Prochasson Léa, Mghezzi-Habellah Makram, Roisin Armelle, Palma Martine, Robin Jean-Philippe, de Bossoreille Stève, Cluet David, Mouelhi Malèke, Decimo Didier, Desrames Alexandra, Chaze Thibault, Matondo Mariette, Dutartre Hélène, Thoulouze Maria-Isabel, Lejeune Fabrice, Jalinot Pierre, Rety Stephane, Mocquet Vincent
Laboratoire de Biologie et Modélisation de la Cellule, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, Inserm U1293, CNRS UMR5239, F-69364 Lyon, France.
Université de Lille, CNRS, Inserm, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France.
Nucleic Acids Res. 2025 May 10;53(9). doi: 10.1093/nar/gkaf434.
The hijacking of CRM1 export is an important step of the retroviral replication cycle. Here, we investigated the consequences of this hijacking for the host. During HTLV-1 infection, we identified that this hijacking by the viral protein Rex favours the association between CRM1 and the RNA helicase UPF1, leading to a decreased affinity of UPF1 for cellular RNA and its nuclear retention. As a consequence, we found that the nonsense-mediated mRNA decay (NMD), known to have an antiviral function, was inhibited. Corroborating these results, we described a similar process with Rev, the functional homolog of Rex from HIV-1. Unexpectedly, we also found that, for HTLV-1, this process is coupled with the specific loading of UPF1 onto vRNA, independently of NMD. In this latter context, UPF1 positively regulates several steps of the viral replication cycle, from the nuclear export of vRNA to the production of mature viral particles.
CRM1 输出的劫持是逆转录病毒复制周期的重要步骤。在此，我们研究了这种劫持对宿主的影响。在 HTLV-1 感染期间，我们发现病毒蛋白 Rex 的这种劫持有利于 CRM1 与 RNA 解旋酶 UPF1 之间的结合，导致 UPF1 对细胞 RNA 的亲和力降低及其在细胞核内的滞留。因此，我们发现已知具有抗病毒功能的无义介导的 mRNA 衰变（NMD）受到抑制。为证实这些结果，我们描述了与 HIV-1 的 Rex 功能同源物 Rev 的类似过程。出乎意料的是，我们还发现，对于 HTLV-1，这一过程与 UPF1 独立于 NMD 特异性加载到病毒 RNA（vRNA）上有关。在后一种情况下，UPF1 正向调节病毒复制周期的几个步骤，从 vRNA 的核输出到成熟病毒颗粒的产生。
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