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Le virus herpès simplex de type 1 et la réponse immunitaire cérébrale innée
| Content Provider | Semantic Scholar |
|---|---|
| Author | Boivin, Nicolas |
| Copyright Year | 2013 |
| Abstract | Neurovirulence is one of the most important biological properties of herpes simplex virus (HSV). HSV can reach the central nervous system (CNS) and cause encephalitis. This infection triggers an inflammatory response leading to the infiltration of peripheral immune cells into the CNS. Thus, encephalitis is the most devastating infection associated with HSV-1 and is one of the most frequent causes of sporadic and potentially fatal viral encephalitis in developed countries. Despite the different animal models available to study HSV-1 encephalitis, the complexity of the CNS and its immune response limits our understanding of this disease. The main objective of this thesis is to better understand the innate immune response involved in the different signaling pathways implicated in HSV recognition. Studies performed during the course of this Ph. D. thesis have highlighted the key role of IFN-p, of Toll-like receptor (TLR)3 and 9 signaling pathways as well as of TRIF and IPS-1 adaptor proteins. Mouse pretreatment with a TLR3 agonist creates a hostile pro-inflammatory environment for the initial virus replication, thereby limiting the production of cytokines and the viral replication at latter time after infection. Moreover, stimulation with a TLR9 agonist is beneficial before the infection, but needs to be controlled following the infection. As previously suggested, IFN-P may exert a beneficial role against HSV-1 infection, but the dosing regimen and time of initiation of treatment after the infection may have a strong impact on viral replication and mice survival. Finaly, both adaptor proteins, TRIF and IPS-1, play an important role in the innate immune response leading to the production of IFN-p, although TRIF affects more importantly the early viral replication than IPS-1. Thus, during this Ph. D., several experimental models were developed to better understand the innate immune response in the CNS during herpes simplex encephalitis, the recruitment of différents immune cells as well as to better characterize the role played by IFN-p. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://corpus.ulaval.ca/jspui/bitstream/20.500.11794/24735/1/29711.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
