Zhang W, Cox A G, Taylor E W
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, USA.
Med Klin (Munich). 1999 Oct 15;94 Suppl 3:2-6. doi: 10.1007/BF03042181.
Using structural bioinformatics methods, the aim is to assess the hypothesis that hepatitis C virus (HCV) encodes a glutathione peroxidase (GPx) gene in an overlapping reading frame, linking HCV expression and pathogenesis to the Se status and dietary oxidant/Antioxidant balance of the host.
The putative HCV GPx gene was identified by searching viral sequence databases, using conserved GPx active site sequences as probes, giving particular weight to the UGA (selenocysteine) codon. Multiple sequence alignments were generated and analyzed to validate the sequence similarity, and to establish the degree of conservation of the identified genomic features in HCV. Molecular modeling was used to assess the structural feasibility of the proposed homology.
The GPx homology region overlaps the NS4 gene, and is well conserved in HCV. The sequence similarity of the conserved active site regions to a set of known GPx is high (4 to 6 SD greater than expected for similar random sequences). The computed strain energy of a molecular model of the HCV GPx is energetically favorable, comparable to the bovine GPx structure.
By linking HCV replication and pathogenesis to the Se status and dietary oxidant/antioxidant balance of the host, the existence of a viral GPx gene could help to explain why HCV disease progression is accelerated by oxidant stresses such as alcoholism and iron overload.
运用结构生物信息学方法，旨在评估丙型肝炎病毒（HCV）在重叠阅读框中编码谷胱甘肽过氧化物酶（GPx）基因这一假说，该假说将HCV的表达和发病机制与宿主的硒状态及饮食中的氧化剂/抗氧化剂平衡联系起来。
通过搜索病毒序列数据库，以保守的GPx活性位点序列为探针，特别关注UGA（硒代半胱氨酸）密码子，来鉴定假定的HCV GPx基因。生成并分析多序列比对，以验证序列相似性，并确定HCV中已鉴定基因组特征的保守程度。运用分子建模来评估所提出同源性的结构可行性。
GPx同源区域与NS4基因重叠，且在HCV中高度保守。保守活性位点区域与一组已知GPx的序列相似性很高（比相似随机序列预期的高4至6个标准差）。HCV GPx分子模型的计算应变能在能量上是有利的，与牛GPx结构相当。
通过将HCV复制和发病机制与宿主的硒状态及饮食中的氧化剂/抗氧化剂平衡联系起来，病毒GPx基因的存在有助于解释为何酗酒和铁过载等氧化应激会加速HCV疾病进展。
