Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses.
Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses.
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DOI：
10.1016/j.cell.2020.12.004
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发表时间：
2021-01-07
期刊：
影响因子：
64.5
通讯作者：
Puschnik AS
中科院分区：
文献类型：
--
作者：
Wang R;Simoneau CR;Kulsuptrakul J;Bouhaddou M;Travisano KA;Hayashi JM;Carlson-Stevermer J;Zengel JR;Richards CM;Fozouni P;Oki J;Rodriguez L;Joehnk B;Walcott K;Holden K;Sil A;Carette JE;Krogan NJ;Ott M;Puschnik AS
冠状病毒科是一个病毒家族，可引起人类疾病，从轻度呼吸道感染到潜在致命的急性呼吸窘迫综合征。找到多种冠状病毒共有的宿主因子可以促进治疗方法的发展，以对抗当前和未来的冠状病毒大流行。在这里，我们在被SARS-CoV-2以及两种季节性流行的普通感冒冠状病毒OC 43和229 E感染的细胞中进行了全基因组CRISPR筛选。这种方法正确地鉴定了不同的病毒进入因子ACE 2（对于SARS-CoV-2），氨肽酶N（对于229 E）和糖胺聚糖（对于OC 43）。此外，我们确定磷脂酰肌醇磷酸生物合成和胆固醇稳态是支持所有三种冠状病毒感染的关键宿主途径。相比之下，溶酶体蛋白TMEM 106 B似乎是SARS-CoV-2感染所特有的。磷脂酰肌醇激酶和胆固醇稳态的药理学抑制减少了所有三种冠状病毒的复制。这些发现为理解冠状病毒生命周期和开发宿主导向疗法提供了重要见解。为了确定SARS-CoV-2和普通感冒冠状病毒OC 43和229 E感染所需的宿主因子，Wang et al.进行全基因组CRISPR敲除筛选。除了病毒特异性进入因子外，他们还发现了所有三种病毒感染所需的共同宿主途径，包括胆固醇稳态和磷脂酰肌醇激酶，并证明这些途径的药理学抑制表现出泛冠状病毒抗病毒活性。
The Coronaviridae are a family of viruses that cause disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach correctly identified the distinct viral entry factors ACE2 (for SARS-CoV-2), aminopeptidase N (for 229E), and glycosaminoglycans (for OC43). Additionally, we identified phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis as critical host pathways supporting infection by all three coronaviruses. By contrast, the lysosomal protein TMEM106B appeared unique to SARS-CoV-2 infection. Pharmacological inhibition of phosphatidylinositol kinases and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle and the development of host-directed therapies. To identify host factors required for the infection with SARS-CoV-2 and the common cold coronaviruses OC43 and 229E, Wang et al. conduct genome-wide CRISPR knockout screens. In addition to virus-specific entry factors, they uncover shared host pathways, including cholesterol homeostasis and phosphatidylinositol kinases, required for the infection with all three viruses and demonstrate that pharmacological inhibition of these pathways exhibits pan-coronavirus antiviral activity.
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影响因子：
64.5
作者：
Daniloski Z;Jordan TX;Wessels HH;Hoagland DA;Kasela S;Legut M;Maniatis S;Mimitou EP;Lu L;Geller E;Danziger O;Rosenberg BR;Phatnani H;Smibert P;Lappalainen T;tenOever BR;Sanjana NE
通讯作者：
Sanjana NE
DOI：
10.1534/g3.118.200144
发表时间：
2018-07-02
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Edie S;Zaghloul NA;Leitch CC;Klinedinst DK;Lebron J;Thole JF;McCallion AS;Katsanis N;Reeves RH
通讯作者：
Reeves RH
影响因子：
64.8
作者：
Fimia, Gian Maria;Stoykova, Anastassia;Cecconi, Francesco
通讯作者：
Cecconi, Francesco
影响因子：
64.5
作者：
Bouhaddou, Mehdi;Memon, Danish;Krogan, Nevan J.
通讯作者：
Krogan, Nevan J.
影响因子：
4.8
作者：
Charlton, Frank W.;Hover, Samantha;Mankouri, Jamel
通讯作者：
Mankouri, Jamel