Evolution of the hepatitis E virus hypervariable region.
Evolution of the hepatitis E virus hypervariable region.
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DOI：
10.1099/vir.0.045351-0
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Simmonds P
中科院分区：
文献类型：
--
作者：
Smith DB;Vanek J;Ramalingam S;Johannessen I;Templeton K;Simmonds P
戊型肝炎病毒（HEV）基因组中高变区（HVR）的存在仍然无法解释。先前的研究已经将HVR描述为ORF 1多蛋白的侧翼功能结构域之间的富含脯氨酸的间隔区。其他人则认为该区域没有功能，它反映了病毒基因组的一个超变区域，它来自宿主序列的插入和进化，或者它受到正选择。本研究试图通过记录HVR内发生的进化过程来区分这些解释。我们已经测量了急性感染个体内或来自流行病学相关样品的序列之间的HVR序列的多样性，并且令人惊讶地发现这些数据集之间的相对同质性。我们没有发现HVR中氨基酸取代的正选择的证据。通过对已发表序列的分析，我们得出结论，在病毒基因型内观察到的HVR多样性的范围可以通过取代的积累来解释，并且在更小的程度上，通过该区域的缺失或重复来解释。所有已发表的HVR氨基酸序列显示脯氨酸和丝氨酸残基的相对过量，这不能通过基因组的这一部分中对胞嘧啶的局部偏好来解释。尽管所有已发表的HVR都含有一个或多个SH3结合PxxP基序，但该基序的出现频率并不比从这些序列中脯氨酸残基的比例所预期的更高。总之，这些观察结果与HVR具有依赖于长度和氨基酸组成而不是特定序列的结构作用的假设一致。
The presence of a hypervariable (HVR) region within the genome of hepatitis E virus (HEV) remains unexplained. Previous studies have described the HVR as a proline-rich spacer between flanking functional domains of the ORF1 polyprotein. Others have proposed that the region has no function, that it reflects a hypermutable region of the virus genome, that it is derived from the insertion and evolution of host sequences or that it is subject to positive selection. This study attempts to differentiate between these explanations by documenting the evolutionary processes occurring within the HVR. We have measured the diversity of HVR sequences within acutely infected individuals or amongst sequences derived from epidemiologically linked samples and, surprisingly, find relative homogeneity amongst these datasets. We found no evidence of positive selection for amino acid substitution in the HVR. Through an analysis of published sequences, we conclude that the range of HVR diversity observed within virus genotypes can be explained by the accumulation of substitutions and, to a much lesser extent, through deletions or duplications of this region. All published HVR amino acid sequences display a relative overabundance of proline and serine residues that cannot be explained by a local bias towards cytosine in this part of the genome. Although all published HVRs contain one or more SH3-binding PxxP motifs, this motif does not occur more frequently than would be expected from the proportion of proline residues in these sequences. Taken together, these observations are consistent with the hypothesis that the HVR has a structural role that is dependent upon length and amino acid composition, rather than a specific sequence.
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