Pathogenesis of Equid Alphaherpesvirus 1 Infection in the Central Nervous System of Mice

Autor(es)

Mesquita, Leonardo P. ^{[1, 2]} ; Costa, Rafael C. ^[1] ; Mesquita, Lais L. R. ^[1] ; Lara, Maria do Carmo C. S. H. ^[3] ; Villalobos, Eliana M. C. ^[3] ; Mori, Claudia M. C. ^[1] ; Mori, Enio ^[4] ; Howerth, Elizabeth W. ^[2] ; Maiorka, Paulo C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sao Paulo - Brazil

^[2] Univ Georgia, Athens, GA - USA

^[3] Biol Inst, Sao Paulo - Brazil

^[4] Pasteur Inst, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: VETERINARY PATHOLOGY; v. 58, n. 6, p. 1075-1085, NOV 2021.
• Citações Web of Science: 0

Resumo

Equid alphaherpesvirus 1 (EHV-1) causes myeloencephalopathy in horses and occasionally in non-equid species. Although mouse models have been developed to understand EHV-1 pathogenesis, few EHV-1 strains have been identified as highly neurovirulent to mice. The aim of this study was to evaluate the pathogenesis of 2 neurovirulent EHV-1 strains in mice, and to characterize the inflammatory cells and expression of chemokines and the apoptosis marker caspase-3 in the brain of infected mice. C57BL/6J mice were inoculated intranasally with EHV-1 strains A4/72 or A9/92 and evaluated on 1, 2, and 3 days post inoculation (DPI). EHV-1-infected mice showed severe neurological signs at 3 DPI. Ultrastructural analysis revealed numerous viral nucleocapsids and fewer enveloped virions within degenerated and necrotic neurons and in the surrounding neuropil. Histologically, at 3 DPI, there was severe diffuse neuronal degeneration and liquefactive necrosis, prominent microgliosis, and perivascular cuffing composed of CD3(+) cells (T cells) and Iba-1(+) cells (macrophages), mainly in the olfactory bulb and ventral portions of the brain. In these areas, moderate numbers of neuroglial cells expressed CCL5 and CCL2 chemokines. Numerous neurons, including those in less affected areas, were immunolabeled for cleaved caspase-3. In conclusion, neurovirulent EHV-1 strains induced a fulminant necrotizing lymphohistiocytic meningoencephalitis in mice, with microgliosis and expression of chemokines and caspase-3. This model will be useful for understanding the mechanisms underlying the extensive neuropathology induced by these viral infections. (AU)

• Processo FAPESP: 18/23619-0 - Resposta inflamatória no sistema nervoso central de camundongos experimentalmente infectados pelo herpesvirus equino tipo 1
• Beneficiário: Leonardo Pereira Mesquita
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 16/24856-0 - Estudo da resposta inflamatória no sistema nervoso central de camundongos em modelos de infecção com agentes virais e protozoários
• Beneficiário: Paulo César Maiorka
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/09396-2 - Caracterização da resposta imune no sistema nervoso central de camundongos infectados por estirpes altamente neurovirulentas de Herpesvírus Equino tipo 1
• Beneficiário: Leonardo Pereira Mesquita
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado