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细小病毒在疾病中的变异:与RNA病毒的差异?

Parvovirus variation for disease: a difference with RNA viruses?

作者信息

López-Bueno A, Villarreal L P, Almendral J M

机构信息

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, 28049 Cantoblanco, Madrid, Spain.

出版信息

Curr Top Microbiol Immunol. 2006;299:349-70. doi: 10.1007/3-540-26397-7_13.

DOI:10.1007/3-540-26397-7_13
PMID:16568906
Abstract

The Parvoviridae, a family of viruses with single-stranded DNA genomes widely spread from invertebrates to mammal and human hosts, display a remarkable evolutionary capacity uncommon in DNA genomes. Parvovirus populations show high genetic heterogeneity and large population sizes resembling the quasispecies found in RNA viruses. These viruses multiply in proliferating cells, causing acute, persistent or latent infections relying in the immunocompetence and developmental stage of the hosts. Some parvovirus populations in natural settings, such as carnivore autonomous parvoviruses or primate adeno associated virus, show a high degree of genetic heterogeneity. However, other parvoviruses such as the pathogenic B19 human erythrovirus or the porcine parvovirus, show little genetic variation, indicating different virus-host relationships. The Parvoviridae evolutionary potential in mammal infections has been modeled in the experimental system formed by the immunodeficient scid mouse infected by the minute virus of mice (MVM) under distinct immune and adaptive pressures. The sequence of viral genomes (close to 10(5) nucleotides) in emerging MVM pathogenic populations present in the organs of 26 mice showed consensus sequences not representing the complex distribution of viral clones and a high genetic heterogeneity (average mutation frequency 8.3 x 10(-4) substitutions/nt accumulated over 2-3 months). Specific amino acid changes, selected at a rate up to 1% in the capsid and in the NS2 nonstructural protein, endowed these viruses with new tropism and increased fitness. Further molecular analysis supported the notion that, in addition to immune pressures, the affinity of molecular interactions with cellular targets, as the Crml nuclear export receptor or the primary capsid receptor, as well as the adaptation to tissues enriched in proliferating cells, are major selective factors in the rapid parvovirus evolutionary dynamics.

摘要

细小病毒科是一类病毒,其单链DNA基因组广泛存在于从无脊椎动物到哺乳动物和人类宿主中,具有DNA基因组中罕见的显著进化能力。细小病毒群体表现出高度的遗传异质性和类似于RNA病毒中发现的准种的大群体规模。这些病毒在增殖细胞中繁殖,根据宿主的免疫能力和发育阶段引起急性、持续性或潜伏性感染。自然环境中的一些细小病毒群体,如食肉动物自主细小病毒或灵长类腺相关病毒,表现出高度的遗传异质性。然而,其他细小病毒,如致病性B19人红细胞病毒或猪细小病毒,表现出很少的遗传变异,表明不同的病毒-宿主关系。细小病毒科在哺乳动物感染中的进化潜力已在由免疫缺陷的scid小鼠在不同免疫和适应性压力下感染小鼠微小病毒(MVM)形成的实验系统中进行了模拟。在26只小鼠器官中出现的新兴MVM致病群体中的病毒基因组序列(接近10^5个核苷酸)显示,共有序列并不代表病毒克隆的复杂分布,且遗传异质性高(在2至3个月内积累的平均突变频率为8.3×10^-4个替换/核苷酸)。衣壳和NS2非结构蛋白中以高达1%的速率选择的特定氨基酸变化赋予这些病毒新的嗜性并提高了适应性。进一步的分子分析支持了这样一种观点,即除了免疫压力外,与细胞靶标的分子相互作用亲和力(如Crml核输出受体或主要衣壳受体)以及对富含增殖细胞的组织的适应性,是细小病毒快速进化动力学中的主要选择因素。

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