Forschungsschwerpunkt Infektion und Krebs, F020, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Retrovirology. 2010 May 12;7:43. doi: 10.1186/1742-4690-7-43.
Mutant HIV (HIV-Env-Tr712) lacking the cytoplasmic tail of the viral glycoprotein (Env-CT) exhibits a cell-type specific replication phenotype such that replicative spread occurs in some T-cell lines (referred to as permissive cells) but fails to do so in most T-cell lines or in PBMCs (referred to as non-permissive cells). We aim to gain insight on the underlying requirement for the Env-CT for viral spread in non-permissive cells.
We established that in comparison to HIV-Wt, both cell-free and cell-to-cell transmission of mutant HIV-Env-Tr712 from non-permissive cells were severely impaired under naturally low infection conditions. This requirement for Env-CT could be largely overcome by using saturating amounts of virus for infection. We further observed that in permissive cells, which supported both routes of mutant virus transmission, viral gene expression levels, Gag processing and particle release were inherently higher than in non-permissive cells, a factor which may be significantly contributing to their permissivity phenotype. Additionally, and correlating with viral transfer efficiencies in these cell types, HIV-Gag accumulation at the virological synapse (VS) was reduced to background levels in the absence of the Env-CT in conjugates of non-permissive cells but not in permissive cells.
During natural infection conditions, the HIV-Env-CT is critically required for viral transmission in cultures of non-permissive cells by both cell-free and cell-to-cell routes and is instrumental for Gag accumulation to the VS. The requirement of the Env-CT for these related processes is abrogated in permissive cells, which exhibit higher HIV gene expression levels.
缺乏病毒糖蛋白（Env-CT）细胞质尾巴的突变 HIV（HIV-Env-Tr712）表现出细胞类型特异性复制表型，使得复制在一些 T 细胞系（称为允许细胞）中传播，但在大多数 T 细胞系或 PBMC 中不能传播（称为非允许细胞）。我们旨在深入了解 Env-CT 对非允许细胞中病毒传播的基本要求。
我们发现，与 HIV-Wt 相比，突变 HIV-Env-Tr712 的无细胞和细胞间传播在自然低感染条件下从非允许细胞中严重受损。通过使用饱和量的病毒进行感染，可以在很大程度上克服对 Env-CT 的这种需求。我们还观察到，在允许细胞中，突变病毒的两种传播途径都得到支持，病毒基因表达水平、Gag 加工和颗粒释放都比非允许细胞固有更高，这一因素可能对其允许表型有显著贡献。此外，与这些细胞类型中的病毒转移效率相关，在非允许细胞的共轭物中缺乏 Env-CT 时，病毒 Gag 在病毒学突触（VS）处的积累减少到背景水平，但在允许细胞中则不会。
在自然感染条件下，HIV-Env-CT 在非允许细胞的无细胞和细胞间途径中对病毒的传播至关重要，并且对于 Gag 积累到 VS 至关重要。在允许细胞中，这些相关过程对 Env-CT 的需求被消除，这些细胞表现出更高的 HIV 基因表达水平。
