Natural selection on the influenza virus genome
Natural selection on the influenza virus genome
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DOI：
10.1093/molbev/msl050
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发表时间：
2006-10-01
影响因子：
10.7
通讯作者：
Suzuki, Yoshiyuki
中科院分区：
文献类型：
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作者：
Suzuki, Yoshiyuki
流感病毒是流感的病原体。尽管疫苗和药物可用于预防和治疗流感病毒感染，但已报道了逃逸突变体的产生。为了开发不易产生逃逸突变体的疫苗和药物，了解病毒的进化机制非常重要。在这里，通过比较每个位点的同义（d（S）[D-S]）和非同义（d（N）[D-N]）取代的数量，推断出对H3 N2人类甲型流感病毒基因组编码的所有蛋白质起作用的自然选择。自然选择也推断出B细胞表位（BCEs），T细胞表位（TCEs），耐药性和鸡蛋中的生长所涉及的功能氨基酸位点的组。PB 1-F2的整个区域被正向选择，并且正向选择似乎也对BCE、TCE和卵中的生长起作用。逃逸突变体的产生频率似乎与疫苗和药物的靶点的d（N）/d（S）（D-N/D-S）值正相关，这表明在强功能约束下的氨基酸位点是合适的靶点。特别地，TCE可以代表候选靶标，因为d（N）/d（S）（D-N/D-S）值很小，并且对于它们中的许多推断出负选择。
Influenza viruses are the etiological agents of influenza. Although vaccines and drugs are available for the prophylaxis and treatment of influenza virus infections, the generation of escape mutants has been reported. To develop vaccines and drugs that are less susceptible to the generation of escape mutants, it is important to understand the evolutionary mechanisms of the viruses. Here natural selection operating on all the proteins encoded by the H3N2 human influenza A virus genome was inferred by comparing the numbers of synonymous (d(S) [D-S]) and nonsynonymous (d(N) [D-N]) substitutions per site. Natural selection was also inferred for the groups of functional amino acid sites involved in B-cell epitopes (BCEs), T-cell epitopes (TCEs), drug resistance, and growth in eggs. The entire region of PB1-F2 was positively selected, and positive selection also appeared to operate on BCEs, TCEs, and growth in eggs. The frequency of escape mutant generation appeared to be positively correlated with the d(N)/d(S) (D-N/D-S) values for the targets of vaccines and drugs, suggesting that the amino acid sites under strong functional constraint are suitable targets. In particular, TCEs may represent candidate targets because the d(N)/d(S) (D-N/D-S) values were small and negative selection was inferred for many of them.