Single-cell profiling of Ebola virus infection in vivo reveals viral and host transcriptional dynamics

Kotliar, D.; Lin, A. E.; Logue, J.; Hughes, T. K.; Khoury, N. M.; Raju, S. S.; Wadsworth, M. H.; Chen, H.; Kurtz, J. R.; Dighero-Kemp, B.; Bjornson, Z. B.; Mukherjee, N.; Sellers, B. A.; Tran, N.; Bauer, M. R.; Adams, G. C.; Adams, R.; Rinn, J. L.; Mele, M.; Nolan, G. P.; Barnes, K. G.; Hensley, L. E.; McIlwain, D. R.; Shalek, A. K.; Sabeti, P. C.; Bennett, R. S.

doi:10.1101/2020.06.12.148957

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bioRxiv · 10.1101/2020.06.12.148957

Single-cell profiling of Ebola virus infection in vivo reveals viral and host transcriptional dynamics

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Abstract

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. 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. We obtained 100,000 transcriptomes and 15,000,000 protein profiles, providing insight into pathogenesis. 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. By quantifying viral RNA abundance in individual cells, we identify molecular determinants of tropism and examine temporal dynamics in viral and host gene expression. 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. 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.

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Kotliar, D., Lin, A. E., Logue, J., Hughes, T. K., Khoury, N. M., Raju, S. S., Wadsworth, M. H., Chen, H., Kurtz, J. R., Dighero-Kemp, B., Bjornson, Z. B., Mukherjee, N., Sellers, B. A., Tran, N., Bauer, M. R., Adams, G. C., Adams, R., Rinn, J. L., Mele, M., Nolan, G. P., Barnes, K. G., Hensley, L. E., McIlwain, D. R., Shalek, A. K., Sabeti, P. C., Bennett, R. S.. 2020-06-13. Single-cell profiling of Ebola virus infection in vivo reveals viral and host transcriptional dynamics. https://doi.org/10.1101/2020.06.12.148957

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