Understanding SARS-CoV-2 immune pathology is critical for the development of effective vaccines and treatments. Here, we employed unbiased serial whole-blood transcriptome profiling by weighted gene network correlation analysis (WGCNA) at pre-specified timepoints of infection to understand SARS-CoV-2-related immune alterations in a cohort of rhesus macaques (RMs) and African green monkeys (AGMs) presenting with varying degrees of pulmonary pathology. We found that the bulk of transcriptional changes occurred at day 3 post-infection and normalized to pre-infection levels by 3 weeks. There was evidence of coordination of transcriptional networks in blood (defined by WGCNA) and the nasopharyngeal SARS-CoV-2 burden as well as the absolute monocyte count. Pathway analysis of gene modules revealed prominent regulation of type I and type II interferon stimulated genes (ISGs) in both RMs and AGMs, with the latter species exhibiting a greater breadth of ISG upregulation. Notably, pathways relating to neutrophil degranulation were enriched in blood of SARS-CoV-2 infected AGMs, but not RMs. Our results elude to hallmark similarities as well as differences in the RM and AGM acute response to SARS-CoV-2 infection, and may help guide the selection of particular NHP species in modeling aspects of COVID-19 disease outcome.
【저자키워드】 COVID-19, interferon, Systems biology, African green monkey, neutrophil (PMN), 【초록키워드】 Transcriptome, SARS-CoV-2, pathology, SARS-COV-2 infection, Infection, outcome, immune, COVID-19 disease, Cohort, nasopharyngeal, pathway, understanding, Critical, WGCNA, ISGs, Blood, breadth, ISG, rhesus macaque, Evidence, Analysis, gene network, similarity, Pulmonary pathology, Post-infection, Correlation analysis, Regulation, type I, alteration, help, upregulation, neutrophil degranulation, hallmark, acute response, NHP, AGMs, transcriptional, stimulated, greater, defined, occurred, effective vaccine, presenting, exhibiting, transcriptional change, absolute monocyte count, AGM, normalized, timepoint, 【제목키워드】 SARS-CoV-2, response, African, macaque, Monkey, green, difference,