AT LEAST 12 GENOTYPES OF HEPATITIS-C VIRUS PREDICTED BY SEQUENCE-ANALYSIS OF THE PUTATIVE E1-GENE OF ISOLATES COLLECTED WORLDWIDE
AT LEAST 12 GENOTYPES OF HEPATITIS-C VIRUS PREDICTED BY SEQUENCE-ANALYSIS OF THE PUTATIVE E1-GENE OF ISOLATES COLLECTED WORLDWIDE
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DOI：
10.1073/pnas.90.17.8234
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发表时间：
1993-09-01
影响因子：
11.1
通讯作者：
MILLER, RH
中科院分区：
文献类型：
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作者：
BUKH, J;PURCELL, RH;MILLER, RH
在先前的研究中，我们对44株丙型肝炎病毒（HCV）分离株的5'非编码区（NC）进行了测序，并确定了异质结构域，为以前未认识到的HCV其他遗传群提供了证据。 在这项研究中，我们已经确定了完整的核苷酸序列的推定包膜1（E1）基因在51个HCV分离株来自世界各地，发现他们可以分为至少12个不同的基因型。 其中8个基因型的E1基因序列未见报道。尽管通过先前对5' NC区的分析确定的HCV分离株的遗传相关性预测了在E1基因中观察到的关系，但单独对5' NC序列的分析不能准确预测所有HCV基因型。同一基因型HCV E1基因核苷酸和氨基酸序列同源性分别为88.0-99.1%和89.1- 98.4%，不同基因型HCV E1基因核苷酸和氨基酸序列同源性分别为53.5-78.6%和49.0- 82.8%。后者的差异与比较相关黄病毒以及其他RNA病毒的各种血清型的包膜基因序列时发现的差异相似。我们发现，HCV的一些基因型广泛分布在世界各地，而其他人只在谨慎的地理区域确定。四种基因型仅在Aftica发现，并构成该大陆上大多数HCV分离株。所有51株HCV分离株的E1基因长度均为576个核苷酸，无框内终止密码子。对预测的El蛋白的分析鉴定了可能对维持其生物学功能重要的几个保守结构域：（i）八个不变的半胱氨酸残基，（ii）三个潜在的N-连接的糖基化位点，（iii）九个氨基酸的结构域（GHRMAWDMM），和（iv）在蛋白质的C末端的推定切割位点附近的氨基酸双联体（GV）。 总之，发现至少12种HCV基因型对HCV诊断和疫苗开发具有重要意义。
In a previous study we sequenced the 5' noncoding (NC) region of 44 isolates of hepatitis C virus (HCV) and identified heterogeneous domains that provided evidence for additional genetic groups of HCV not previously recognized. In this study we have determined the complete nucleotide sequence of the putative envelope 1 (E1) gene in 51 HCV isolates from around the world and found that they could be grouped into at least 12 distinct genotypes. The E1 gene sequence of 8 of these genotypes has not been reported previously. Although the genetic relatedness of HCV isolates determined by the previous analysis of the 5' NC region predicted the relationships observed in the E1 gene, analysis of the 5' NC sequence alone did not accurately predict all HCV genotypes. The nucleotide and amino acid sequence identities of the E1 gene among HCV isolates of the same genotype were in the range of 88.0-99.1% and 89.1-98.4%, respectively, whereas those of HCV isolates of different genotypes were in the range of 53.5-78.6% and 49.0-82.8%, respectively. The latter differences are similar to those found when comparing the envelope gene sequences of the various serotypes of the related flaviviruses as well as other RNA viruses. We found that some genotypes of HCV were widely distributed around the world, whereas others were identified only in discreet geographical regions. Four genotypes were identified exclusively in Aftica and comprised the majority of HCV isolates on that continent. The E1 gene was exactly 576 nucleotides in length in all 51 HCV isolates with no in-frame stop codons. Analysis of the predicted El protein identified several conserved domains that may be important for maintaining its biological function: (i) eight invariant cysteine residues, (ii) three potential N-linked glycosylation sites, (iii) a domain of nine amino adds (GHRMAWDMM), and (iv) an amino acid doublet (GV) near the putative cleavage site at the C terminus of the protein. In conclusion, the discovery of at least 12 genotypes of HCV has important implications for HCV diagnosis and vaccine development.