Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
J Virol. 2014 Mar;88(6):3127-34. doi: 10.1128/JVI.03155-13. Epub 2013 Dec 26.
Novel avian-origin influenza A(H7N9) viruses were first reported to infect humans in March 2013. To date, 143 human cases, including 45 deaths, have been recorded. By using sequence comparisons and phylogenetic and ancestral inference analyses, we identified several distinct amino acids in the A(H7N9) polymerase PA protein, some of which may be mammalian adapting. Mutant viruses possessing some of these amino acid changes, singly or in combination, were assessed for their polymerase activities and growth kinetics in mammalian and avian cells and for their virulence in mice. We identified several mutants that were slightly more virulent in mice than the wild-type A(H7N9) virus, A/Anhui/1/2013. These mutants also exhibited increased polymerase activity in human cells but not in avian cells. Our findings indicate that the PA protein of A(H7N9) viruses has several amino acid substitutions that are attenuating in mammals.
Novel avian-origin influenza A(H7N9) viruses emerged in the spring of 2013. By using computational analyses of A(H7N9) viral sequences, we identified several amino acid changes in the polymerase PA protein, which we then assessed for their effects on viral replication in cultured cells and mice. We found that the PA proteins of A(H7N9) viruses possess several amino acid substitutions that cause attenuation in mammals.
新型甲型 H7N9 禽流感病毒于 2013 年 3 月首次报告感染人类。迄今为止，已记录到 143 例人类病例，包括 45 例死亡。通过序列比较、系统发育和祖先推断分析，我们在 A(H7N9)聚合酶 PA 蛋白中鉴定出几个不同的氨基酸，其中一些可能是哺乳动物适应的。我们评估了具有这些氨基酸变化中的一些或组合的突变病毒在哺乳动物和禽类细胞中的聚合酶活性和生长动力学，以及在小鼠中的毒力。我们鉴定了一些比野生型 A(H7N9)病毒，A/Anhui/1/2013，在小鼠中略具更高毒力的突变体。这些突变体在人细胞中的聚合酶活性也增加，但在禽类细胞中没有。我们的研究结果表明，A(H7N9)病毒的 PA 蛋白有几个氨基酸取代，在哺乳动物中是减毒的。
新型甲型 H7N9 禽流感病毒于 2013 年春季出现。通过对 A(H7N9)病毒序列的计算分析，我们鉴定了聚合酶 PA 蛋白中的几个氨基酸变化，然后评估了它们对细胞培养和小鼠中病毒复制的影响。我们发现，A(H7N9)病毒的 PA 蛋白具有几个导致在哺乳动物中减毒的氨基酸取代。
