Bats as a model to understand the evolution of coronavirus-host interactions
蝙蝠作为了解冠状病毒与宿主相互作用进化的模型
基本信息
- 批准号:RGPIN-2022-03010
- 负责人:
- 金额:$ 2.7万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2022
- 资助国家:加拿大
- 起止时间:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Bats play important ecological roles and perform critical functions such as pollination, seed dispersal and pest control. However, recent studies have identified that bats are reservoirs of emerging viruses that causes severe and often fatal disease in livestock and humans. These include ebola and Marburg filoviruses, Nipah and Hendra paramyxoviruses and a diverse range of coronaviruses, such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, porcine epidemic diarrhea virus (PEDV) and swine acute diarrhea syndrome coronavirus (SADS-CoV). Interestingly, bats that are naturally or experimentally infected with these viruses do not develop apparent signs of infection or disease. Thus, bats provide an intriguing model to study virus-host interactions. As part of our NSERC Discovery proposal, we aim to establish a long-term research program to study how bat immune systems have evolved to better tolerate infections with emerging viruses that cause severe disease in livestock and humans. We shall study how viruses, such as MERS-CoV, SARS-CoV-2 and bona fide bat borne coronaviruses interact with bat cells and identify protective antiviral factors that are produced by bat cells upon virus infection. Preliminary data from our work suggest that upon virus infection, bat cells induce the expression of novel antiviral genes that are not upregulated in infected human cells, which led us to hypothesize that bats have evolved novel antiviral molecules and processes that are distinct from other mammals. We shall use high throughput approaches to identify differentially expressed genes in infected bat cells. We shall characterize cellular processes and protein-protein interactions that come together to harmoniously execute their antiviral effects in bat cells. Finally, we shall functionally characterize the protective effects of bat antiviral proteins using Eptesicus fuscus bats. Our laboratory (in vitro) to animal model (in vivo) characterization will enable robust identification of molecular factors that have evolved in bats to control virus replication without developing disease. Our study will inform the identification and development of novel therapeutic molecules or drug targets in livestock species and humans to control infections with bat borne viruses, such as coronaviruses. In addition, our research will shed light on molecular factors that regulate virus replication in bats and thus identify critical immunological checkpoints that control virus spill over from bats to other mammals. Knowledge gained from our studies will inform national and global policies around emerging zoonotic diseases. Eptesicus fuscus bats are native to Canada and are naturally persistently infected with a bat coronavirus. Thus, our research outcomes will directly affect Canadian agricultural and wildlife sectors, while also positioning Canada as a world leader in research on bats and bat immunology.
蝙蝠扮演着重要的生态角色,并发挥着重要的功能,如授粉,种子传播和害虫控制。然而,最近的研究发现,蝙蝠是新出现的病毒的宿主,这些病毒在牲畜和人类中引起严重且往往致命的疾病。这些病毒包括埃博拉病毒和马尔堡丝状病毒、尼帕病毒和亨德拉副粘病毒以及各种冠状病毒,如中东呼吸综合征冠状病毒、严重急性呼吸综合征冠状病毒、SARS-CoV-2、猪流行性腹泻病毒和猪急性腹泻综合征冠状病毒。有趣的是,自然或实验感染这些病毒的蝙蝠不会出现明显的感染或疾病迹象。因此,蝙蝠提供了一个有趣的模型来研究病毒与宿主的相互作用。作为我们NSERC发现提案的一部分,我们的目标是建立一个长期的研究计划,研究蝙蝠免疫系统如何进化,以更好地耐受导致牲畜和人类严重疾病的新病毒感染。我们将研究病毒,如MERS-CoV,SARS-CoV-2和真正的蝙蝠传播的冠状病毒如何与蝙蝠细胞相互作用,并确定病毒感染后蝙蝠细胞产生的保护性抗病毒因子。我们工作的初步数据表明,在病毒感染后,蝙蝠细胞诱导新的抗病毒基因的表达,这些基因在感染的人类细胞中不上调,这使我们假设蝙蝠已经进化出了与其他哺乳动物不同的新的抗病毒分子和过程。我们将使用高通量的方法来确定差异表达的基因在感染蝙蝠细胞。我们将描述细胞过程和蛋白质-蛋白质相互作用,这些过程和蛋白质-蛋白质相互作用在蝙蝠细胞中和谐地执行其抗病毒作用。最后,我们将在功能上表征蝙蝠抗病毒蛋白的保护作用,使用棕蝠。我们的实验室(体外)到动物模型(体内)的表征将使蝙蝠中进化的分子因子能够可靠地鉴定,以控制病毒复制而不发生疾病。 我们的研究将为牲畜和人类中新型治疗分子或药物靶点的识别和开发提供信息,以控制蝙蝠传播病毒(例如冠状病毒)的感染。此外,我们的研究将揭示调节蝙蝠中病毒复制的分子因素,从而确定控制病毒从蝙蝠传播到其他哺乳动物的关键免疫检查点。从我们的研究中获得的知识将为国家和全球关于新出现的人畜共患病的政策提供信息。棕棕蝠原产于加拿大,自然持续感染蝙蝠冠状病毒。因此,我们的研究成果将直接影响加拿大的农业和野生动物部门,同时也将加拿大定位为蝙蝠和蝙蝠免疫学研究的世界领导者。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Banerjee, Arinjay其他文献
Generation and Characterization of Eptesicus fuscus (Big brown bat) kidney cell lines immortalized using the Myotis polyomavirus large T-antigen
- DOI:
10.1016/j.jviromet.2016.09.008 - 发表时间:
2016-11-01 - 期刊:
- 影响因子:3.1
- 作者:
Banerjee, Arinjay;Rapin, Noreen;Misra, Vikram - 通讯作者:
Misra, Vikram
Two DNA vaccines protect against severe disease and pathology due to SARS-CoV-2 in Syrian hamsters.
