HIV-1 Envelope Glycoprotein Cell Surface Localization Is Associated with Antibody-Induced Internalization.
HIV-1 Envelope Glycoprotein Cell Surface Localization Is Associated with Antibody-Induced Internalization.
复制标题
DOI：
10.3390/v13101953
复制
发表时间：
2021-09-29
期刊：
影响因子：
--
通讯作者：
Finzi A
中科院分区：
文献类型：
--
作者：
Anand SP;Prévost J;Descôteaux-Dinelle J;Richard J;Nguyen DN;Medjahed H;Chen HC;Smith AB 3rd;Pazgier M;Finzi A
为了最大限度地减少针对受感染细胞的免疫反应，HIV-1 进化出了不同的机制来限制其包膜糖蛋白 (Env) 的表面表达。最近的观察表明，某些针对 Env“闭合”构象的广泛中和抗体（bNAb）的结合会诱导其内化。另一方面，优先靶向“开放”构象的 Env 的非中和抗体 (nNAb) 会在较长时间内与细胞表面的 Env 结合。在这项研究中，我们试图更好地了解抗体介导的 Env 内化率差异背后的潜在机制。我们证明，使用 CD4 模拟物“强制”打开 Env 允许 nNAb 结合，并导致 Env 内化率与 bNAb 结合时观察到的相似。此外，我们可以识别不同的 Env 群体，它们被 Abs 差异靶向，从而介导更快的内化速度，这表明抗体诱导的 Env 内化机制部分取决于 Env 在细胞表面的定位。
To minimize immune responses against infected cells, HIV-1 has evolved different mechanisms to limit the surface expression of its envelope glycoproteins (Env). Recent observations suggest that the binding of certain broadly neutralizing antibodies (bNAbs) targeting the ‘closed’ conformation of Env induces its internalization. On the other hand, non-neutralizing antibodies (nNAbs) that preferentially target Env in its ‘open’ conformation, remain bound to Env on the cell surface for longer periods of time. In this study, we attempt to better understand the underlying mechanisms behind the differential rates of antibody-mediated Env internalization. We demonstrate that ‘forcing’ open Env using CD4 mimetics allows for nNAb binding and results in similar rates of Env internalization as those observed upon the bNAb binding. Moreover, we can identify distinct populations of Env that are differentially targeted by Abs that mediate faster rates of internalization, suggesting that the mechanism of antibody-induced Env internalization partially depends on the localization of Env on the cell surface.
登录
查看更多内容
影响因子：
4.1
作者：
Laumaea A;Smith AB 3rd;Sodroski J;Finzi A
通讯作者：
Finzi A
影响因子：
4.2
作者：
Melillo, Bruno;Liang, Shuaiyi;Smith, Amos B., III
通讯作者：
Smith, Amos B., III
影响因子：
64.8
作者：
OBRIEN, WA;KOYANAGI, Y;CHEN, ISY
通讯作者：
CHEN, ISY
影响因子：
5.4
作者：
Haim, Hillel;Salas, Ignacio;Sodroski, Joseph
通讯作者：
Sodroski, Joseph
影响因子：
11.1
作者：
Richard J;Veillette M;Ding S;Zoubchenok D;Alsahafi N;Coutu M;Brassard N;Park J;Courter JR;Melillo B;Smith AB 3rd;Shaw GM;Hahn BH;Sodroski J;Kaufmann DE;Finzi A
通讯作者：
Finzi A