Fecal Influenza in Mammals: Selection of Novel Variants
Fecal Influenza in Mammals: Selection of Novel Variants
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DOI：
10.1128/jvi.01544-13
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发表时间：
2013-11-01
影响因子：
5.4
通讯作者：
Webstera, Robert G.
中科院分区：
文献类型：
--
作者：
Kocer, Zeynep A.;Obenauer, John;Webstera, Robert G.
在水禽中，甲型流感病毒主要在肠道内复制，不会明显影响宿主的健康，但在哺乳动物中，它们在呼吸道内复制，往往会引起疾病。偶尔，在住院患者的粪便样本和自然或实验感染哺乳动物的直肠拭子中检测到流感病毒。在这项研究中，我们比较了四个野生型禽流感病毒H1N1及其相应的粪便和肺分离株在DBA/2 J和BALB/cJ小鼠的生物学和分子差异。所有粪便和肺分离株的致病性比原来的野生型病毒，接种到小鼠的两个菌株。毒力的增加与基因突变的获得有关。大多数新的基因型出现PB 2（E627 K），HA（F128 V），HA（F454 L），或HA（H300 P）的变化，和双突变经常发生在同一个分离物。然而，在选定的变异体方面也观察到流感病毒株特异性和宿主特异性差异。与野鸭来源的H1N1病毒的适应性相比，水鸟来源的禽H1N1病毒通过粪便途径迅速适应BALB/cJ小鼠的能力似乎是独特的。此外，在感染粪便分离株的小鼠中观察到粪便脱落的双峰分布，而在感染肺分离株或野生型病毒后观察到正态分布。粪便分离物含有HA突变，其增加了HA蛋白的活化pH。我们的结论是，在哺乳动物粪便分离株中出现的流感病毒变异可能会影响病毒的传播，适应哺乳动物，以及病毒的生态或进化。
In aquatic birds, influenza A viruses mainly replicate in the intestinal tract without significantly affecting the health of the host, but in mammals, they replicate in the respiratory tract and often cause disease. Occasionally, influenza viruses have been detected in stool samples of hospitalized patients and in rectal swabs of naturally or experimentally infected mammals. In this study, we compared the biological and molecular differences among four wild-type avian H1N1 influenza viruses and their corresponding fecal and lung isolates in DBA/2J and BALB/cJ mice. All fecal and lung isolates were more pathogenic than the original wild-type viruses, when inoculated into mice of both strains. The increased virulence was associated with the acquisition of genetic mutations. Most of the novel genotypes emerged as PB2(E627K), HA(F128V), HA(F454L), or HA(H300P) variations, and double mutations frequently occurred in the same isolate. However, influenza virus strain-and host-specific differences were also observed in terms of selected variants. The avian H1N1 virus of shorebird origin appeared to be unique in its ability to rapidly adapt to BALB/cJ mice via the fecal route, compared to the adaptability of the H1N1 virus of mallard origin. Furthermore, a bimodal distribution in fecal shedding was observed in mice infected with the fecal isolates, while a normal distribution was observed after infection with the lung isolates or wild-type virus. Fecal isolates contained HA mutations that increased the activation pH of the HA protein. We conclude that influenza virus variants that emerge in fecal isolates in mammals might influence viral transmission, adaptation to mammals, and viral ecology or evolution.