Coupled CRC 2D and ALI 3D Cultures Express Receptors of Emerging Viruses and Are More Suitable for the Study of Viral Infections Compared to Conventional Cell Lines
Coupled CRC 2D and ALI 3D Cultures Express Receptors of Emerging Viruses and Are More Suitable for the Study of Viral Infections Compared to Conventional Cell Lines
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CRC 2D 和 ALI 3D 联合培养物表达新兴病毒的受体，与传统细胞系相比更适合病毒感染的研究
DOI：
10.1155/2020/2421689
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发表时间：
2020-07
影响因子：
4.3
通讯作者：
Hui Li
中科院分区：
文献类型：
--
作者：
Siyu Xia;Jun Liu;Yan Yang;Ming Wu;Hui Li
新出现和再次出现的病毒(SARS冠状病毒、H1N1流感等)的感染在很大程度上和全球范围内影响着人类的健康。由于病毒感染的物种趋向性，动物模型往往不能反映生理状态。常规细胞系通常在遗传和表型上与原代细胞不同。建立体外生理模型来研究新兴病毒的感染，将有助于我们了解病毒与宿主细胞的相互作用，从而有利于抗病毒药物的发现。在目前的工作中，我们首先利用条件重编程(CR)和气液界面(ALI)技术在2D和3D培养系统中建立了正常的呼吸道上皮细胞(上、下呼吸道轨道)。这些长期培养的细胞保持分化潜能。更重要的是，这些细胞表达两种类型的流感病毒受体，α2-6-半乳糖和α2-3-半乳糖连接唾液酸，以及血管紧张素转换酶2(ACE2)，也是SARS冠状病毒的受体。这些细胞对大流行性流感H1N1(H1N1pdm)的感染是允许的。相比之下，肺癌细胞系A549和永生化的呼吸道上皮细胞(16HBE)对H1N1感染不敏感。在2D CRC培养上，病毒诱导的细胞病变效应(CPE)以时间依赖的方式发展。病理效应也容易观察到从3DALI培养的根尖层向基底层扩散。这种集成的2D CRC和3D ALI培养为研究新兴病毒的感染提供了一个生理学和个性化的体外模型。该模型可用于研究病毒生物学和宿主对病毒感染的反应，并可用于抗病毒药物的开发。
Infections of emerging and reemerging viruses (SARS-CoVs, influenza H1N1, etc.) largely and globally affect human health. Animal models often fail to reflect a physiological status because of species tropism of virus infection. Conventional cell lines are usually genetically and phenotypically different from primary cells. Developing an in vitro physiological model to study the infection of emerging viruses will facilitate our understanding of virus-host cell interactions, thereby benefiting antiviral drug discovery. In the current work, we first established normal airway epithelial cells (upper and lower airway track) in 2D and 3D culture systems using conditional reprogramming (CR) and air-liquid interface (ALI) techniques. These long-term cultures maintained differentiation potential. More importantly, these cells express two types of influenza virus receptors, α2-6-Gal- and α2-3-Gal-linked sialic acids, and angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoVs as well. These cells were permissive to the infection of pandemic influenza H1N1 (H1N1pdm). In contrast, the lung cancer cell line A549 and immortalized airway epithelial cells (16HBE) were not susceptible to H1N1 infection. A virus-induced cytopathic effect (CPE) on 2D CRC cultures developed in a time-dependent manner. The pathological effects were also readily observed spreading from the apical layer to the basal layer of the 3D ALI culture. This integrated 2D CRC and 3D ALI cultures provide a physiological and personalized in vitro model to study the infection of emerging viruses. This novel model can be used for studying virus biology and host response to viral infection and for antiviral drug discovery.
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影响因子：
4.8
作者：
Charoenvisal N;Keawcharoen J;Sreta D;Tantawet S;Jittimanee S;Arunorat J;Amonsin A;Thanawongnuwech R
通讯作者：
Thanawongnuwech R
影响因子：
3.7
作者：
Ding X;Lu J;Yu R;Wang X;Wang T;Dong F;Peng B;Wu W;Liu H;Geng Y;Zhang R;Ma H;Cheng J;Yu M;Fang S
通讯作者：
Fang S
DOI：
--
发表时间：
2012
期刊：
--
影响因子：
--
作者：
Xuefeng Liu;V. Ory;Sandra F Chapman;Hang Yuan;C. Albanese;B. Kallakury;O. Timofeeva;Caitlin M. Nealon;Aleksandra Dakić;V. Simić;B. Haddad;J. Rhim;A. Dritschilo;A. Riegel;A. McBride;R. Schlegel
通讯作者：
Xuefeng Liu;V. Ory;Sandra F Chapman;Hang Yuan;C. Albanese;B. Kallakury;O. Timofeeva;Caitlin M. Nealon;Aleksandra Dakić;V. Simić;B. Haddad;J. Rhim;A. Dritschilo;A. Riegel;A. McBride;R. Schlegel
影响因子：
5.4
作者：
Thompson, Catherine I.;Barclay, Wendy S.;Pickles, Raymond J.
通讯作者：
Pickles, Raymond J.
影响因子：
64.8
作者：
Imai, Masaki;Watanabe, Tokiko;Hatta, Masato;Das, Subash C.;Ozawa, Makoto;Shinya, Kyoko;Zhong, Gongxun;Hanson, Anthony;Katsura, Hiroaki;Watanabe, Shinji;Li, Chengjun;Kawakami, Eiryo;Yamada, Shinya;Kiso, Maki;Suzuki, Yasuo;Maher, Eileen A.;Neumann, Gabriele;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro