title: Switch to high-level virus replication and HLA class I upregulation in differentiating megakaryocytic cells after infection with pathogenic hantavirus.
abstract: Hantaan virus (HTNV), the prototype member of the Hantavirus genus in the family Bunyaviridae, causes hemorrhagic fever with renal syndrome (HFRS) in humans. Hemorrhage is due to endothelial barrier damage and a sharp decrease in platelet counts. The mechanisms underlying HTNV-associated acute thrombocytopenia have not been elucidated so far. Platelets are produced by mature megakaryocytes that develop during megakaryopoiesis. In this study, we show that HTNV targets megakaryocytic cells whereas rather non-pathogenic hantaviruses did not infect this cell type. After induction of differentiation megakaryocytic cells switched from low-level to high-level HTNV production without reduction in cell survival or alteration in differentiation. However, increased HTNV replication resulted in strong upregulation of HLA class I molecules although HTNV escaped type I interferon (IFN)-associated innate responses. Taken together, HTNV efficiently replicates in differentiating megakaryocytic cells resulting in upregulation of HLA class I molecules, the target structures for cytotoxic T cells (CTLs).
authors.affiliation: Institute of Medical Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Lütteke
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Raftery
authors.forename: Pritesh
authors.initials: P
authors.lastname: Lalwani
authors.forename: Min-Hi
authors.initials: MH
authors.lastname: Lee
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.forename: Sebastian
authors.initials: S
authors.lastname: Voigt
authors.forename: Norbert
authors.initials: N
authors.lastname: Bannert
authors.forename: Harald
authors.initials: H
authors.lastname: Schulze
authors.forename: Detlev H
authors.initials: DH
authors.lastname: Krüger
authors.forename: Günther
authors.initials: G
authors.lastname: Schönrich
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D005805:Genes, MHC Class I / Q000235:genetics / Q000502:physiology*; D018063:Hantaan virus / Q000472:pathogenicity*; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology* / Q000821:virology*; D015854:Up-Regulation; D014709:Vero Cells; D014779:Virus Replication / Q000502:physiology*