Ocular Infection of Mice with Influenza A (H7) Viruses: a Site of Primary Replication and Spread to the Respiratory Tract
Ocular Infection of Mice with Influenza A (H7) Viruses: a Site of Primary Replication and Spread to the Respiratory Tract
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DOI：
10.1128/jvi.00535-09
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发表时间：
2009-07-15
影响因子：
5.4
通讯作者：
Tumpey, Terrence M.
中科院分区：
文献类型：
--
作者：
Belser, Jessica A.;Wadford, Debra A.;Tumpey, Terrence M.
禽H7流感病毒是全球家禽暴发的原因，近年来已导致许多人类感染病例。与禽H7亚型病毒感染相关的结膜炎的高发病率可能代表了禽流感病毒的入口，并强调了更好地了解在人类中观察到的明显的眼部嗜性的必要性。为了研究这一点，小鼠通过眼部途径接种多种亚型和毒力程度的病毒。我们发现，与人类（H3 N2和H1 N1）病毒相反，2003年从荷兰分离的H7 N7病毒和2004年从加拿大不列颠哥伦比亚省分离的H7 N3病毒，这两种亚型对家禽具有高度毒性，在小鼠眼中复制到显著滴度。值得注意的是，H7N7病毒以及一些禽类H5N1病毒在眼部接种后全身性传播，包括传播到大脑，导致小鼠发病和死亡。这与高致病性H7和H5亚型在鼠角膜上皮片（离体）和原代人角膜上皮细胞（体外）中的有效复制相关。流感病毒被标记以识别病毒在小鼠角膜中的附着位点。虽然我们发现大量的H7病毒附着在角膜上皮组织上，但这并不能解释病毒复制的差异，因为多种亚型能够附着在这些细胞上。这些发现表明，H7和H5亚型的禽流感病毒能够利用眼睛作为进入的门户。
Avian H7 influenza viruses have been responsible for poultry outbreaks worldwide and have resulted in numerous cases of human infection in recent years. The high rate of conjunctivitis associated with avian H7 subtype virus infections may represent a portal of entry for avian influenza viruses and highlights the need to better understand the apparent ocular tropism observed in humans. To study this, mice were inoculated by the ocular route with viruses of multiple subtypes and degrees of virulence. We found that in contrast to human (H3N2 and H1N1) viruses, H7N7 viruses isolated from The Netherlands in 2003 and H7N3 viruses isolated from British Columbia, Canada, in 2004, two subtypes that were highly virulent for poultry, replicated to a significant titer in the mouse eye. Remarkably, an H7N7 virus, as well as some avian H5N1 viruses, spread systemically following ocular inoculation, including to the brain, resulting in morbidity and mortality of mice. This correlated with efficient replication of highly pathogenic H7 and H5 subtypes in murine corneal epithelial sheets (ex vivo) and primary human corneal epithelial cells (in vitro). Influenza viruses were labeled to identify the virus attachment site in the mouse cornea. Although we found abundant H7 virus attachment to corneal epithelial tissue, this did not account for the differences in virus replication as multiple subtypes were able to attach to these cells. These findings demonstrate that avian influenza viruses within H7 and H5 subtypes are capable of using the eye as a portal of entry.