title: Single-cell tracking of flavivirus RNA uncovers species-specific interactions with the immune system dictating disease outcome.
abstract: Positive-sense RNA viruses pose increasing health and economic concerns worldwide. Our limited understanding of how these viruses interact with their host and how these processes lead to virulence and disease seriously hampers the development of anti-viral strategies. Here, we demonstrate the tracking of (+) and (-) sense viral RNA at single-cell resolution within complex subsets of the human and murine immune system in different mouse models. Our results provide insights into how a prototypic flavivirus, yellow fever virus (YFV-17D), differentially interacts with murine and human hematopoietic cells in these mouse models and how these dynamics influence distinct outcomes of infection. We detect (-) YFV-17D RNA in specific secondary lymphoid compartments and cell subsets not previously recognized as permissive for YFV replication, and we highlight potential virus-host interaction events that could be pivotal in regulating flavivirus virulence and attenuation.
authors.affiliation: Department of Molecular Biology, Princeton University, 110 Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Douam
authors.affiliation: Department of Molecular Biology, Princeton University, 110 Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hrebikova
authors.affiliation: Department of Molecular Biology, Princeton University, 110 Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA.
authors.forename: Yentli E Soto
authors.initials: YE
authors.lastname: Albrecht
authors.affiliation: Department of Molecular Biology, Princeton University, 110 Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Sellau
authors.affiliation: Department of Molecular Biology, Princeton University, 110 Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA.
authors.forename: Yael
authors.initials: Y
authors.lastname: Sharon
authors.affiliation: Department of Molecular Biology, Princeton University, 110 Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Molecular Biology, Princeton University, 110 Lewis Thomas Laboratory, Washington Road, Princeton, New Jersey 08544, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploss
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D005416:Flavivirus / Q000235:genetics; D005434:Flow Cytometry; D057809:HEK293 Cells; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism*; D059010:Single-Cell Analysis; D013045:Species Specificity; D014183:Transplantation, Heterologous; D015004:Yellow Fever / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D015005:Yellow fever virus / Q000235:genetics*
chemical_list: D016207:Cytokines; D012367:RNA, Viral