Infection and Replication of Influenza Virus at the Ocular Surface
Infection and Replication of Influenza Virus at the Ocular Surface
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DOI：
10.1128/jvi.02192-17
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发表时间：
2018-04-01
影响因子：
5.4
通讯作者：
Belser, Jessica A.
中科院分区：
文献类型：
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作者：
Creager, Hannah M.;Kumar, Amrita;Belser, Jessica A.
虽然流感病毒通常会引起呼吸道疾病，但从结膜炎患者的眼睛中已分离出一些病毒，特别是带有H7血凝素的病毒。先前的研究表明，来自眼部和呼吸道感染的多种亚型分离株能够在人离体眼部组织和角膜或结膜细胞单层中复制，这使得眼向性的决定因素尚不清楚。在这里，我们评估了几个变量对体外培养的眼细胞趋向性的影响，并检查了泪膜对病毒感染性的潜在影响。所有测试的病毒都能在气溶胶接种的原代人角膜上皮细胞单层中复制。接种后培养细胞的温度对感染性影响最小。相反，复制效率在33℃时比在37℃时降低，而且结膜炎分离株的这种影响略大于呼吸道分离株。除季节性H3N2病毒外，在多层角膜组织结构中研究的病毒亚群在气溶胶或液体接种后也能有效地复制。人泪液能显著抑制眼部和非眼部分离株的血凝作用，但对病毒感染性的影响差异较大，泪液对非眼部分离株的感染性的降低作用大于眼部分离株。这些数据表明，大多数流感病毒在到达眼细胞表面时可能能够建立感染，但这更可能发生在亲眼病毒身上，因为它们在穿过泪膜时能够更好地保持其传染性。人畜共患流感病毒对人类的潜在传播是对公共卫生的重大威胁。不幸的是，尽管细胞和组织趋向性对发病机制的重要性，但流感病毒趋向性的决定因素尚未完全阐明。在这里，我们试图确定限制大多数流感病毒引起眼部感染的能力的因素。虽然禽流感病毒引起的人类眼部症状往往相对较轻，但由于眼表可能成为病毒进入的门户，进而引起呼吸道感染，因此这些感染令人担忧。此外，更好地了解影响非典型位点感染和复制的因素可能会指向呼吸道嗜性的新决定因素。
Although influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human ex vivo ocular tissues and corneal or conjunctival cell monolayers, leaving the determinants of ocular tropism unclear. Here, we evaluated the effect of several variables on tropism for ocular cells cultured in vitro and examined the potential effect of the tear film on viral infectivity. All viruses tested were able to replicate in primary human corneal epithelial cell monolayers subjected to aerosol inoculation. The temperature at which cells were cultured postinoculation minimally affected infectivity. Replication efficiency, in contrast, was reduced at 33 degrees C relative to that at 37 degrees C, and this effect was slightly greater for the conjunctivitis isolates than for the respiratory ones. With the exception of a seasonal H3N2 virus, the subset of viruses studied in multilayer corneal tissue constructs also replicated productively after either aerosol or liquid inoculation. Human tears significantly inhibited the hemagglutination of both ocular and nonocular isolates, but the effect on viral infectivity was more variable, with tears reducing the infectivity of nonocular isolates more than ocular isolates. These data suggest that most influenza viruses may be capable of establishing infection if they reach the surface of ocular cells but that this is more likely for ocular- tropic viruses, as they are better able to maintain their infectivity during passage through the tear film.IMPORTANCE The potential spread of zoonotic influenza viruses to humans represents an important threat to public health. Unfortunately, despite the importance of cellular and tissue tropism to pathogenesis, determinants of influenza virus tropism have yet to be fully elucidated. Here, we sought to identify factors that limit the ability of most influenza viruses to cause ocular infection. Although ocular symptoms in humans caused by avian influenza viruses tend to be relatively mild, these infections are concerning due to the potential of the ocular surface to serve as a portal of entry for viruses that go on to establish respiratory infections. Furthermore, a better understanding of the factors that influence infection and replication in this noncanonical site may point toward novel determinants of tropism in the respiratory tract.