Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine.
Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine.
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DOI：
10.1016/j.chom.2017.08.021
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发表时间：
2017-10-11
影响因子：
30.3
通讯作者：
Virgin HW
中科院分区：
文献类型：
--
作者：
Lee S;Wilen CB;Orvedahl A;McCune BT;Kim KW;Orchard RC;Peterson ST;Nice TJ;Baldridge MT;Virgin HW
持续病毒感染期间的细胞趋向性通常是由病毒表面蛋白与宿主受体复合物的相互作用所赋予的。诺如病毒是全球胃肠炎的主要病因，在感染期间可持续传播，但其体内细胞的趋向性和趋向性决定因素仍未确定。使用小鼠诺如病毒（MNoV），我们确定了少量肠上皮细胞（IECs）作为粪便脱落和持久性的储存库。病毒非结构蛋白NS1，而不是病毒表面蛋白，决定了IEC的趋向性。从持续性MNoV菌株中表达NS1足以使急性MNoV菌株靶向IECs并持续存在。此外，干扰素-λ (IFN-λ)是阻断IECs中MNoV感染的关键宿主决定因子。在Ifnlr1−/−小鼠中，急性MNoV无法脱落和持续存在，这表明NS1逃避了IFN-λ介导的抗病毒免疫。因此，NS1和IFN-λ相互作用控制了MNoV的IEC趋向性和持久性。胃肠病原体诺如病毒的体内嗜性尚不清楚。Lee等人发现，少量肠上皮细胞是持久性小鼠诺如病毒的储存库。这种趋向性是由病毒蛋白NS1和宿主IFN-lambda调节的，这一发现为诺如病毒的发病机制提供了重要的见解。
Cellular tropism during persistent viral infection is commonly conferred by the interaction of a viral surface protein with a host receptor complex. Norovirus, the leading global cause of gastroenteritis, can be persistently shed during infection, but its in vivo cellular tropism and tropism determinants remain unidentified. Using murine norovirus (MNoV), we determine that a small number of intestinal epithelial cells (IECs) serve as the reservoir for fecal shedding and persistence. The viral non-structural protein NS1, rather than a viral surface protein, determines IEC tropism. Expression of NS1 from a persistent MNoV strain is sufficient for an acute MNoV strain to target IECs and persist. Additionally, interferon-lambda (IFN-λ) is a key host determinant blocking MNoV infection in IECs. The inability of acute MNoV to shed and persist is rescued in Ifnlr1−/− mice, suggesting that NS1 evades IFN-λ-mediated antiviral immunity. Thus, NS1 and IFN-λ interactions govern IEC tropism and persistence of MNoV. The in vivo tropism of norovirus, a gastrointestinal pathogen, is unknown. Lee et al. discover that a small number of intestinal epithelial cells are a reservoir for persistent murine norovirus. This tropism is regulated by viral protein NS1 and host IFN-lambda, findings that provide critical insight into norovirus pathogenesis.
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