| First Author | Bigley TM | Year | 2022 |
| Journal | Mol Neurodegener | Volume | 17 |
| Issue | 1 | Pages | 10 |
| PubMed ID | 35033173 | Mgi Jnum | J:321354 |
| Mgi Id | MGI:6857149 | Doi | 10.1186/s13024-021-00514-8 |
| Citation | Bigley TM, et al. (2022) Murine roseolovirus does not accelerate amyloid-beta pathology and human roseoloviruses are not over-represented in Alzheimer disease brains. Mol Neurodegener 17(1):10 |
| abstractText | BACKGROUND: The role of viral infection in Alzheimer Disease (AD) pathogenesis is an area of great interest in recent years. Several studies have suggested an association between the human roseoloviruses, HHV-6 and HHV-7, and AD. Amyloid-beta (Abeta) plaques are a hallmark neuropathological finding of AD and were recently proposed to have an antimicrobial function in response to infection. Identifying a causative and mechanistic role of human roseoloviruses in AD has been confounded by limitations in performing in vivo studies. Recent -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Murine roseolovirus (MRV) is a natural murine pathogen that is highly-related to the human roseoloviruses, providing an opportunity to perform well-controlled studies of the impact of roseolovirus on Abeta deposition. METHODS: We utilized the 5XFAD mouse model to test whether MRV induces Abeta deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Abeta interaction with MRV, we performed electron microscopy. RNA-sequencing of a cohort of AD brains compared to control was used to investigate the association between human roseolovirus and AD. RESULTS: We found that 5XFAD mice were susceptible to MRV infection and developed neuroinflammation. Moreover, we demonstrated that Abeta interacts with viral particles in vitro and, subsequent to this interaction, can disrupt infection. Despite this, neither peripheral nor brain infection with MRV increased or accelerated Abeta plaque formation. Moreover, -omics based approaches have demonstrated conflicting associations between human roseoloviruses and AD. Our RNA-sequencing analysis of a cohort of AD brains compared to controls did not show an association between roseolovirus infection and AD. CONCLUSION: Although MRV does infect the brain and cause transient neuroinflammation, our data do not support a role for murine or human roseoloviruses in the development of Abeta plaque formation and AD. |
