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Characterization of immune response in the central nervous system of mice infected with highly neurovirulent strains of Equid Herpesvirus type 1

Grant number: 16/09396-2
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2016
Effective date (End): December 08, 2020
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Animal Pathology
Principal Investigator:Paulo César Maiorka
Grantee:Leonardo Pereira Mesquita
Home Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):18/23619-0 - Inflammatory response in the central nervous system of mice experimentally infected with Equid Herpesvirus type 1, BE.EP.PD


Equid herpesvirus type 1 (EHV-1) is a potential emerging pathogen which is recognized worldwide as a cause of neurological disease in equine. However, a fatal and acute meningoencephalitis associated with extensive neuronal necrosis caused by EHV-1 have been reported in other animal species. The morphological changes in the central nervous system (CNS), as well as the disease outcome in these aberrant hosts are similar to those found in animal models developed by our research group. Little is known about the immune response in CNS, mainly regarding the role of inflammatory mediators and cells during development of EHV-1 encephalitis. Therefore, the aim of the present project is to characterize the innate immune response and the pathological events in the CNS of C57BL/6 and C57BL/6 nude mice, as well as to evaluate the role of T cells during the encephalitis caused by highly neurovirulent EHV-1 strains (A4/72 and A9/92). For this purpose, the expression of proinflammatory cytokines (IL-1², IL-6, IL-12, IFN-³ and TNF-±), chemokine (CCL-2) and Toll-like receptors (TLR3 and TLR9) will be evaluated by gene expression in the CNS. Inflammatory cells such as TCD4+ and TCD8+ cells, macrophages (M1 and M2 phenotype), microglia and dendritic cells will phenotypically characterized by flow cytometry. During encephalitis, an evaluation of the inflammatory changes will be performed and correlated with the distribution of EHV-1 within the CNS, which will be evaluated by immunohistochemistry and absolute quantification by qPCR. The role of T cells during EHV-1 infection will be evaluated by the comparison between different isogenic lineages of C57BL/6 and C57BL/6 nude mice (athymic) since the latter are deprived of T cells. The data obtained here will clarify important aspects of innate immune response and mechanisms of neuroinflammation during a lethal and acute disease caused by EHV-1, a potential emerging pathogen.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MESQUITA, LEONARDO PEREIRA; AREVALO, ANDRESSA FERRARI; ZANATTO, DENNIS A.; MIYASHIRO, SAMANTHA IYE; SEQUETIN CUNHA, ELENICE MARIA; CUSTODIO DE SOUZA, MARIA DO CARMO; CASSARO VILLALOBOS, ELIANA MONTEFORTE; CABRERA MORI, CLAUDIA MADALENA; MAIORKA, PAULO CESAR; MORI, ENIO. Equine herpesvirus type 1 induces both neurological and respiratory disease in Syrian hamsters. Veterinary Microbiology, v. 203, p. 117-124, MAY 2017. Web of Science Citations: 1.

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