Organization of cellular receptors into a nanoscale junction during HIV-1 adhesion.
Organization of cellular receptors into a nanoscale junction during HIV-1 adhesion.
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DOI：
10.1371/journal.pcbi.1000855
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发表时间：
2010-07-15
影响因子：
4.3
通讯作者：
Wirtz D
中科院分区：
文献类型：
--
作者：
Dobrowsky TM;Daniels BR;Siliciano RF;Sun SX;Wirtz D
1 型人类免疫缺陷病毒 (HIV-1) 与其宿主细胞的融合是新的抗逆转录病毒疗法的目标。病毒颗粒通过病毒表面蛋白 gp120 与柔性质膜相互作用，gp120 结合其主要细胞受体 CD4，随后结合辅助受体 CCR5。然而，这些受体是否以及如何在细胞和病毒颗粒之间的粘合连接处组织起来尚不清楚。在这里，随机模型预测，关于与 gp120 的结合，细胞受体 CD4 和 CCR5 在病毒粒子下方形成有组织的环状纳米级结构，该结构使质膜局部变形。细胞和病毒颗粒之间有组织的粘附连接，我们将其命名为病毒连接，让人想起充分表征的免疫突触，尽管长度尺度要小得多。在多种病理生理学相关条件下形成有组织的病毒连接可能代表了生产性感染的一个新的中间步骤。人类免疫缺陷病毒 (HIV) 进入细胞是预防 HIV 感染的新疗法的目标。虽然病毒进入的中间步骤已经被表征，但这些步骤之间的进展以及它们如何导致有效感染尚不清楚。通过使用随机模型，我们检查了单个病毒颗粒与填充有病毒受体的柔性质膜的初始相互作用。该模型预测病毒颗粒下方有组织的受体超微结构的形成，我们将其命名为病毒连接，这可能有助于有效的病毒感染。病毒连接的组织取决于受体密度、CD4键稳定性、膜机械灵活性以及病毒蛋白组织和密度。
The fusion of the human immunodeficiency virus type 1 (HIV-1) with its host cell is the target for new antiretroviral therapies. Viral particles interact with the flexible plasma membrane via viral surface protein gp120 which binds its primary cellular receptor CD4 and subsequently the coreceptor CCR5. However, whether and how these receptors become organized at the adhesive junction between cell and virion are unknown. Here, stochastic modeling predicts that, regarding binding to gp120, cellular receptors CD4 and CCR5 form an organized, ring-like, nanoscale structure beneath the virion, which locally deforms the plasma membrane. This organized adhesive junction between cell and virion, which we name the viral junction, is reminiscent of the well-characterized immunological synapse, albeit at much smaller length scales. The formation of an organized viral junction under multiple physiopathologically relevant conditions may represent a novel intermediate step in productive infection. The entry of human immunodeficiency virus (HIV) into cells is the target for new therapies preventing HIV infection. While intermediate steps of viral entry have been characterized, the progression between these steps and how they result in productive infection are not well understood. By using stochastic modeling, we examine the initial interaction of a single viral particle with a flexible plasma membrane populated with viral receptors. The model predicts the formation of an organized receptor ultrastructure beneath the viral particle, which we name viral junction and which may contribute to productive viral infection. The organization of the viral junction depends on receptor density, CD4 bond stability, membrane mechanical flexibility, as well as viral protein organization and density.
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影响因子：
64.8
作者：
Liu, Jun;Bartesaghi, Alberto;Borgnia, Mario J.;Sapiro, Guillermo;Subramaniam, Sriram
通讯作者：
Subramaniam, Sriram
影响因子：
2.2
作者：
Liu, SQ;Fan, SX;Sun, ZR
通讯作者：
Sun, ZR
影响因子：
21.3
作者：
Jimenez-Baranda, Sonia;Gomez-Mouton, Concepcion;Manes, Santos
通讯作者：
Manes, Santos
影响因子：
3.4
作者：
Atilgan, E;Wirtz, D;Sun, SX
通讯作者：
Sun, SX
影响因子：
2.9
作者：
Gallo, SA;Puri, A;Blumenthal, R
通讯作者：
Blumenthal, R