title: Spread of infection and lymphocyte depletion in mice depends on polymerase of influenza virus.
abstract: SC35M is a mouse-adapted variant of the highly pathogenic avian influenza virus SC35. We have previously shown that interspecies adaptation is mediated by mutations in the viral polymerase and that it is paralleled by the acquisition of high pathogenicity for mice. In the present study, we have compared virus spread and organ tropism of SC35 and SC35M in mice. We show that SC35 virus causes mild bronchiolitis in these animals, whereas infection with the mouse-adapted SC35M virus leads to severe hemorrhagic pneumonia with dissemination to other organs, including the brain. In SC35M-infected animals, viral RNA and viral antigen were detected in monocytes and macrophages, and SC35M, unlike SC35, replicated in lymphocyte and macrophage cultures in vitro. SC35M did not induce an adequate cytokine response but, unlike SC35, caused severe lymphopenia in mice. These observations suggest that the high efficiency of the SC35M polymerase is responsible for infection and depletion of lymphocytes and other white blood cells, which results in immune suppression and systemic virus spread.
authors.affiliation: Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, an der Universität Hamburg, Martinistrasse 52, Hamburg, Germany. guelsah.gabriel@hpi.uni-hamburg.de
authors.forename: Gülsah
authors.initials: G
authors.lastname: Gabriel
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
authors.forename: Oliver
authors.initials: O
authors.lastname: Planz
authors.forename: Katja
authors.initials: K
authors.lastname: Bier
authors.forename: Astrid
authors.initials: A
authors.lastname: Herwig
authors.forename: Martina
authors.initials: M
authors.lastname: Sauter
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Klenk
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001988:Bronchiolitis / Q000209:etiology / Q000503:physiopathology; D002478:Cells, Cultured; D002642:Chick Embryo; D007165:Immunosuppression Therapy; D053126:Influenza A Virus, H7N7 Subtype / Q000235:genetics / Q000472:pathogenicity; D009980:Influenza A virus / Q000235:genetics / Q000472:pathogenicity*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology*; D011024:Pneumonia, Viral / Q000209:etiology / Q000503:physiopathology; D012367:RNA, Viral / Q000032:analysis
chemical_list: D000956:Antigens, Viral; D012367:RNA, Viral
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