Patterns of conserved gp120 epitope presentation on attached HIV-1 virions.
Patterns of conserved gp120 epitope presentation on attached HIV-1 virions.
复制标题
DOI：
10.1073/pnas.1705074114
复制
发表时间：
2017-11-14
影响因子：
11.1
通讯作者：
DeVico AL
中科院分区：
文献类型：
--
作者：
Mengistu M;Tang AH;Foulke JS Jr;Blanpied TA;Gonzalez MW;Spouge JL;Gallo RC;Lewis GK;DeVico AL
为了阐明通过体液免疫控制感染的各种选择，需要对艾滋病毒在早期复制期间的抗原性有一个完整的了解。HIV包膜蛋白gp120在宿主细胞附着过程中经历关键的结构重排，导致高度保守的表位暴露在病毒粒子表面。这些表位使Fc介导的抗病毒效应功能可能与HIV预防相关。在这里，我们使用3D超分辨率显微镜来展示gp120表位如何快速暴露在细胞-病毒界面的远端，从而引入了不受限制的抗体结合的机会。这些以前未被认识到的艾滋病毒抗原性方面进一步确定了逆转录病毒感染和免疫之间的关系，并应有助于开发以抗体为基础的艾滋病毒预防方法。需要全面了解艾滋病毒在早期复制过程中的抗原性，以阐明控制感染的各种选择。这些信息通常是通过分析分离的病毒包膜抗原、宿主CD4受体和同源抗体获得的。然而，通过先进的显微镜技术和试剂，直接检查病毒颗粒和病毒与细胞的相互作用现在是可能的。利用这些方法，我们最近确定了HIV表面抗原gp120中的CD4诱导(CD4i)过渡态表位，虽然不暴露在游离颗粒上，但在病毒与细胞结合时迅速产生免疫反应。在这里，我们使用3D直接随机光学重建显微镜(DSTORM)来显示某些针对过渡态结构的CD4i表位暴露在细胞结合的病毒粒子表面，从而解释了它们的免疫反应性。此外，这种结构和它们的标记表位分散在远离CD4接触的病毒粒子区域。我们进一步表明，CD4i暴露在远端的外观和位置部分依赖于GAG的成熟和病毒粒子内完整的基质-gp41相互作用。总而言之，这些观察为早期复制过程中的艾滋病毒提供了一个独特的视角。这些特征可以定义独特的见解，以了解体液反应如何针对病毒粒子，并开发相关的抗病毒对策。
A complete picture of HIV antigenicity during early replication is needed to elucidate the full range of options for controlling infection through humoral immunity. The HIV envelope protein, gp120, experiences key structural rearrangements during host cell attachment, leading to exposure of highly conserved epitopes on the virion surface. These epitopes enable Fc-mediated antiviral effector functions that may be relevant to HIV prevention. Here, we used 3D superresolution microscopy to show how gp120 epitopes are rapidly exposed distal to cell–virus interfaces, introducing the opportunity for unconstrained antibody binding. These previously unrecognized facets of HIV antigenicity further define relationships between retroviral infection and immunity and should facilitate the development of antibody-based approaches for HIV prevention. A complete picture of HIV antigenicity during early replication is needed to elucidate the full range of options for controlling infection. Such information is frequently gained through analyses of isolated viral envelope antigens, host CD4 receptors, and cognate antibodies. However, direct examination of viral particles and virus–cell interactions is now possible via advanced microscopy techniques and reagents. Using such methods, we recently determined that CD4-induced (CD4i) transition state epitopes in the HIV surface antigen, gp120, while not exposed on free particles, rapidly become immunoreactive upon virus–cell binding. Here, we use 3D direct stochastic optical reconstruction microscopy (dSTORM) to show that certain CD4i epitopes specific to transition state structures are exposed across the surface of cell-bound virions, thus explaining their immunoreactivity. Moreover, such structures and their marker epitopes are dispersed to regions of virions distal to CD4 contact. We further show that the appearance and positioning of distal CD4i exposures is partially dependent on Gag maturation and intact matrix–gp41 interactions within the virion. Collectively, these observations provide a unique perspective of HIV during early replication. These features may define unique insights for understanding how humoral responses target virions and for developing related antiviral countermeasures.
登录
查看更多内容
影响因子：
16.2
作者：
Dani, Adish;Huang, Bo;Bergan, Joseph;Dulac, Catherine;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
5.4
作者：
Acharya, Priyamvada;Tolbert, William D.;Pazgier, Marzena
通讯作者：
Pazgier, Marzena
DOI：
10.1073/pnas.1217609110
发表时间：
2013-01-02
影响因子：
11.1
作者：
Guan, Yongjun;Pazgier, Marzena;Lewis, George K.
通讯作者：
Lewis, George K.
影响因子：
4.8
作者：
Bennett, Adam;Liu, Jun;Subramaniam, Sriram
通讯作者：
Subramaniam, Sriram
影响因子：
5.4
作者：
Gonzalez, Mileidy W.;DeVico, Anthony L.;Spouge, John L.
通讯作者：
Spouge, John L.