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HIV-1 capsid exploitation of the host microtubule cytoskeleton during early infection
Retrovirology ( IF 2.7 ) Pub Date : 2021-07-06 , DOI: 10.1186/s12977-021-00563-3
Mojgan H Naghavi 1
Affiliation  

Microtubules (MTs) form a filamentous array that provide both structural support and a coordinated system for the movement and organization of macromolecular cargos within the cell. As such, they play a critical role in regulating a wide range of cellular processes, from cell shape and motility to cell polarization and division. The array is radial with filament minus-ends anchored at perinuclear MT-organizing centers and filament plus-ends continuously growing and shrinking to explore and adapt to the intracellular environment. In response to environmental cues, a small subset of these highly dynamic MTs can become stabilized, acquire post-translational modifications and act as specialized tracks for cargo trafficking. MT dynamics and stability are regulated by a subset of highly specialized MT plus-end tracking proteins, known as +TIPs. Central to this is the end-binding (EB) family of proteins which specifically recognize and track growing MT plus-ends to both regulate MT polymerization directly and to mediate the accumulation of a diverse array of other +TIPs at MT ends. Moreover, interaction of EB1 and +TIPs with actin-MT cross-linking factors coordinate changes in actin and MT dynamics at the cell periphery, as well as during the transition of cargos from one network to the other. The inherent structural polarity of MTs is sensed by specialized motor proteins. In general, dynein directs trafficking of cargos towards the minus-end while most kinesins direct movement toward the plus-end. As a pathogenic cargo, HIV-1 uses the actin cytoskeleton for short-range transport most frequently at the cell periphery during entry before transiting to MTs for long-range transport to reach the nucleus. While the fundamental importance of MT networks to HIV-1 replication has long been known, recent work has begun to reveal the underlying mechanistic details by which HIV-1 engages MTs after entry into the cell. This includes mimicry of EB1 by capsid (CA) and adaptor-mediated engagement of dynein and kinesin motors to elegantly coordinate early steps in infection that include MT stabilization, uncoating (conical CA disassembly) and virus transport toward the nucleus. This review discusses recent advances in our understanding of how MT regulators and their associated motors are exploited by incoming HIV-1 capsid during early stages of infection.

中文翻译:

HIV-1衣壳在早期感染期间对宿主微管细胞骨架的利用

微管 (MT) 形成丝状阵列,为细胞内大分子货物的运动和组织提供结构支持和协调系统。因此,它们在调节广泛的细胞过程中发挥着关键作用,从细胞形状和运动到细胞极化和分裂。该阵列呈放射状,细丝负端锚定在核周 MT 组织中心,细丝正端不断增长和收缩,以探索和适应细胞内环境。为响应环境线索,这些高度动态的 MT 中的一小部分可以变得稳定,获得翻译后修饰并充当货物运输的专门轨道。MT 动力学和稳定性受高度专业化的 MT 加端跟踪蛋白子集(称为 +TIP)的调节。其核心是末端结合 (EB) 蛋白质家族,它特异性识别和跟踪不断增长的 MT 正端,既直接调节 MT 聚合,又介导 MT 末端各种其他 +TIP 的积累。此外,EB1 和 +TIP 与肌动蛋白-MT 交联因子的相互作用协调了细胞外围的肌动蛋白和 MT 动力学的变化,以及在货物从一个网络到另一个网络的过渡期间。MTs 的固有结构极性由专门的运动蛋白感知。一般来说,动力蛋白将货物的运输导向负端,而大多数驱动蛋白则将运动导向正端。作为致病货物,HIV-1 使用肌动蛋白细胞骨架在进入期间最频繁地在细胞外围进行短程运输,然后转移到 MT 进行长程运输以到达细胞核。虽然 MT 网络对 HIV-1 复制的根本重要性早已为人所知,但最近的工作已开始揭示 HIV-1 在进入细胞后与 MT 结合的潜在机制细节。这包括衣壳 (CA) 对 EB1 的模仿,以及适配器介导的动力蛋白和驱动蛋白马达的参与,以优雅地协调感染的早期步骤,包括 MT 稳定、脱壳(锥形 CA 拆卸)和病毒向细胞核的转运。本综述讨论了我们对 MT 调节器及其相关电机如何在感染的早期阶段被传入的 HIV-1 衣壳利用的最新进展。虽然 MT 网络对 HIV-1 复制的根本重要性早已为人所知,但最近的工作已开始揭示 HIV-1 在进入细胞后与 MT 结合的潜在机制细节。这包括衣壳 (CA) 对 EB1 的模仿,以及适配器介导的动力蛋白和驱动蛋白马达的参与,以优雅地协调感染的早期步骤,包括 MT 稳定、脱壳(锥形 CA 拆卸)和病毒向细胞核的转运。本综述讨论了我们对 MT 调节器及其相关电机如何在感染的早期阶段被传入的 HIV-1 衣壳利用的最新进展。虽然 MT 网络对 HIV-1 复制的根本重要性早已为人所知,但最近的工作已开始揭示 HIV-1 在进入细胞后与 MT 结合的潜在机制细节。这包括衣壳 (CA) 对 EB1 的模仿,以及适配器介导的动力蛋白和驱动蛋白马达的参与,以优雅地协调感染的早期步骤,包括 MT 稳定、脱壳(锥形 CA 拆卸)和病毒向细胞核的转运。本综述讨论了我们对 MT 调节器及其相关电机如何在感染的早期阶段被传入的 HIV-1 衣壳利用的最新进展。这包括衣壳 (CA) 对 EB1 的模仿,以及适配器介导的动力蛋白和驱动蛋白马达的参与,以优雅地协调感染的早期步骤,包括 MT 稳定、脱壳(锥形 CA 拆卸)和病毒向细胞核的转运。本综述讨论了我们对 MT 调节器及其相关电机如何在感染的早期阶段被传入的 HIV-1 衣壳利用的最新进展。这包括衣壳 (CA) 对 EB1 的模仿,以及适配器介导的动力蛋白和驱动蛋白马达的参与,以优雅地协调感染的早期步骤,包括 MT 稳定、脱壳(锥形 CA 拆卸)和病毒向细胞核的转运。本综述讨论了我们对 MT 调节器及其相关电机如何在感染的早期阶段被传入的 HIV-1 衣壳利用的最新进展。
更新日期:2021-07-06
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