, erbo-, tescho-, and aphthoviruses, and the 2A2 protein is related to the 2A protein of parechoviruses, kobuviruses, and avian encephalomyelitis virus. The unprecedented association of two structurally different 2A proteins is a feature never previously observed among picornaviruses and implies that their functions are not mutually exclusive. Secondary polyprotein processing of the LV polyprotein is mediated by proteinase 3C (3Cpro) possessing canonical affinity to Glu and Gln at the P1 position and small amino acid residues at the P1′ position. In addition, LV 3Cpro appears to have unique substrate specificity to Asn, Gln, and Asp and to bulky hydrophobic residues at the P2 and P4 positions, respectively. Phylogenetic analysis suggests that LVs form a separate division, which, together with the Parechovirus genus, has branched off the picornavirus tree most closely to its root. The presence of two 2A proteins indicates that some contemporary picornaviruses with a single 2A may have evolved from the ancestral multi-2A picornavirus.
机译:Ljungan病毒(LV)是最近从银行田鼠(Clethrionomys glareolus)中分离出来的可疑人类病原体。在本研究中,通过比较序列分析揭示了三个新确定的瑞典LV基因组密切相关,并拥有微小的微小RNA样组织:5'非翻译区-VP0-VP3-VP1-2A1-2A2-2B-2C- 3A-3B-3C-3D-3'非翻译区。 LV基因组和由其编码的多蛋白表现出一些特殊的功能,例如,没有预测的VP0成熟切割,在VP0中保守的序列决定簇(通常在其他小核糖核酸病毒的VP1中发现)以及两个不相关的2A蛋白簇。 2A1蛋白与心肺病毒,erbo病毒,tescho-病毒和气管病毒的2A蛋白有关,而2A2蛋白与副病毒,kobuviruses和禽脑脊髓炎病毒的2A蛋白有关。两种结构不同的2A蛋白之间空前的联系是小核糖核酸病毒以前从未观察到的特征,这表明它们的功能不是相互排斥的。左旋多蛋白的次级多蛋白加工是由蛋白酶3C(3C pro )介导的,该酶在P1位置具有对Glu和Gln的规范亲和力,在P1'位置具有小的氨基酸残基。此外,LV 3C pro 似乎对Asn,Gln和Asp以及分别对P2和P4位置的庞大疏水残基具有独特的底物特异性。系统发育分析表明,LVs形成了一个单独的分支,该分支与Parechovirus属一起从小核糖核酸病毒树的根部最紧密地分支出来。两个2A蛋白的存在表明某些具有单个2A的当代小核糖核酸病毒可能已经从祖先的多2A小核糖核酸病毒进化而来。

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