Identification of chicken CAR homology as a cellular receptor for the emerging highly pathogenic fowl adenovirus 4 via unique binding mechanism
Identification of chicken CAR homology as a cellular receptor for the emerging highly pathogenic fowl adenovirus 4 via unique binding mechanism
复制标题
通过独特的结合机制鉴定鸡 CAR 同源性作为新兴高致病性禽腺病毒 4 的细胞受体
DOI：
10.1080/22221751.2020.1736954
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发表时间：
2020-01-01
影响因子：
13.2
通讯作者：
Wang, Xiaomei
中科院分区：
文献类型：
--
作者：
Pan, Qing;Wang, Jing;Wang, Xiaomei
自2015年以来，由新基因型禽腺病毒血清型4（FAdV-4）引起的重症肝炎-心包积液综合征在中国的患病率有所增加，并导致了相当大的经济损失。FAdV-4的复制周期，特别是新出现的高致病性新基因型FAdV-4，在很大程度上仍然是未知的。腺病毒纤维与细胞受体相互作用作为腺病毒（AdV）感染的初始步骤。在我们以前的研究中，完整的基因组序列显示FAdV-4的纤维模式与所有其他AdV不同。在这里，进行蛋白质阻断和抗体中和测定以确认新型FAdV-4短纤维对于结合易感的来航雄性肝细胞（LMH）细胞是关键的。随后，使用纤维1作为诱饵，通过质谱法研究LMH细胞上的受体。在竞争试验中，鸡科萨基和腺病毒受体（CAR）蛋白被证实为FAdV-4的新受体。我们进一步鉴定了CAR的D2结构域（D2-CAR）作为负责与新型FAdV-4的短纤维结合的活性结构域。总之，这些发现首次证明鸡CAR同源物是新型FAdV-4的细胞受体，其通过D2结构域与病毒短纤维相互作用促进病毒进入。总的来说，这些发现提供了一个深入了解的机制，新兴的新基因型FAdV-4的入侵和发病机制。
Since 2015, the prevalence of severe hepatitis-hydropericardium syndrome, which is caused by the novel genotype fowl adenovirus serotype 4 (FAdV-4), has increased in China and led to considerable economic losses. The replication cycle of FAdV-4, especially the emerging highly pathogenic novel genotype FAdV-4, remains largely unknown. The adenovirus fibre interacts with the cellular receptor as the initial step in adenovirus (AdV) infection. In our previous studies, the complete genome sequence showed that the fibre patterns of FAdV-4 were distinct from all other AdVs. Here, protein-blockage and antibody-neutralization assays were performed to confirm that the novel FAdV-4 short fibre was critical for binding to susceptible leghorn male hepatocellular (LMH) cells. Subsequently, fibre 1 was used as bait to investigate the receptor on LMH cells via mass spectrometry. The chicken coxsackie and adenovirus receptor (CAR) protein was confirmed as the novel FAdV-4 receptor in competition assays. We further identified the D2 domain of CAR (D2-CAR) as the active domain responsible for binding to the short fibre of the novel FAdV-4. Taken together, these findings demonstrate for the first time that the chicken CAR homolog is a cellular receptor for the novel FAdV-4, which facilitates viral entry by interacting with the viral short fibre through the D2 domain. Collectively, these findings provide an in-depth understanding of the mechanisms of the emerging novel genotype FAdV-4 invasion and pathogenesis.