Ghosh A, Alladi P A, Narayanappa G, Vasanthapuram R, Desai A
Acta Virol. 2018;62(4):360-373. doi: 10.4149/av_2018_403.
Chikungunya virus (CHIKV), a re-emerging Alphavirus, causes chronic myalgia and arthralgia in infected individuals. However, the exact pathophysiology remains undefined till date. Virus induced time course changes in host cells at the ultrastructural level and host cytoskeleton have been reported for other alphaviruses such as Sindbis and Semliki Forest virus. Few studies have tried to delineate the same for CHIKV leading to some understanding of the replication process. Selective CHIKV infection of progenitor cells involved in muscle repair has been proposed as a cause of myalgia; albeit the outcome of infection on these cells has not been reported. With this background, we investigated CHIKV-induced time course changes in two cell lines - Aedes albopictus (C6/36) and murine myoblasts (C2C12) by transmission electron microscopy (TEM). CHIKV infection of C2C12 cells resulted in cell death, with cells exhibiting well defined apoptotic features. In contrast, mature virions were released from infected C6/36 cells without cytolysis. Double labelling of C2C12 cytoskeletal proteins - such as actin, tubulin and CHIKV revealed that viral nucleocapsids co-localized with these proteins during replication. As the infection progressed, CHIKV disrupted the normal organisation of these cell proteins. CHIKV-induced plasma membrane extensions were observed in infected cells, which so far have been reported only for Sindbis virus. This is a first report describing the time course of morphological changes occurring in host cells as a result of infection with CHIKV at the ultrastructural level. Apoptosis of myoblasts due to CHIKV infection could also be an important factor contributing to the recurrence of myalgia in CHIKV patients. Keywords: Chikungunya; electron microscopy; confocal microscopy; C6/36; C2C12; actin; α-tubulin.
基孔肯雅病毒（CHIKV）是一种再度出现的甲病毒，可导致感染者出现慢性肌痛和关节痛。然而，确切的病理生理学至今仍不明确。对于辛德比斯病毒和塞米基森林病毒等其他甲病毒，已有关于病毒诱导宿主细胞在超微结构水平和宿主细胞骨架上的时间进程变化的报道。很少有研究试图描绘基孔肯雅病毒的相同情况，从而对其复制过程有了一些了解。有人提出，参与肌肉修复的祖细胞受到基孔肯雅病毒的选择性感染是肌痛的一个原因；尽管尚未报道这些细胞的感染结果。在此背景下，我们通过透射电子显微镜（TEM）研究了基孔肯雅病毒在两种细胞系——白纹伊蚊（C6/36）和小鼠成肌细胞（C2C12）中诱导的时间进程变化。基孔肯雅病毒感染C2C12细胞导致细胞死亡，细胞表现出明确的凋亡特征。相比之下，成熟病毒粒子从感染的C6/36细胞中释放出来，没有细胞溶解现象。对C2C12细胞骨架蛋白（如肌动蛋白、微管蛋白和基孔肯雅病毒）进行双重标记显示，病毒核衣壳在复制过程中与这些蛋白共定位。随着感染的进展，基孔肯雅病毒破坏了这些细胞蛋白的正常组织。在感染细胞中观察到基孔肯雅病毒诱导的质膜延伸，迄今为止，这仅在辛德比斯病毒中报道过。这是第一份描述宿主细胞因感染基孔肯雅病毒而在超微结构水平上发生形态变化的时间进程的报告。基孔肯雅病毒感染导致成肌细胞凋亡也可能是基孔肯雅病毒患者肌痛复发的一个重要因素。关键词：基孔肯雅热；电子显微镜；共聚焦显微镜；C6/36；C2C12；肌动蛋白；α-微管蛋白。
