Lehmann-Che Jacqueline, Renault Noémie, Giron Marie Lou, Roingeard Philippe, Clave Emmanuel, Tobaly-Tapiero Joelle, Bittoun Patricia, Toubert Antoine, de Thé Hugues, Saïb Ali
Université Paris 7, Paris, France.
PLoS Pathog. 2007 May 25;3(5):e74. doi: 10.1371/journal.ppat.0030074.
Completion of early stages of retrovirus infection depends on the cell cycle. While gammaretroviruses require mitosis for proviral integration, lentiviruses are able to replicate in post-mitotic non-dividing cells. Resting cells such as naive resting T lymphocytes from peripheral blood cannot be productively infected by retroviruses, including lentiviruses, but the molecular basis of this restriction remains poorly understood. We demonstrate that in G0 resting cells (primary fibroblasts or peripheral T cells), incoming foamy retroviruses accumulate in close proximity to the centrosome, where they lie as structured and assembled capsids for several weeks. Under these settings, virus uncoating is impaired, but upon cell stimulation, Gag proteolysis and capsid disassembly occur, which allows viral infection to proceed. The data imply that foamy virus uncoating is the rate-limiting step for productive infection of primary G0 cells. Incoming foamy retroviruses can stably persist at the centrosome, awaiting cell stimulation to initiate capsid cleavage, nuclear import, and viral gene expression.
逆转录病毒感染早期阶段的完成取决于细胞周期。γ逆转录病毒需要有丝分裂才能进行前病毒整合，而慢病毒能够在有丝分裂后不分裂的细胞中复制。外周血中未经激活的静止T淋巴细胞等静止细胞不能被包括慢病毒在内的逆转录病毒有效感染，但其限制的分子基础仍知之甚少。我们证明，在G0期静止细胞（原代成纤维细胞或外周T细胞）中，进入的泡沫逆转录病毒聚集在中心体附近，以有结构且组装好的衣壳形式存在数周。在这些情况下，病毒脱壳受损，但细胞受到刺激后，Gag蛋白水解和衣壳解体发生，从而使病毒感染得以继续。数据表明，泡沫病毒脱壳是原代G0细胞有效感染的限速步骤。进入的泡沫逆转录病毒可以在中心体稳定持续存在，等待细胞刺激以启动衣壳裂解、核输入和病毒基因表达。
