Rajaiah Rajesh, Pandey Kabita, Acharya Arpan, Ambikan Anoop, Kumar Narendra, Guda Reema, Avedissian Sean N, Montaner Luis J, Cohen Samuel M, Neogi Ujjwal, Byrareddy Siddappa N
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
The Systems Virology Lab, Department of Laboratory Medicine, Division of Clinical Microbiology, ANA Futura, Karolinska Institutet, 141 52 Stockholm, Sweden.
iScience. 2024 Jul 14;27(8):110501. doi: 10.1016/j.isci.2024.110501. eCollection 2024 Aug 16.
Delta (B.1.617.2) and Omicron (B.1.1.529) variants of SARS-CoV-2 represents unique clinical characteristics. However, their role in altering immunometabolic regulations during acute infection remains convoluted. Here, we evaluated the differential immunopathogenesis of Delta vs. Omicron variants in Golden Syrian hamsters (GSH). The Delta variant resulted in higher virus titers in throat swabs and the lungs and exhibited higher lung damage with immune cell infiltration than the Omicron variant. The gene expression levels of immune mediators and metabolic enzymes, Arg-1 and IDO1 in the Delta-infected lungs were significantly higher compared to Omicron. Further, Delta/Omicron infection perturbed carbohydrates, amino acids, nucleotides, and TCA cycle metabolites and was differentially regulated compared to uninfected lungs. Collectively, our data provide a novel insight into immunometabolic/pathogenic outcomes for Delta vs. Omicron infection in the GSH displaying concordance with COVID-19 patients associated with inflammation and tissue injury during acute infection that offered possible new targets to develop potential therapeutics.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的德尔塔（B.1.617.2）和奥密克戎（B.1.1.529）变体具有独特的临床特征。然而，它们在急性感染期间改变免疫代谢调节方面的作用仍然错综复杂。在此，我们评估了叙利亚金黄地鼠（GSH）中德尔塔变体与奥密克戎变体的不同免疫发病机制。与奥密克戎变体相比，德尔塔变体在咽喉拭子和肺部产生了更高的病毒滴度，并且表现出更高的肺部损伤以及免疫细胞浸润。与奥密克戎感染的肺部相比，德尔塔感染的肺部中免疫介质和代谢酶、精氨酸酶1（Arg-1）和吲哚胺2,3-双加氧酶1（IDO1）的基因表达水平显著更高。此外，德尔塔/奥密克戎感染扰乱了碳水化合物、氨基酸、核苷酸和三羧酸循环代谢物，并且与未感染的肺部相比受到不同的调节。总体而言，我们的数据为GSH中德尔塔与奥密克戎感染的免疫代谢/致病结果提供了新的见解，与急性感染期间伴有炎症和组织损伤的新冠肺炎患者情况一致，这为开发潜在治疗方法提供了可能的新靶点。
