title: Early and late pathogenic events of newborn mice encephalitis experimentally induced by itacaiunas and curionópolis bracorhabdoviruses infection.
abstract: In previous reports we proposed a new genus for Rhabdoviridae and described neurotropic preference and gross neuropathology in newborn albino Swiss mice after Curionopolis and Itacaiunas infections. In the present report a time-course study of experimental encephalitis induced by Itacaiunas and Curionopolis virus was conducted both in vivo and in vitro to investigate cellular targets and the sequence of neuroinvasion. We also investigate, after intranasal inoculation, clinical signs, histopathology and apoptosis in correlation with viral immunolabeling at different time points. Curionopolis and Itacaiunas viral antigens were first detected in the parenchyma of olfactory pathways at 2 and 3 days post-inoculation (dpi) and the first clinical signs were observed at 4 and 8 dpi, respectively. After Curionopolis infection, the mortality rate was 100% between 5 and 6 dpi, and 35% between 8 and 15 dpi after Itacaiunas infection. We identified CNS mice cell types both in vivo and in vitro and the temporal sequence of neuroanatomical olfactory areas infected by Itacaiunas and Curionopolis virus. Distinct virulences were reflected in the neuropathological changes including TUNEL immunolabeling and cytopathic effects, more intense and precocious after intracerebral or in vitro inoculations of Curionopolis than after Itacaiunas virus. In vitro studies revealed neuronal but not astrocyte or microglial cytopathic effects at 2 dpi, with monolayer destruction occurring at 5 and 7 dpi with Curionopolis and Itacaiunas virus, respectively. Ultrastructural changes included virus budding associated with interstitial and perivascular edema, endothelial hypertrophy, a reduced and/or collapsed small vessel luminal area, thickening of the capillary basement membrane, and presence of phagocytosed apoptotic bodies. Glial cells with viral budding similar to oligodendrocytes were infected with Itacaiunas virus but not with Curionopolis virus. Thus, Curionopolis and Itacaiunas viruses share many pathological and clinical features present in other rhabdoviruses but distinct virulence and glial targets in newborn albino Swiss mice brain.
authors.affiliation: Instituto Evandro Chagas, Belém, Brazil.
authors.forename: José Antonio Picanço
authors.initials: JA
authors.lastname: Diniz
authors.forename: Zaire Alves
authors.initials: ZA
authors.lastname: Dos Santos
authors.forename: Marcio Augusto Galvão
authors.initials: MA
authors.lastname: Braga
authors.forename: Adila Liliane Barros
authors.initials: AL
authors.lastname: Dias
authors.forename: Daisy Elaine Andrade
authors.initials: DE
authors.lastname: da Silva
authors.forename: Daniele Barbosa
authors.initials: DB
authors.lastname: de Almeida Medeiros
authors.forename: Vera Lucia Reis
authors.initials: VL
authors.lastname: de Souza Barros
authors.forename: Jannifer Oliveira
authors.initials: JO
authors.lastname: Chiang
authors.forename: Kendra Eyllen
authors.initials: KE
authors.lastname: de Freitas Zoghbi
authors.forename: Juarez Antônio Simões
authors.initials: JA
authors.lastname: Quaresma
authors.forename: Christina Maeda
authors.initials: CM
authors.lastname: Takiya
authors.forename: Vivaldo
authors.initials: V
authors.lastname: Moura Neto
authors.forename: Wanderley
authors.initials: W
authors.lastname: de Souza
authors.forename: Pedro Fernando
authors.initials: PF
authors.lastname: da Costa Vasconcelos
authors.forename: Cristovam Wanderley Picanço
authors.initials: CW
authors.lastname: Diniz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001921:Brain / Q000196:embryology / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000209:etiology / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D007124:Immunoenzyme Techniques; D051379:Mice; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000821:virology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000821:virology; D011247:Pregnancy; D012209:Rhabdoviridae / Q000145:classification* / Q000472:pathogenicity*; D018353:Rhabdoviridae Infections / Q000473:pathology* / Q000821:virology