PMID- 25678530 OWN - NLM STAT- MEDLINE DCOM- 20150821 LR - 20221207 IS - 1465-2099 (Electronic) IS - 0022-1317 (Linking) VI - 96 IP - Pt 6 DP - 2015 Jun TI - Hantavirus-induced pathogenesis in mice with a humanized immune system. PG - 1258-1263 LID - 10.1099/vir.0.000087 [doi] AB - 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. CI - (c) 2015 The Authors. FAU - Kobak, Lidija AU - Kobak L AD - Institute of Medical Virology, Helmut-Ruska-Haus, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Raftery, Martin J AU - Raftery MJ AD - Institute of Medical Virology, Helmut-Ruska-Haus, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Voigt, Sebastian AU - Voigt S AD - Department of Pediatric Oncology and Hematology, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Division of Viral Infections, Robert Koch Institute, Berlin, Germany. FAU - Kuhl, Anja A AU - Kuhl AA AD - Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology/RCIS, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Kilic, Ergin AU - Kilic E AD - Institute of Pathology, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Kurth, Andreas AU - Kurth A AD - Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany. FAU - Witkowski, Peter AU - Witkowski P AD - Institute of Medical Virology, Helmut-Ruska-Haus, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Hofmann, Jorg AU - Hofmann J AD - Division of Virology, Labor Berlin Charite-Vivantes GmbH, Berlin, Germany. AD - Institute of Medical Virology, Helmut-Ruska-Haus, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Nitsche, Andreas AU - Nitsche A AD - Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany. FAU - Schaade, Lars AU - Schaade L AD - Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany. FAU - Kruger, Detlev H AU - Kruger DH AD - Institute of Medical Virology, Helmut-Ruska-Haus, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Schonrich, Gunther AU - Schonrich G AD - Institute of Medical Virology, Helmut-Ruska-Haus, Charite-Universitatsmedizin Berlin, Berlin, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150212 PL - England TA - J Gen Virol JT - The Journal of general virology JID - 0077340 SB - IM MH - Animals MH - Body Weight MH - *Disease Models, Animal MH - Orthohantavirus/growth & development/pathogenicity/*physiology MH - Hantavirus Infections/*pathology/*virology MH - *Host-Pathogen Interactions MH - Humans MH - Mice, SCID MH - Platelet Count EDAT- 2015/02/14 06:00 MHDA- 2015/08/22 06:00 CRDT- 2015/02/14 06:00 PHST- 2014/11/07 00:00 [received] PHST- 2015/02/04 00:00 [accepted] PHST- 2015/02/14 06:00 [entrez] PHST- 2015/02/14 06:00 [pubmed] PHST- 2015/08/22 06:00 [medline] AID - 10.1099/vir.0.000087 [doi] PST - ppublish SO - J Gen Virol. 2015 Jun;96(Pt 6):1258-1263. doi: 10.1099/vir.0.000087. Epub 2015 Feb 12.