CD164 is a host factor for lymphocytic choriomeningitis virus entry.
CD164 is a host factor for lymphocytic choriomeningitis virus entry.
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DOI：
10.1073/pnas.2119676119
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发表时间：
2022-03-08
影响因子：
11.1
通讯作者：
Whelan SPJ
中科院分区：
文献类型：
--
作者：
Bakkers MJG;Moon-Walker A;Herlo R;Brusic V;Stubbs SH;Hastie KM;Saphire EO;Kirchhausen TL;Whelan SPJ
淋巴细胞性脉络丛脑膜炎病毒（LCMV）是沙粒病毒的原型，几十年来一直被用作了解宿主对病毒感染的免疫反应的模型。LCMV感染可导致免疫功能低下的人致命的脑膜炎，并可导致先天性出生缺陷和自然流产，如果在怀孕期间获得。使用遗传筛选，我们发现了参与LCMV进入的宿主因素，这些因素以前是未知的，并且是对抗LCMV感染的候选治疗靶点。这项研究扩展了我们对LCMV进入途径的理解，揭示了其糖蛋白从利用质膜上的已知受体α-DG和硫酸乙酰肝素转变为在内溶酶体隔室中发现的pH水平下结合溶酶体粘蛋白CD 164，促进膜融合。淋巴细胞性脉络丛脑膜炎病毒（LCMV）是一种啮齿动物传播的人畜共患沙粒病毒，可导致先天性畸形，对移植受体可能是致命的。使用全基因组功能丧失筛选，我们确定LCMV进入细胞所需的宿主因子。我们鉴定了溶酶体粘蛋白CD 164、糖基化因子、硫酸乙酰肝素生物合成机制和已知受体α-肌营养不良聚糖（α-DG）。生化分析显示，LCMV糖蛋白在酸性pH下结合CD 164，并且需要残基N104处的唾液酸化聚糖。我们证明，LCMV进入通过在膜融合之前将细胞膜上的硫酸乙酰肝素或α-DG转换为CD 164的病毒结合进行，从而确定了治疗干预的其他潜在靶点。
Lymphocytic choriomeningitis virus (LCMV) is the prototypic arenavirus and has been utilized for decades as a model to understand the host immune response against viral infection. LCMV infection can lead to fatal meningitis in immunocompromised people and can lead to congenital birth defects and spontaneous abortion if acquired during pregnancy. Using a genetic screen, we uncover host factors involved in LCMV entry that were previously unknown and are candidate therapeutic targets to combat LCMV infection. This study expands our understanding of the entry pathway of LCMV, revealing that its glycoprotein switches from utilizing the known receptor α-DG and heparan sulfate at the plasma membrane to binding the lysosomal mucin CD164 at pH levels found in endolysosomal compartments, facilitating membrane fusion. Lymphocytic choriomeningitis virus (LCMV) is a rodent-borne zoonotic arenavirus that causes congenital abnormalities and can be fatal for transplant recipients. Using a genome-wide loss-of-function screen, we identify host factors required for LCMV entry into cells. We identify the lysosomal mucin CD164, glycosylation factors, the heparan sulfate biosynthesis machinery, and the known receptor alpha-dystroglycan (α-DG). Biochemical analysis revealed that the LCMV glycoprotein binds CD164 at acidic pH and requires a sialylated glycan at residue N104. We demonstrate that LCMV entry proceeds by the virus switching binding from heparan sulfate or α-DG at the plasma membrane to CD164 prior to membrane fusion, thus identifying additional potential targets for therapeutic intervention.
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影响因子：
64.8
作者：
Cote, Marceline;Misasi, John;Ren, Tao;Bruchez, Anna;Lee, Kyungae;Filone, Claire Marie;Hensley, Lisa;Li, Qi;Ory, Daniel;Chandran, Kartik;Cunningham, James
通讯作者：
Cunningham, James
影响因子：
46.9
作者：
Doench JG;Fusi N;Sullender M;Hegde M;Vaimberg EW;Donovan KF;Smith I;Tothova Z;Wilen C;Orchard R;Virgin HW;Listgarten J;Root DE
通讯作者：
Root DE
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6.7
作者：
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通讯作者：
Choe, Hyeryun
影响因子：
3.7
作者：
Burri, Dominique J.;Pasquato, Antonella;Kunz, Stefan
通讯作者：
Kunz, Stefan
影响因子：
28.3
作者：
Cohen-Dvashi, Hadas;Kilimnik, Itay;Diskin, Ron
通讯作者：
Diskin, Ron