The major targets of acute norovirus infection are immune cells in the gut-associated lymphoid tissue.
The major targets of acute norovirus infection are immune cells in the gut-associated lymphoid tissue.
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DOI：
10.1038/s41564-017-0057-7
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发表时间：
2017-12
影响因子：
28.3
通讯作者：
Karst SM
中科院分区：
文献类型：
--
作者：
Grau KR;Roth AN;Zhu S;Hernandez A;Colliou N;DiVita BB;Philip DT;Riffe C;Giasson B;Wallet SM;Mohamadzadeh M;Karst SM
诺如病毒是全球食源性胃肠炎爆发和儿童腹泻的主要原因，估计每年造成200，000名儿童死亡。因此，减少诺如病毒相关疾病是一个关键的优先事项。由于对诺如病毒基本致病机理和细胞嗜性的了解有限，疫苗和治疗剂的开发受到阻碍。虽然巨噬细胞、树突状细胞、B细胞和干细胞来源的类肠细胞都可以支持某些诺如病毒在体外的感染，但是定义体内诺如病毒细胞嗜性的努力产生了相互矛盾的结果。一些研究检测到感染的肠道免疫细胞，-，其他研究检测到上皮细胞，还有一些检测到免疫和上皮细胞，-。这些研究的主要局限性在于，它们是在免疫功能低下或无菌宿主、感染时间未知的慢性感染宿主或遵循非生物学相关接种途径的组织切片上进行的。在这里，我们报告说，小鼠诺如病毒口服接种到免疫活性小鼠的主要细胞目标是巨噬细胞，树突状细胞，B细胞和T细胞在肠道相关淋巴组织。重要的是，我们还证明了诺如病毒可以在体外感染T细胞，这是一种以前未被识别的靶标。这些研究结果代表了迄今为止对口服接种的免疫活性宿主在急性感染高峰期的体内诺如病毒细胞嗜性的最广泛的分析，因此它们显着推进了我们对诺如病毒发病机制的基本理解。
Noroviruses are the leading cause of food-borne gastroenteritis outbreaks and childhood diarrhoea globally, estimated to be responsible for 200,000 deaths in children each year, , –. Thus, reducing norovirus-associated disease is a critical priority. Development of vaccines and therapeutics has been hindered by the limited understanding of basic norovirus pathogenesis and cell tropism. While macrophages, dendritic cells, B cells and stem-cell-derived enteroids can all support infection of certain noroviruses in vitro, –, efforts to define in vivo norovirus cell tropism have generated conflicting results. Some studies detected infected intestinal immune cells, , , –, other studies detected epithelial cells, and still others detected immune and epithelial cells, –. Major limitations of these studies are that they were performed on tissue sections from immunocompromised or germ-free hosts, chronically infected hosts where the timing of infection was unknown, or following non-biologically relevant inoculation routes. Here, we report that the dominant cellular targets of a murine norovirus inoculated orally into immunocompetent mice are macrophages, dendritic cells, B cells and T cells in the gut-associated lymphoid tissue. Importantly, we also demonstrate that a norovirus can infect T cells, a previously unrecognized target, in vitro. These findings represent the most extensive analyses to date of in vivo norovirus cell tropism in orally inoculated, immunocompetent hosts at the peak of acute infection and thus they significantly advance our basic understanding of norovirus pathogenesis.
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DOI：
10.1126/science.aaf1220
发表时间：
2016-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Orchard RC;Wilen CB;Doench JG;Baldridge MT;McCune BT;Lee YC;Lee S;Pruett-Miller SM;Nelson CA;Fremont DH;Virgin HW
通讯作者：
Virgin HW
影响因子：
5.4
作者：
Otto, Peter H.;Clarke, Ian N.;Liebler-Tenorio, Elisabeth M.
通讯作者：
Liebler-Tenorio, Elisabeth M.
影响因子：
4.2
作者：
Teunis, P. F. M.;Sukhrie, F. H. A.;Koopmans, M. P. G.
通讯作者：
Koopmans, M. P. G.
影响因子：
5.4
作者：
Gonzalez-Hernandez, Mariam B.;Liu, Thomas;Wobus, Christiane E.
通讯作者：
Wobus, Christiane E.
影响因子：
11.8
作者：
Patel, Manish M.;Widdowson, Marc-Alain;Glass, Roger I.;Akazawa, Kenichiro;Vinje, Jan;Parashar, Umesh D.
通讯作者：
Parashar, Umesh D.