Hepatitis C virus F protein sequence reveals a lack of functional constraints and a variable pattern of amino acid substitution
Hepatitis C virus F protein sequence reveals a lack of functional constraints and a variable pattern of amino acid substitution
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DOI：
10.1099/vir.0.80510-0
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发表时间：
2005-01-01
影响因子：
3.8
通讯作者：
Chunga, A
中科院分区：
文献类型：
--
作者：
Cristina, J;Lopez, F;Chunga, A
丙型肝炎病毒（HCV）是一种重要的人类病原体，影响着全世界1.7亿人。HCV基因组是一个长度约9.6 kb的RNA分子，编码一种多蛋白，该多蛋白被蛋白水解裂解以产生至少10种成熟的病毒蛋白。最近，一种新的HCV蛋白被描述为IF，它是由核糖体移码合成的。目前对该蛋白的生物学特性知之甚少，但IF蛋白参与HCV形态或复制的可能性已被提出。在这项工作中，研究了F蛋白中存在的功能限制。研究发现，沿F蛋白的氨基酸替换率明显高于同义替换率，并且涉及代表独立系统发育谱系的基因的比较产生了非常不同的分化/保守模式。我们还研究了F蛋白中终止密码子在所有HCV基因型中的分布；基因型2和3比基因型1有更多的终止密码子。这项工作的结果强烈表明，F蛋白的分化模式不受功能限制的影响。
Hepatitis C virus (HCV) is an important human pathogen that affects 170 million people worldwide. The HCV genome is an RNA molecule that is approximately 9.6 kb in length and encodes a polyprotein that is cleaved proteolytically to generate at least 10 mature viral proteins. Recently, a new HCV protein named IF has been described, which is synthesized as a result of a ribosomal frameshift. Little is known about the biological properties of this protein, but the possibility that the IF protein may participate in HCV morphology or replication has been raised. In this work, the presence of functional constraints in the F protein was investigated. It was found that the rate of amino acid substitutions along the F protein was significantly higher than the rate of synonymous substitutions, and comparisons involving genes that represented independent phylogenetic lineages yielded very different divergence/conservation patterns. The distribution of stop codons in the F protein across all HCV genotypes was also investigated; genotypes 2 and 3 were found to have more stop codons than genotype 1. The results of this work suggest strongly that the pattern of divergence in the F protein is not affected by functional constraints.