title: Experimental infection of suckling mice by subcutaneous inoculation with Oropouche virus.
abstract: Oropouche virus, of the family Bunyaviridae, genus Orthobunyavirus, serogroup Simbu, is an important causative agent of arboviral febrile illness in Brazil. An estimated 500,000 cases of Oropouche fever have occurred in Brazil in the last 30 years, with recorded cases also in Panama, Peru, Suriname and Trinidad. We have developed an experimental model of Oropouche virus infection in neonatal BALB/c mouse by subcutaneous inoculation. The vast majority of infected animals developed disease on the 5th day post infection, characterized mainly by lethargy and paralysis, progressing to death within 10 days. Viral replication was documented in brain cells by in situ hybridization, immunohistochemistry and virus titration. Multi-step immunohistochemistry indicated neurons as the main target cells of OROV infection. Histopathology revealed glial reaction and astrocyte activation in the brain and spinal cord, with neuronal apoptosis. Spleen hyperplasia and mild meningitis were also found, without viable virus detected in liver and spleen. This is the first report of an experimental mouse model of OROV infection, with severe involvement of the central nervous system, and should become useful in pathogenesis studies, as well as in preclinical testing of therapeutic interventions for this emerging pathogen.
authors.affiliation: Department of Cell Biology, University of São Paulo School of Medicine, Ribeirão Preto, Brazil. risantos@usp.br
authors.forename: Rodrigo I
authors.initials: RI
authors.lastname: Santos
authors.forename: Mariana F P
authors.initials: MF
authors.lastname: Almeida
authors.forename: Flávia E
authors.initials: FE
authors.lastname: Paula
authors.forename: Alcir Humberto
authors.initials: AH
authors.lastname: Rodrigues
authors.forename: Ariane Mattioli
authors.initials: AM
authors.lastname: Saranzo
authors.forename: André E
authors.initials: AE
authors.lastname: Paula
authors.forename: Maria Lúcia
authors.initials: ML
authors.lastname: Silva
authors.forename: Vani Maria Alves
authors.initials: VM
authors.lastname: Correa
authors.forename: Gustavo Olszanski
authors.initials: GO
authors.lastname: Acrani
authors.forename: Luciano
authors.initials: L
authors.lastname: Neder
authors.forename: Eurico
authors.initials: E
authors.lastname: Arruda
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology / Q000821:virology; D002044:Bunyaviridae Infections / Q000401:mortality / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000473:pathology; D012840:Simbu virus / Q000472:pathogenicity*; D013116:Spinal Cord / Q000473:pathology / Q000821:virology; D019562:Viral Load; D015431:Weight Loss