title: Replication in cells of hematopoietic origin is necessary for Dengue virus dissemination.
abstract: Dengue virus (DENV) is a mosquito-borne pathogen for which no vaccine or specific therapeutic is available. Although it is well established that dendritic cells and macrophages are primary sites of DENV replication, it remains unclear whether non-hematopoietic cellular compartments serve as virus reservoirs. Here, we exploited hematopoietic-specific microRNA-142 (miR-142) to control virus tropism by inserting tandem target sites into the virus to restrict replication exclusively in this cell population. In vivo use of this virus restricted infection of CD11b+, CD11c+, and CD45+ cells, resulting in a loss of virus spread, regardless of the route of administration. Furthermore, sequencing of the targeted virus population that persisted at low levels, demonstrated total excision of the inserted miR-142 target sites. The complete conversion of the virus population under these selective conditions suggests that these immune cells are the predominant sources of virus amplification. Taken together, this work highlights the importance of hematopoietic cells for DENV replication and showcases an invaluable tool for the study of virus pathogenesis.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Alissa M
authors.initials: AM
authors.lastname: Pham
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Langlois
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: TenOever
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003715:Dengue / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003716:Dengue Virus / Q000502:physiology*; D057809:HEK293 Cells; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
chemical_list: D015703:Antigens, CD; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse