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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 9
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: VETERINARY PATHOLOGY; v. 58, n. 6, p. 1075-1085, NOV 2021.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 18/23619-0 - Inflammatory response in the central nervous system of mice experimentally infected with Equid Herpesvirus type 1
Grantee:Leonardo Pereira Mesquita
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 16/24856-0 - Characterization of inflammatory response in the central nervous system in mouse models of viral and protozoan infection
Grantee:Paulo César Maiorka
Support Opportunities: Regular Research Grants
FAPESP's process: 16/09396-2 - Characterization of immune response in the central nervous system of mice infected with highly neurovirulent strains of Equid Herpesvirus type 1
Grantee:Leonardo Pereira Mesquita
Support Opportunities: Scholarships in Brazil - Post-Doctoral