Kaur Sardarni Urvinder, Ambikan Anoop T, Acharya Arpan, Johnson Samuel D, Avedissian Sean N, Végvári Ákos, Neogi Ujjwal, Byrareddy Siddappa N
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
The Systems Virology Laboratory, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.
Brain Behav Immun. 2025 Jan;123:914-927. doi: 10.1016/j.bbi.2024.10.032. Epub 2024 Oct 29.
Despite significant effort, a clear understanding of host tissue-specific responses and their implications for immunopathogenicity against the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) variant infection has remained poorly defined. To shed light on the interaction between tissues and SARS-CoV-2 variants, we sought to characterize the complex relationship among acute multisystem manifestations, dysbiosis of the gut microbiota, and the resulting implications for SARS-CoV-2 variant-specific immunopathogenesis in the Golden Syrian Hamster (GSH) model using multi-omics approaches. Our investigation revealed the presence of increased SARS-CoV-2 genomic RNA in diverse tissues of delta-infected GSH compared to the omicron variant. Multi-omics analyses uncovered distinctive metabolic responses between the delta and omicron variants, with the former demonstrating dysregulation in synaptic transmission proteins associated with neurocognitive disorders. Additionally, delta-infected GSH exhibited an altered fecal microbiota composition, marked by increased inflammation-associated taxa and reduced commensal bacteria compared to the omicron variant. These findings underscore the SARS-CoV-2-mediated tissue insult, characterized by modified host metabolites, neurological protein dysregulation, and gut dysbiosis, highlighting the compromised gut-lung-brain axis during acute infection.
尽管付出了巨大努力，但对于宿主组织特异性反应及其对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株感染免疫致病性的影响仍缺乏清晰的认识。为了阐明组织与SARS-CoV-2变异株之间的相互作用，我们试图利用多组学方法，在金黄叙利亚仓鼠（GSH）模型中，描述急性多系统表现、肠道微生物群失调以及由此对SARS-CoV-2变异株特异性免疫发病机制的影响之间的复杂关系。我们的研究发现，与奥密克戎变异株相比，感染德尔塔变异株的GSH的多种组织中SARS-CoV-2基因组RNA有所增加。多组学分析揭示了德尔塔变异株和奥密克戎变异株之间独特的代谢反应，前者表现出与神经认知障碍相关的突触传递蛋白失调。此外，与奥密克戎变异株相比，感染德尔塔变异株的GSH粪便微生物群组成发生改变，其特征是与炎症相关的分类群增加，共生细菌减少。这些发现强调了SARS-CoV-2介导的组织损伤，其特征是宿主代谢物改变、神经蛋白失调和肠道生态失调，突出了急性感染期间肠道-肺-脑轴受损。
