Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection.
Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection.
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DOI：
10.1038/s41467-023-42610-x
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发表时间：
2023-10-28
影响因子：
16.6
通讯作者：
Bimczok, Diane
中科院分区：
文献类型：
--
作者：
Hashimi, Marziah;Sebrell, T. Andrew;Hedges, Jodi F.;Snyder, Deann;Lyon, Katrina N.;Byrum, Stephanie D.;Mackintosh, Samuel G.;Crowley, Dan;Cherne, Michelle D.;Skwarchuk, David;Robison, Amanda;Sidar, Barkan;Kunze, Anja;Loveday, Emma K.;Taylor, Matthew P.;Chang, Connie B.;Wilking, James N.;Walk, Seth T.;Schountz, Tony;Jutila, Mark A.;Bimczok, Diane
蝙蝠是几种人畜共患病病毒的天然宿主，这可能是由于它们控制病毒感染的能力增强。然而，蝙蝠抗病毒反应的机制还不清楚。在这里，我们建立了牙买加果蝠（JFB，Artibeus jamaicensis）肠道类器官严重急性呼吸综合征冠状病毒-2（SARS-CoV-2）感染模型。在感染SARS-CoV-2后，检测到病毒RNA和亚基因组RNA增加，但没有释放感染性病毒，表明JFB类器官仅支持有限的病毒复制，但不支持病毒繁殖。SARS-CoV-2复制与I型干扰素和炎性细胞因子的基因表达显著增加相关。有趣的是，SARS-CoV-2还引起JFB类器官的形成和生长增强。蛋白质组学揭示了炎症信号，细胞更新，细胞修复和SARS-CoV-2感染途径的增加。总的来说，我们的研究结果表明，原代JFB肠上皮细胞安装成功的抗病毒干扰素反应，SARS冠状病毒-2感染JFB细胞诱导保护性再生途径。蝙蝠是包括SARS-CoV-2在内的几种人畜共患病毒的天然宿主，因此需要更好地定义蝙蝠的抗病毒反应。在这里，Hashimi等人描述了蝙蝠肠道类器官中对SARS-CoV-2的抗病毒反应，发现诱导了干扰素和再生反应。
Bats are natural reservoirs for several zoonotic viruses, potentially due to an enhanced capacity to control viral infection. However, the mechanisms of antiviral responses in bats are poorly defined. Here we established a Jamaican fruit bat (JFB, Artibeus jamaicensis) intestinal organoid model of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Upon infection with SARS-CoV-2, increased viral RNA and subgenomic RNA was detected, but no infectious virus was released, indicating that JFB organoids support only limited viral replication but not viral reproduction. SARS-CoV-2 replication was associated with significantly increased gene expression of type I interferons and inflammatory cytokines. Interestingly, SARS-CoV-2 also caused enhanced formation and growth of JFB organoids. Proteomics revealed an increase in inflammatory signaling, cell turnover, cell repair, and SARS-CoV-2 infection pathways. Collectively, our findings suggest that primary JFB intestinal epithelial cells mount successful antiviral interferon responses and that SARS-CoV-2 infection in JFB cells induces protective regenerative pathways. Bats are natural reservoirs for several zoonotic viruses including SARS-CoV-2 thus there is a need to better define bat antiviral responses. Here, Hashimi et al. profile antiviral responses to SARS-CoV-2 in bat intestinal organoids finding that interferon and regenerative responses where induced.
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