Yadav Santosh K, Gawargi Flobater I, Hasan Mohammad H, Tandon Ritesh, Upton Jason W, Mishra Paras K
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Cell and Molecular Biology, Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS, USA.
Cell Death Discov. 2023 Apr 3;9(1):111. doi: 10.1038/s41420-023-01408-y.
Cytomegalovirus (CMV) is a widely prevalent herpesvirus that reaches seroprevalence rates of up to 95% in several parts of the world. The majority of CMV infections are asymptomatic, albeit they have severe detrimental effects on immunocompromised individuals. Congenital CMV infection is a leading cause of developmental abnormalities in the USA. CMV infection is a significant risk factor for cardiovascular diseases in individuals of all ages. Like other herpesviruses, CMV regulates cell death for its replication and establishes and maintains a latent state in the host. Although CMV-mediated regulation of cell death is reported by several groups, it is unknown how CMV infection affects necroptosis and apoptosis in cardiac cells. Here, we infected primary cardiomyocytes, the contractile cells in the heart, and primary cardiac fibroblasts with wild-type and cell-death suppressor deficient mutant CMVs to determine how CMV regulates necroptosis and apoptosis in cardiac cells. Our results reveal that CMV infection prevents TNF-induced necroptosis in cardiomyocytes; however, the opposite phenotype is observed in cardiac fibroblasts. CMV infection also suppresses inflammation, reactive oxygen species (ROS) generation, and apoptosis in cardiomyocytes. Furthermore, CMV infection improves mitochondrial biogenesis and viability in cardiomyocytes. We conclude that CMV infection differentially affects the viability of cardiac cells.
巨细胞病毒(CMV)是一种广泛流行的疱疹病毒,在世界上多个地区血清阳性率高达95%。大多数CMV感染是无症状的,尽管它们对免疫功能低下的个体有严重的有害影响。先天性CMV感染是美国发育异常的主要原因。CMV感染是所有年龄段个体患心血管疾病的重要危险因素。与其他疱疹病毒一样,CMV为了自身复制而调节细胞死亡,并在宿主中建立和维持潜伏状态。尽管有几个研究小组报道了CMV介导的细胞死亡调节,但CMV感染如何影响心脏细胞中的坏死性凋亡和凋亡尚不清楚。在这里,我们用野生型和细胞死亡抑制缺陷型突变CMV感染原代心肌细胞(心脏中的收缩细胞)和原代心脏成纤维细胞,以确定CMV如何调节心脏细胞中的坏死性凋亡和凋亡。我们的结果表明,CMV感染可防止TNF诱导的心肌细胞坏死性凋亡;然而,在心脏成纤维细胞中观察到相反的表型。CMV感染还可抑制心肌细胞中的炎症、活性氧(ROS)生成和凋亡。此外,CMV感染可改善心肌细胞中的线粒体生物合成和活力。我们得出结论,CMV感染对心脏细胞的活力有不同的影响。