Lara James, Purdy Michael A, Khudyakov Yury E
Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Infect Genet Evol. 2014 Jun;24:127-39. doi: 10.1016/j.meegid.2014.03.011. Epub 2014 Mar 22.
Hepatitis E virus (HEV) causes epidemic and sporadic cases of hepatitis worldwide. HEV genotypes 3 (HEV3) and 4 (HEV4) infect humans and animals, with swine being the primary reservoir. The relevance of HEV genetic diversity to host adaptation is poorly understood. We employed a Bayesian network (BN) analysis of HEV3 and HEV4 to detect epistatic connectivity among protein sites and its association with the host specificity in each genotype. The data imply coevolution among ∼70% of polymorphic sites from all HEV proteins and association of numerous coevolving sites with adaptation to swine or humans. BN models for individual proteins and domains of the nonstructural polyprotein detected the host origin of HEV strains with accuracy of 74-93% and 63-87%, respectively. These findings, taken together with lack of phylogenetic association to host, suggest that the HEV host specificity is a heritable and convergent phenotypic trait achievable through variety of genetic pathways (abundance), and explain a broad host range for HEV3 and HEV4.
戊型肝炎病毒（HEV）在全球引发了肝炎的流行和散发病例。HEV 基因型 3（HEV3）和 4（HEV4）可感染人类和动物，猪是主要储存宿主。人们对 HEV 遗传多样性与宿主适应性之间的相关性了解甚少。我们采用贝叶斯网络（BN）分析 HEV3 和 HEV4，以检测蛋白质位点之间的上位连接及其与各基因型宿主特异性的关联。数据表明，所有 HEV 蛋白中约 70%的多态性位点之间存在共同进化，且众多共同进化位点与适应猪或人类有关。非结构多蛋白的单个蛋白质和结构域的 BN 模型分别以 74% - 93%和 63% - 87%的准确率检测出 HEV 毒株的宿主来源。这些发现，再加上与宿主缺乏系统发育关联，表明 HEV 宿主特异性是一种可通过多种遗传途径实现的可遗传且趋同的表型特征，并解释了 HEV3 和 HEV4 的广泛宿主范围。
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