- DOI:
10.1038/s41541-022-00461-5 - 发表时间:
2022-04-26 - 期刊:
- 影响因子:9.2
- 作者:
Babuadze, George Giorgi;Fausther-Bovendo, Hugues;deLaVega, Marc-Antoine;Lillie, Brandon;Naghibosadat, Maedeh;Shahhosseini, Nariman;Joyce, Michael A.;Saffran, Holly A.;Lorne Tyrrell, D.;Falzarano, Darryl;Senthilkumaran, Chandrika;Christie-Holmes, Natasha;Ahn, Steven;Gray-Owen, Scott D.;Banerjee, Arinjay;Mubareka, Samira;Mossman, Karen;Dupont, Chanel;Pedersen, Jannie;Lafrance, Mark-Alexandre;Kobinger, Gary P.;Kozak, Robert - 通讯作者:
Kozak, Robert
Coupling field and laboratory studies of immunity and infection in zoonotic hosts.
- DOI:
10.1016/s2666-5247(23)00032-0 - 发表时间:
2023-05 - 期刊:
- 影响因子:38.2
- 作者:
Becker, Daniel J.;Banerjee, Arinjay - 通讯作者:
Banerjee, Arinjay
Intronic regulation of SARS-CoV-2 receptor (ACE2) expression mediated by immune signaling and oxidative stress pathways.
- DOI:
10.1016/j.isci.2022.104614 - 发表时间:
2022-07-15 - 期刊:
- 影响因子:5.8
- 作者:
Richard, Daniel;Muthuirulan, Pushpanathan;Aguiar, Jennifer;Doxey, Andrew C.;Banerjee, Arinjay;Mossman, Karen;Hirota, Jeremy;Capellini, Terence D. - 通讯作者:
Capellini, Terence D.
SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia.
- DOI:
10.1016/j.redox.2022.102508 - 发表时间:
2022-12 - 期刊:
- 影响因子:11.4
- 作者:
Archer, Stephen L.;Dasgupta, Asish;Chen, Kuang-Hueih;Wu, Danchen;Baid, Kaushal;Mamatis, John E.;Gonzalez, Victoria;Read, Austin;Bentley, Rachel ET.;Martin, Ashley Y.;Mewburn, Jeffrey D.;Dunham-Snary, Kimberly J.;Evans, Gerald A.;Levy, Gary;Jones, Oliver;Al-Qazazi, Ruaa;Ring, Brooke;Alizadeh, Elahe;Hindmarch, Charles CT.;Rossi, Jenna;Lima, Patricia DA.;Falzarano, Darryl;Banerjee, Arinjay;Colpitts, Che C. - 通讯作者:
Colpitts, Che C.
Banerjee, Arinjay的其他文献
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{{ truncateString('Banerjee, Arinjay', 18)}}的其他基金
Bats as a model to understand the evolution of coronavirus-host interactions
蝙蝠作为了解冠状病毒与宿主相互作用进化的模型
- 批准号:
DGECR-2022-00168 - 财政年份:2022
- 资助金额:
$ 2.7万 - 项目类别:
Discovery Launch Supplement
Evolution of virus-host interactions in bats
蝙蝠病毒与宿主相互作用的进化
- 批准号:
532117-2019 - 财政年份:2020
- 资助金额:
$ 2.7万 - 项目类别:
Postdoctoral Fellowships
Evolution of virus-host interactions in bats
蝙蝠病毒与宿主相互作用的进化
- 批准号:
532117-2019 - 财政年份:2019
- 资助金额:
$ 2.7万 - 项目类别:
Postdoctoral Fellowships
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