Seligman Stephen J
Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, USA.
Virol J. 2008 Feb 14;5:27. doi: 10.1186/1743-422X-5-27.
Flaviviruses include the mosquito-borne dengue, Japanese encephalitis, yellow fever and West Nile and the tick-borne encephalitis viruses. They are responsible for considerable world-wide morbidity and mortality. Viral entry is mediated by a conserved fusion peptide containing 16 amino acids located in domain II of the envelope protein E. Highly orchestrated conformational changes initiated by exposure to acidic pH accompany the fusion process and are important factors limiting amino acid changes in the fusion peptide that still permit fusion with host cell membranes in both arthropod and vertebrate hosts. The cell-fusing related agents, growing only in mosquitoes or insect cell lines, possess a different homologous peptide.
Analysis of 46 named flaviviruses deposited in the Entrez Nucleotides database extended the constancy in the canonical fusion peptide sequences of mosquito-borne, tick-borne and viruses with no known vector to include more recently-sequenced viruses. The mosquito-borne signature amino acid, G104, was also found in flaviviruses with no known vector and with the cell-fusion related viruses. Despite the constancy in the canonical sequences in pathogenic flaviviruses, mutations were surprisingly frequent with a 27% prevalence of nonsynonymous mutations in yellow fever virus fusion peptide sequences, and 0 to 7.4% prevalence in the others. Six of seven yellow fever patients whose virus had fusion peptide mutations died. In the cell-fusing related agents, not enough sequences have been deposited to estimate reliably the prevalence of fusion peptide mutations. However, the canonical sequences homologous to the fusion peptide and the pattern of disulfide linkages in protein E differed significantly from the other flaviviruses.
The constancy of the canonical fusion peptide sequences in the arthropod-borne flaviviruses contrasts with the high prevalence of mutations in most individual viruses. The discrepancy may be the result of a survival advantage accompanying sequence diversity (quasispecies) involving the fusion peptide. Limited clinical data with yellow fever virus suggest that the presence of fusion peptide mutants is not associated with a decreased case fatality rate. The cell-fusing related agents may have substantial differences from other flaviviruses in their mechanism of viral entry into the host cell.
黄病毒包括蚊媒传播的登革热病毒、日本脑炎病毒、黄热病毒和西尼罗河病毒以及蜱传脑炎病毒。它们在全球范围内导致了相当高的发病率和死亡率。病毒进入是由包膜蛋白E结构域II中一个含16个氨基酸的保守融合肽介导的。暴露于酸性pH引发的高度协调的构象变化伴随着融合过程，并且是限制融合肽中氨基酸变化的重要因素，这些变化仍允许在节肢动物和脊椎动物宿主中与宿主细胞膜融合。细胞融合相关因子仅在蚊子或昆虫细胞系中生长，具有不同的同源肽。
对Entrez核苷酸数据库中46种命名的黄病毒进行分析，扩展了蚊媒传播、蜱传和无已知传播媒介病毒的典型融合肽序列的一致性，以纳入最近测序的病毒。在无已知传播媒介的黄病毒和细胞融合相关病毒中也发现了蚊媒传播的特征性氨基酸G104。尽管致病性黄病毒的典型序列具有一致性，但突变却出奇地频繁，黄热病毒融合肽序列中非同义突变的发生率为27%，其他病毒的发生率为0至7.4%。病毒具有融合肽突变的7名黄热患者中有6人死亡。在细胞融合相关因子中，已存入的序列不足，无法可靠估计融合肽突变的发生率。然而，与融合肽同源的典型序列以及蛋白E中的二硫键连接模式与其他黄病毒有显著差异。
节肢动物传播的黄病毒中典型融合肽序列的一致性与大多数单个病毒中高发生率的突变形成对比。这种差异可能是融合肽序列多样性（准种）带来的生存优势的结果。黄热病毒的有限临床数据表明，融合肽突变体的存在与病死率降低无关。细胞融合相关因子在病毒进入宿主细胞的机制上可能与其他黄病毒有很大差异。
