Infection and Pathogenesis of Canine, Equine, and Human Influenza Viruses in Canine Tracheas
Infection and Pathogenesis of Canine, Equine, and Human Influenza Viruses in Canine Tracheas
复制标题
DOI：
10.1128/jvi.00887-14
复制
发表时间：
2014-08-01
影响因子：
5.4
通讯作者：
Murcia, Pablo R.
中科院分区：
文献类型：
--
作者：
Gonzalez, Gaelle;Marshall, John F.;Murcia, Pablo R.
甲型流感病毒(IAV)可以跨越物种障碍，偶尔会引发流行病、家禽流行性疾病、大流行和动物疫病。研究自然寄主目标组织的侵染动态对于理解控制寄主范围、嗜性和毒力的机制至关重要。犬流感病毒(CIV；H3N8)起源于将马流感病毒(EIV)转移到狗体内。因此，比较CIV和EIV分离株为研究流感病毒出现的决定因素提供了机会。在这里，我们描述了犬、马和人类IAV在狗的气管内复制的特征，这是人类严重接触的一个物种。我们定义了CIV感染的表型，其特征是高水平的病毒复制和广泛的组织损伤。将CIV与进化上不同的EIV进行比较，早期EIV分离株感染犬气管的能力减弱，而在CIV出现时传播的EIV表现出类似CIV的感染表型。用不同的人免疫缺陷病毒(HIAV)接种狗的气管，结果表明，它们感染气管上皮的效果因所测试的病毒而异。最后，我们证明了携带CIV和hIAV基因片段的重组病毒是可行的，并且将CIV的血凝素(HA)和神经氨酸酶(NA)添加到2009年人类大流行病毒中导致了一种高水平复制并造成重大损害的病毒。这为进化在病毒出现中的作用以及HA和NA作为致病性决定因素的作用提供了重要的见解。
Influenza A viruses (IAVs) can jump species barriers and occasionally cause epidemics, epizootics, pandemics, and panzootics. Characterizing the infection dynamics at the target tissues of natural hosts is central to understanding the mechanisms that control host range, tropism, and virulence. Canine influenza virus (CIV; H3N8) originated after the transfer of an equine influenza virus (EIV) into dogs. Thus, comparing CIV and EIV isolates provides an opportunity to study the determinants of influenza virus emergence. Here we characterize the replication of canine, equine, and human IAVs in the trachea of the dog, a species to which humans are heavily exposed. We define a phenotype of infection for CIV, which is characterized by high levels of virus replication and extensive tissue damage. CIV was compared to evolutionarily distinct EIVs, and the early EIV isolates showed an impaired ability to infect dog tracheas, while EIVs that circulated near the time of CIV emergence exhibited a CIV-like infection phenotype. Inoculating dog tracheas with various human IAVs (hIAVs) showed that they infected the tracheal epithelium with various efficiencies depending on the virus tested. Finally, we show that reassortant viruses carrying gene segments of CIV and hIAV are viable and that addition of the hemagglutinin (HA) and neuraminidase (NA) of CIV to the 2009 human pandemic virus results in a virus that replicates at high levels and causes significant lesions. This provides important insights into the role of evolution on viral emergence and on the role of HA and NA as determinants of pathogenicity.