Development of a transgenic murine model for human herpesvirus 6A infection and study of the mechanisms of induction of neuroinflammation
type: Dataset
contact point: Organization
  fn: CCSD
keyword: neuroinflammation
keyword: souris
keyword: sclerose-en-plaques
keyword: animal-model
keyword: multiple-sclerosis
keyword: mouse
keyword: theses
keyword: human-endogenous-retrovirus
keyword: encephalite
keyword: sdvbalife-sciences-q-bioanimal-biology
keyword: modele-animal
keyword: herpesvirus
keyword: retrovirus-endogene-humain
keyword: infoeu-reposemanticsdoctoralthesis
keyword: hhv-6
keyword: cd46
keyword: encephalitis
keyword: sdvbclife-sciences-q-biocellular-biology
landing page: https://theses.hal.science/tel-00998378
description: Human herpesvirus (HHV) 6 is a widely spread betaherpesvirus, which has been associated to several neuroinflammatory diseases, such as encephalitis or multiple sclerosis (MS). However, the mechanisms explaining the neuropathology induced by the two species of HHV-6, HHV-6A and HHV-6B, remain to be elucidated. Moreover, the lack of small animal model for HHV-6 infection has considerably hampered the study of viral pathogenesis. In this context, we have generated several lines of mice expressing the human CD46 protein, identified as a cellular receptor for HHV-6, and characterized the infection. We demonstrated that DNA of HHV-6A, but not HHV-6B, can persist in the brain of CD46 transgenic mice for several months after intracranial injection. Moreover our results show that HHV-6A induces chemokine secretion by in vitro cultured murine brain cells and provokes leucocyte infiltration in the brain of infected mice. Finally, HHV-6A, but not HHV-6B, could activate cellular responses in murine cells through binding to toll-like receptor 9. In collaboration with the team of P. Marche in Grenoble, we then showed that HHV-6A and HHV-6B infection induce the expression of envelope genes from human endogenous retrovirus W (HERV-W) in human blood mononucleated cells and human neural cell lines. Envelope proteins of HERV-W are known to exhibit strong pro-inflammatory properties and were associated to various autoimmune diseases, including multiple sclerosis. HHV-6A and HHV-6B could therefore participate in the development of inflammatory disorders via the activation of these HERV genes. Altogether this work supports the hypothesis of a link between HHV-6 infection neuroinflammation and opens new perspectives in the study of the mechanisms potentially involved.
identifier: NNT: 2013ENSL0813
issued: 2026-05-05T09:56:18.425056
language: fr
modified: 2026-05-05T09:56:18.425060

Development of a transgenic murine model for human herpesvirus 6A infection and study of the mechanisms of induction of neuroinflammation
type: Distribution
access URL: https://theses.hal.science/tel-00998378
format: HTML
issued: 2026-05-05T09:56:18.429391
modified: 2026-05-05T09:56:18.404207

test_moissonnage_selune
type: Agent