title: Infectivity of rabies virus-exposed macrophages.
abstract: Rabies virus distributes widely in infected mice, including lymphoid tissues and spleen macrophages. The infection characteristics in murine macrophages and the infectivity of virus-exposed macrophages were examined upon inoculation in mice. In vitro, Mf4/4 spleen macrophages supported mild virus production (10(4)-fold less than neuroblastoma), with formation of typical virions. Bone marrow-derived macrophages (BMM) were most efficient to capture virus, but new virus production was not detected. Virus-induced cell death was significantly stronger in BMM, which might have eliminated BMM with productive infection. Still, viral RNA remained detectable in the remaining BMM for at least 4 weeks. Injection of in vitro-infected Mf4/4 in the nose or brain proved efficient to propagate infection in mice, even when cells were pre-incubated with neutralizing antibodies. Surprisingly, injection of ex-vivo-infected BMM in the brain also led to lethal infection in 8 out of 12 mice. Injection of infected Mf4/4 in the muscle mostly favoured a protective antibody response. Despite that macrophages are less fit to support virus production, they can still act as a source of infectious virus upon transfer in mice. This may be relevant for screening donor organs/cells, for which RT-PCR should be preferred over the traditional antigen or virus isolation assays.
authors.affiliation: National Reference Laboratory of Rabies, Viral Diseases, Communicable and Infectious Diseases, Scientific Institute of Public Health, Engeland St. 642, B-1180 Brussels, Belgium.
authors.forename: Florence
authors.initials: F
authors.lastname: Nazé
authors.forename: Vanessa
authors.initials: V
authors.lastname: Suin
authors.forename: Sophie
authors.initials: S
authors.lastname: Lamoral
authors.forename: Aurélie
authors.initials: A
authors.lastname: Francart
authors.forename: Bernard
authors.initials: B
authors.lastname: Brochier
authors.forename: Stefan
authors.initials: S
authors.lastname: Roels
authors.forename: Jan
authors.initials: J
authors.lastname: Mast
authors.forename: Michael
authors.initials: M
authors.lastname: Kalai
authors.forename: Steven
authors.initials: S
authors.lastname: Van Gucht
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation; D000956:Antigens, Viral / Q000032:analysis; D001853:Bone Marrow / Q000378:metabolism; D001921:Brain / Q000276:immunology / Q000473:pathology / Q000821:virology; D016923:Cell Death; D056724:Immunity, Humoral; D007273:Injections, Intramuscular; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009666:Nose / Q000473:pathology / Q000821:virology; D012367:RNA, Viral / Q000276:immunology*; D011818:Rabies / Q000276:immunology / Q000473:pathology / Q000821:virology; D011820:Rabies virus / Q000276:immunology / Q000472:pathogenicity* / Q000648:ultrastructure; D013154:Spleen / Q000166:cytology; D019562:Viral Load; D014776:Virus Cultivation / Q000379:methods
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D012367:RNA, Viral