PDF(Pubmed)
Abstract：
Influenza C virus (ICV) is increasingly associated with community-acquired pneumonia (CAP) in children and its disease severity is worse than the influenza B virus, but similar to influenza A virus associated CAP. Despite the ubiquitous infection landscape of ICV in humans, little is known about its replication and pathobiology in animals. The goal of this study was to understand the replication kinetics, tissue tropism, and pathogenesis of human ICV (huICV) in comparison to the swine influenza D virus (swIDV) in guinea pigs. Intranasal inoculation of both viruses did not cause clinical signs, however, the infected animals shed virus in nasal washes. The huICV replicated in the nasal turbinates, soft palate, and trachea but not in the lungs while swIDV replicated in all four tissues. A comparative analysis of tropism and pathogenesis of these two related seven-segmented influenza viruses revealed that swIDV-infected animals exhibited broad tissue tropism with an increased rate of shedding on 3, 5, and 7 dpi and high viral loads in the lungs compared to huICV. Seroconversion occurred late in the huICV group at 14 dpi, while swIDV-infected animals seroconverted at 7 dpi. Guinea pigs infected with huICV exhibited mild to moderate inflammatory changes in the epithelium of the soft palate and trachea, along with mucosal damage and multifocal alveolitis in the lungs. In summary, the replication kinetics and pathobiological characteristics of ICV in guinea pigs agree with the clinical manifestation of ICV infection in humans, and hence guinea pigs could be used to study these distantly related influenza viruses. IMPORTANCE Similar to influenza A and B, ICV infections are seen associated with bacterial and viral co-infections which complicates the assessment of its real clinical significance. Further, the antivirals against influenza A and B viruses are ineffective against ICV which mandates the need to study the pathobiological aspects of this virus. Here we demonstrated that the respiratory tract of guinea pigs possesses specific viral receptors for ICV. We also compared the replication kinetics and pathogenesis of huICV and swIDV, as these viruses share 50% sequence identity. The tissue tropism and pathology associated with huICV in guinea pigs are analogous to the mild respiratory disease caused by ICV in humans, thereby demonstrating the suitability of guinea pigs to study ICV. Our comparative analysis revealed that huICV and swIDV replicated differentially in the guinea pigs suggesting that the type-specific genetic differences can result in the disparity of the viral shedding and tissue tropism.
摘要：
C型流感病毒（ICV）与儿童社区获得性肺炎（CAP）的关系日益密切，其病情严重程度比B型流感病毒更为严重。但与甲型流感病毒相关的CAP相似。尽管ICV在人类中无处不在，对其在动物中的复制和病理生物学知之甚少。这项研究的目的是了解复制动力学，组织嗜性,与豚鼠中的猪D型流感病毒（swIDV）相比，人ICV（huICV）的发病机理。鼻内接种两种病毒均未引起临床症状，然而,受感染的动物在鼻洗液中释放病毒。在鼻甲复制的huICV，软腭,和气管，但不在肺中，而swIDV在所有四个组织中复制。对这两种相关的七段流感病毒的嗜性和发病机理的比较分析显示，与huICV相比，swIDV感染的动物表现出广泛的组织嗜性，在3、5和7dpi的脱落率和肺中的高病毒载量增加。huICV组在14dpi时出现血清转换，而感染swIDV的动物在7dpi时血清转化。感染huICV的豚鼠在软腭和气管的上皮中表现出轻度至中度的炎症变化，伴随着粘膜损伤和肺部多灶性肺泡炎。总之,豚鼠ICV的复制动力学和病理生物学特征与人类ICV感染的临床表现一致，因此，豚鼠可用于研究这些远缘相关的流感病毒。重要性类似于甲型和乙型流感，观察到ICV感染与细菌和病毒共感染相关,这使得对其实际临床意义的评估复杂化。Further,针对甲型和乙型流感病毒的抗病毒药物对ICV无效，这要求需要研究该病毒的病理生物学方面。在这里，我们证明了豚鼠的呼吸道具有ICV的特异性病毒受体。我们还比较了huICV和swIDV的复制动力学和发病机理，因为这些病毒共有50%的序列同一性。豚鼠与huICV相关的组织嗜性和病理学类似于人类由ICV引起的轻度呼吸道疾病，从而证明了豚鼠研究ICV的适用性。我们的比较分析表明，huICV和swIDV在豚鼠中的复制差异表明，特定类型的遗传差异可能导致病毒脱落和组织嗜性的差异。
