Callon Domitille, Lebreil Anne-Laure, Bouland Nicole, Fichel Caroline, Fornès Paul, Andreoletti Laurent, Berri Fatma
Cardiovir EA-4684, UFR Médecine, Université de Reims Champagne-Ardenne, 51100 Reims, France.
Pathology Department, CHU Reims, Hôpital Robert Debré, 51100 Reims, France.
Vaccines (Basel). 2022 Jul 28;10(8):1203. doi: 10.3390/vaccines10081203.
Major EV-B populations characterized by 5′ terminal deletions (5′TD) have been shown to be associated with the development of myocarditis and type 1 diabetes in mice or humans. To date, the dynamics of EV-B 5′TD-RNA forms’ emergence during the course of infection and their impact on cellular functions remain unclear. Using a RACE-PCR approach in CVB3/28-infected mouse organs, we showed an early (3 days post infection, DPI) emergence of major 5′TD populations associated with minor full-length RNA forms. Viral replication activities with infectious particle production were associated with heart, liver, and pancreas acute inflammatory lesions, whereas clearance of viral RNA without organ lesions was observed in the brain, lung, intestines, and muscles from 3 to 7 DPI. At 28 DPI, low viral RNA levels, +/-RNA ratios < 5 associated with viral protein 1 expression revealed a persistent infection in the heart and pancreas. This persistent infection was characterized by molecular detection of only 5′TD RNA forms that were associated with dystrophin cleavage in the heart and insulin production impairment in beta-pancreatic cells. These results demonstrated that major EV-B 5′TD RNA forms can be early selected during systemic infection and that their maintenance may drive EV-induced acute and persistent infections with target cell dysfunctions.
以5′末端缺失（5′TD）为特征的主要肠道病毒B群已被证明与小鼠或人类的心肌炎和1型糖尿病的发生有关。迄今为止，肠道病毒B群5′TD-RNA形式在感染过程中出现的动态变化及其对细胞功能的影响仍不清楚。通过在感染柯萨奇病毒B3/28的小鼠器官中使用RACE-PCR方法，我们发现主要的5′TD群体在早期（感染后3天，dpi）出现，同时伴有少量全长RNA形式。具有感染性颗粒产生的病毒复制活动与心脏、肝脏和胰腺的急性炎性病变有关，而在3至7 dpi时，在脑、肺、肠和肌肉中观察到无器官病变的病毒RNA清除。在28 dpi时，低病毒RNA水平、+/-RNA比率<5且与病毒蛋白1表达相关，表明心脏和胰腺存在持续感染。这种持续感染的特征是仅分子检测到与心脏中肌营养不良蛋白裂解和β胰腺细胞中胰岛素产生受损相关的5′TD RNA形式。这些结果表明，主要的肠道病毒B群5′TD RNA形式可在全身感染期间早期被选择，并且它们的维持可能导致肠道病毒诱导的急性和持续感染以及靶细胞功能障碍。
