High prevalence of amantadine resistance among circulating European porcine influenza A viruses
High prevalence of amantadine resistance among circulating European porcine influenza A viruses
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DOI：
10.1099/vir.2008.007260-0
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发表时间：
2009-04-01
影响因子：
3.8
通讯作者：
Zell, Roland
中科院分区：
文献类型：
--
作者：
Krumbholz, Andi;Schmidtke, Michaela;Zell, Roland
对欧洲猪甲型流感病毒M2序列的遗传分析显示，由于在H1N1、H3N2和H1N2三种流行亚型中，丝氨酸31被天冬酰胺取代，金刚烷胺耐药的流行率很高。所有耐药菌株的M片段都属于单一遗传谱系。第一个金刚烷胺耐药猪毒株是在1989年分离出来的，最后一个金刚烷胺敏感毒株是在1987年分离出来的，这表明在突变出现后不久，金刚烷胺敏感病毒就被耐药毒株取代了。基于密码子的自然选择分析表明，产生金刚烷胺抗性的密码子30、31和34存在负选择。猪株和人株密码子2、11 ~ 28和54的替代率模式存在差异，说明选择模式不同。通过交换M片段转移金刚烷胺抗性以及重组A/WSN/33病毒与禽样M片段的生存能力引起了人们对自然人类重组病毒出现的担忧。
Genetic analysis of the M2 sequence of European porcine influenza A viruses reveals a high prevalence of amantadine resistance due to the substitution of serine 31 by asparagine in all three circulating subtypes, H1N1, H3N2 and H1N2. The M segment of all resistant strains belongs to a single genetic lineage. Whereas the first amantadine-resistant porcine strain was isolated in 1989, isolation of the last amantadine-susceptible strain dates to 1987, suggesting a displacement of amantadine-susceptible viruses by resistant strains soon after emergence of the mutation. Analysis of natural selection by codon-based tests indicates negative selection of codons 30, 31 and 34 which confer amantadine resistance. The codons 2, 11-28 and 54 of porcine and human strains exhibit differences in the patterns of substitution rates, suggesting different selection modes. Transfer of amantadine resistance by exchange of the M segment and viability of recombinant A/WSN/33 viruses with avian-like M segments raises concerns about the emergence of natural human reassortants.