Airborne transmission of influenza A/H5N1 virus between ferrets.
Airborne transmission of influenza A/H5N1 virus between ferrets.
复制标题
DOI：
10.1126/science.1213362
复制
发表时间：
2012-06-22
期刊：
影响因子：
--
通讯作者：
Fouchier RA
中科院分区：
文献类型：
--
作者：
Herfst S;Schrauwen EJ;Linster M;Chutinimitkul S;de Wit E;Munster VJ;Sorrell EM;Bestebroer TM;Burke DF;Smith DJ;Rimmelzwaan GF;Osterhaus AD;Fouchier RA
高致病性禽流感A/H5 N1病毒可导致人类发病和死亡，但迄今为止尚未获得通过气溶胶或呼吸道飞沫在人类之间传播的能力（“空气传播”）。为了解决病毒在自然条件下获得这种能力的问题，我们通过定点突变和随后在雪貂中连续传代对A/H5 N1病毒进行了遗传修饰。转基因的A/H5 N1病毒在雪貂体内传播过程中发生突变，最终可通过空气传播。没有一只受体雪貂在空气中感染变异的A/H5 N1病毒后死亡。宿主受体结合蛋白血凝素中的四个氨基酸取代和聚合酶复合体蛋白碱性聚合酶2中的一个氨基酸取代在空气传播的病毒中始终存在。这些可传播的病毒对抗病毒药物奥司他韦敏感，并与针对H5流感疫苗株的抗血清反应良好。因此，禽流感A/H5 N1病毒可以获得在哺乳动物之间通过空气传播的能力，而无需在中间宿主中重组，因此构成人类大流行性流感的风险。
Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet (“airborne transmission”) between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza.