Differential Transcriptomic Landscapes of SARS-CoV-2 Variants in Multiple Organs from Infected Rhesus Macaques

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the persistent coronavirus disease 2019 (COVID-19) pandemic, which has resulted in millions of deaths worldwide and brought an enormous public health and global economic burden. The recurring global wave of infections has been exacerbated by growing variants of SARS-CoV-2. In this study, the virological characteristics of SARS-CoV-2 and its variants of concern (VOC, including Alpha, Beta, and Delta) in vitro and differential transcriptomic landscapes in multiple organs (lung, right ventricle, blood, cerebral cortex, and cerebellum) from the infected rhesus macaques were elucidated. The original strain of SARS-CoV-2 caused a stronger innate immune response in the host cells, and VOC markedly increased levels of subgenomic RNA (sgRNA), such as N, Orf9b, Orf6, and Orf7ab, which are known as innate immune antagonists and the inhibitor of antiviral factors. Intriguingly, the original SARS-CoV-2 strain and Alpha strain induced larger alteration of RNA abundance in tissues of rhesus monkeys than Beta and Delta variants did. Moreover, an hyperinflammatory state and active immune response were shown in right ventricle by the up-regulation of inflammation- and immune-related RNAs. Furthermore, peripheral blood may mediate signaling transmission among tissues to coordinate the molecular changes in the infected individuals. Collectively, these data provide insights into the pathogenesis of SARS-CoV-2 and its VOC infection in the early stage.