![]() Experiments involving live EBOV require maximum containment (e.g., biosafety level 4 ) and therefore are restricted to a small number of highly specialized research facilities. Studies of EVD pathogenesis, while paramount, face numerous logistical challenges which have limited their scope relative to studies of other pathogens. While recently developed vaccines ( Kennedy et al., 2017) and monoclonal antibody therapeutics ( Mulangu et al., 2019) have shown great promise for preventing and treating EVD, case fatality rates in treated patients still exceed 30%, highlighting the need for further research into disease pathogenesis. EBOV infection in humans causes Ebola virus disease (EVD), characterized by fever, malaise, muscle aches, and gastrointestinal distress, rapidly progressing to coagulopathy, shock, and multi-organ failure ( Malvy et al., 2019). Overall, this study sheds light on EBOV tropism, replication dynamics, and elicited immune response, and provides a framework for characterizing interactions between hosts and emerging viruses in a maximum containment setting.Įbola virus (EBOV) is among the world’s most lethal pathogens, with an estimated case fatality rate of 66% in the recent epidemic in the Democratic Republic of the Congo ( Ilunga Kalenga et al., 2019 World Health Organization, 2019) and 40% in the 2013–2016 epidemic in West Africa ( Lo et al., 2017). Within infected cells, we observe that EBOV down-regulates STAT1 mRNA and interferon signaling, and up-regulates putative pro-viral genes (e.g., DYNLL1 and HSPA5), nominating cellular pathways the virus manipulates for its replication. By quantifying viral RNA abundance in individual cells, we identify molecular determinants of tropism and examine temporal dynamics in viral and host gene expression. We find that immature, proliferative monocyte-lineage cells with reduced antigen presentation capacity replace conventional circulating monocyte subsets within days of infection, while lymphocytes upregulate apoptosis genes and decline in abundance. ![]() We obtained 100,000 transcriptomes and 15,000,000 protein profiles, providing insight into pathogenesis. ![]() ![]() To better understand EBOV infection in vivo, we used single-cell transcriptomics and CyTOF-based single-cell protein quantification to characterize peripheral immune cell activity during EBOV infection in rhesus monkeys. Ebola virus (EBOV) causes epidemics with high case fatality rates, yet remains understudied due to the challenge of experimentation in high-containment and outbreak settings. ![]()
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