Full text
| |
| Author(s): |
Leonardo Pereira Mesquita
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) |
| Defense date: | 2016-09-23 |
| Examining board members: |
Paulo César Maiorka;
Claudia Madalena Cabrera Mori;
Frederico Azevedo da Costa Pinto;
Edviges Maristela Pituco;
Mary Susan Varaschin
|
| Advisor: | Paulo César Maiorka |
| Abstract | |
The present work comprises the study of immune and inflammatory responses in the central nervous system (CNS) of mice or deer mice (Peromyscus maniculatus) during infection by two different neurotropic viruses, the vesicular stomatitis virus (VSV) and bovine herpesvirus type 5 (BoHV-5). In the first part, the role of CNS resident cells regarding chemokine expression in deer mice infected with VSV was evaluated. Here, we demonstrated that during vesicular stomatitis New Jersey virus (VSNJV) encephalitis in deer mice, chemokines RANTES and MCP-1 are expressed only in the olfactory bulb (OB), where the virus was restricted. This chemokine expression was followed by the influx of inflammatory cells to the OB later in the course of acute disease. Neurons, astrocytes and microglia expressed RANTES, whereas MCP-1 was expressed by neurons and astrocytes. Although astrocytes and microglia responded to VSNJV infection by expressing chemokines, neurons were the predominantly infected cell type. Therefore, infected neurons may have a critical role in initiating an immune response in the OB. The signaling between neurons and other CNS resident cells is most likely the mechanism by which astrocytes and microglia are activated during the course of VSV encephalitis. Our results also indicate that the expression of RANTES and MCP-1 in the OB of deer mice infected with VSNJV might help prevent the spread of VSNJV to other areas of CNS. In the second part of the study, the susceptibility of isogenic BALB/c mice to BoHV-5 infection was evaluated in different days post-inoculation (DPI). BoHV-5, when inoculated through intracranial route, was able to infect and replicate within the CNS of BALB/c mice. However, until the evaluated time (15 DPI), the mice was able to survive without showing prominent neurological signs. The infection was accompanied by an important Th1 immune response, with a significant expression of the cytokines IFN-Y and TNF-α, and chemokine CCL-2. The expression of these cytokines and chemokines was detected mainly on the early course of infection (3 and 4 DPI), and was followed by a meningoencephalitis with perivascular cuffing and periventriculitis, composed mainly by macrophages and lymphocytes. After the expression of cytokines and chemokine, the mice were able to curb BoHV-5 acute infection, since viable viral particles were not detected after 6 DPI. However, BoHV-5 was able to infect the trigeminal ganglia, since a large number of BoHV-5 DNA copies was detected on 3 DPI, which was confirmed by the presence of viral antigens within the cytoplasm of neurons in the trigeminal ganglia of infected BALB/c mice (AU) | |
| FAPESP's process: | 13/00629-6 - Evaluation of Immune and Inflammatory Responses in Experimentally Induced Encephalitis in Mice by Bovine Herpesvirus 5 (BHV-5) and Vesicular Estomatitis Virus (VSV) Infection. |
| Grantee: | Leonardo Pereira Mesquita |
| Support Opportunities: | Scholarships in Brazil - Doctorate |