Single-cell profiling of ebola virus disease in vivo reveals viral and host dynamics

Biology Biology
Cell Atlas Cell Atlas
Genomics Genomics
Immunology Immunology
Infectious Disease Infectious Disease
Alex K. Shalek Alex K. Shalek
Marc Wadsworth II Marc Wadsworth II
Nancy Tran Nancy Tran
Travis Hughes Travis Hughes

Kotliar et al.▾ Kotliar, D.*, Lin, A.E.*, Logue, J., Hughes, T.K., Khoury, N.M., Raju, S.S., Wadsworth II, 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., Schaffner, S.F., Nolan, G.P.#, Barnes, K.G.#, Hensley, L.E.#, McIlwain, D.#, Shalek, A.K.#, Sabeti, P.C.#, Bennett, R.S.#

Cell , Volume 183

November, 2020


Ebola virus (EBOV) causes epidemics with high mortality yet remains understudied due to the challenge of experimentation in high-containment and outbreak settings. Here, we used single-cell transcriptomics and CyTOF-based single-cell protein quantification to characterize peripheral immune cells during EBOV infection in rhesus monkeys. We obtained 100,000 transcriptomes and 15,000,000 protein profiles, finding that immature, proliferative monocyte-lineage cells with reduced antigen-presentation capacity replace conventional monocyte subsets, while lymphocytes upregulate apoptosis genes and decline in abundance. By quantifying intracellular viral RNA, we identify molecular determinants of tropism among circulating immune cells and examine temporal dynamics in viral and host gene expression. Within infected cells, EBOV downregulates STAT1 mRNA and interferon signaling, and it upregulates putative pro-viral genes (e.g., DYNLL1 and HSPA5), nominating pathways the virus manipulates for its replication. This study sheds light on EBOV tropism, replication dynamics, and elicited immune response and provides a framework for characterizing host-virus interactions under maximum containment.