title: Hantavirus-induced pathogenesis in mice with a humanized immune system.
abstract: Hantaviruses are emerging zoonotic pathogens that can cause severe disease in humans. Clinical observations suggest that human immune components contribute to hantavirus-induced pathology. To address this issue we generated mice with a humanized immune system. Hantavirus infection of these animals resulted in systemic infection associated with weight loss, decreased activity, ruffled fur and inflammatory infiltrates of lung tissue. Intriguingly, after infection, humanized mice harbouring human leukocyte antigen (HLA) class I-restricted human CD8+ T cells started to lose weight earlier (day 10) than HLA class I-negative humanized mice (day 15). Moreover, in these mice the number of human platelets dropped by 77 % whereas the number of murine platelets did not change, illustrating how differences between rodent and human haemato-lymphoid systems may contribute to disease development. To our knowledge this is the first description of a humanized mouse model of hantavirus infection, and our results indicate a role for human immune cells in hantaviral pathogenesis.
authors: Institute of Medical Virology, Helmut-Ruska-Haus, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Lidija
authors: L
authors: Kobak
authors: Institute of Medical Virology, Helmut-Ruska-Haus, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Martin J
authors: MJ
authors: Raftery
authors: Department of Pediatric Oncology and Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany.|Division of Viral Infections, Robert Koch Institute, Berlin, Germany.
authors: Sebastian
authors: S
authors: Voigt
authors: Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology/RCIS, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Anja A
authors: AA
authors: Kühl
authors: Institute of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Ergin
authors: E
authors: Kilic
authors: Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.
authors: Andreas
authors: A
authors: Kurth
authors: Institute of Medical Virology, Helmut-Ruska-Haus, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Peter
authors: P
authors: Witkowski
authors: Division of Virology, Labor Berlin Charité-Vivantes GmbH, Berlin, Germany.|Institute of Medical Virology, Helmut-Ruska-Haus, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Jörg
authors: J
authors: Hofmann
authors: Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.
authors: Andreas
authors: A
authors: Nitsche
authors: Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.
authors: Lars
authors: L
authors: Schaade
authors: Institute of Medical Virology, Helmut-Ruska-Haus, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Detlev H
authors: DH
authors: Krüger
authors: Institute of Medical Virology, Helmut-Ruska-Haus, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors: Günther
authors: G
authors: Schönrich
mesh_terms: D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D006476:Orthohantavirus / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D018778:Hantavirus Infections / Q000473:pathology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016513:Mice, SCID; D010976:Platelet Count