Viral Size Modulates Sendai Virus Binding to Cholesterol-Stabilized Receptor Nanoclusters.
Viral Size Modulates Sendai Virus Binding to Cholesterol-Stabilized Receptor Nanoclusters.
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DOI：
10.1021/acs.jpcb.2c03830
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发表时间：
2022-09-15
影响因子：
3.3
通讯作者：
Rawle, Robert J.
中科院分区：
文献类型：
--
作者：
Lam, Amy;Yuan, Daniel S.;Ahmed, Samir H.;Rawle, Robert J.
与宿主膜结合是动物病毒感染的初始步骤。仙台病毒（SeV）是这里研究的模型呼吸道病毒，利用唾液酸缀合的糖蛋白和糖脂作为结合受体。在之前的一份研究单一病毒与支持的脂质双层 (SLB) 结合的报告中，我们发现 SeV 和甲型流感病毒（毒株 X31、IAVX31）的结合之间存在令人费解的机制差异。两种病毒都使用相似的受体并表现出相似的协同结合行为，但 IAVX31 的结合会受到 SLB 胆固醇浓度的改变，SLB 胆固醇浓度可以稳定受体纳米簇，而 SeV 则不然。在这里，我们认为病毒大小分布的差异可以解释这种差异；病毒大小可能会改变接触区域中病毒与受体相互作用的数量，从而改变对受体纳米簇的敏感性。为了测试这一点，我们比较了尺寸过滤和未过滤的 SeV 之间 SeV 结合对 SLB 胆固醇浓度的依赖性。在高受体密度下，未过滤的病毒几乎没有表现出依赖性，但大小过滤的病毒表现出线性胆固醇依赖性，类似于IAVX31。然而，在低受体密度下，未过滤的病毒确实表现出胆固醇依赖性，表明只有当潜在的病毒-受体相互作用的数量足够小时，受体纳米簇才会增强病毒结合。我们还研究了病毒大小和受体纳米簇对结合后病毒迁移性的影响。虽然病毒大小的差异极大地影响了流动性，但受体纳米簇对流动性的影响很小。总之，我们的结果强调了病毒感染中病毒大小分布和受体横向分布的机制显着性。
Binding to the host membrane is the initial infection step for animal viruses. Sendai virus (SeV), the model respirovirus studied here, utilizes sialic-acid-conjugated glycoproteins and glycolipids as receptors for binding. In a previous report studying single virus binding to supported lipid bilayers (SLBs), we found a puzzling mechanistic difference between the binding of SeV and influenza A virus (strain X31, IAVX31). Both viruses use similar receptors and exhibit similar cooperative binding behavior, but whereas IAVX31 binding was altered by SLB cholesterol concentration, which can stabilize receptor nanoclusters, SeV was not. Here, we propose that differences in viral size distributions can explain this discrepancy; viral size could alter the number of virus–receptor interactions in the contact area and, therefore, the sensitivity to receptor nanoclusters. To test this, we compared the dependence of SeV binding on SLB cholesterol concentration between size-filtered and unfiltered SeV. At high receptor density, the unfiltered virus showed little dependence, but the size-filtered virus exhibited a linear cholesterol dependence, similar to IAVX31. However, at low receptor densities, the unfiltered virus did exhibit a cholesterol dependence, indicating that receptor nanoclusters enhance viral binding only when the number of potential virus–receptor interactions is small enough. We also studied the influence of viral size and receptor nanoclusters on viral mobility following binding. Whereas differences in viral size greatly influenced mobility, the effect of receptor nanoclusters on mobility was small. Together, our results highlight the mechanistic salience of both the distribution of viral sizes and the lateral distribution of receptors in a viral infection.
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影响因子：
15
作者：
Shi, Jinjun;Yang, Tinglu;Cremer, Paul S.
通讯作者：
Cremer, Paul S.
DOI：
10.1073/pnas.77.4.1947
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
HOLMGREN, J;SVENNERHOLM, L;STRANNEGARD, O
通讯作者：
STRANNEGARD, O
影响因子：
3.4
作者：
Rawle, Robert J.;Giraldo, Ana M. Villamil;Kasson, Peter M.
通讯作者：
Kasson, Peter M.
影响因子：
6.7
作者：
Sieben, Christian;Sezgin, Erdinc;Manley, Suliana
通讯作者：
Manley, Suliana
影响因子：
56.9
作者：
Sackmann, E
通讯作者：
Sackmann, E