@article{6d0ea03e37534400bc3768f36f7be019,
title = "Murine roseolovirus does not accelerate amyloid-β pathology and human roseoloviruses are not over-represented in Alzheimer disease brains",
abstract = "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-β (Aβ) 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 Aβ deposition. Methods: We utilized the 5XFAD mouse model to test whether MRV induces Aβ deposition in vivo. We also evaluated viral load and neuropathogenesis of MRV infection. To evaluate Aβ 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 Aβ 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 Aβ 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 Aβ plaque formation and AD.",
keywords = "Alzheimer{\textquoteright}s disease, Amyloid-beta, Human roseolovirus, Murine roseolovirus, Neuroinflammation",
author = "Bigley, {Tarin M.} and Monica Xiong and Muhammad Ali and Yun Chen and Chao Wang and Serrano, {Javier Remolina} and Abdallah Eteleeb and Oscar Harari and Liping Yang and Patel, {Swapneel J.} and Carlos Cruchaga and Yokoyama, {Wayne M.} and Holtzman, {David M.}",
note = "Funding Information: This work was supported by NIH grants T32AI106688–07 (T.M.B), T32AR007279–40 (T.M.B.), National Institute on Aging grant AG062027 (M.X.), NIH grants R01AG044546 (C.C.), P01AG003991 (C.C.), P30AG066444 (C.C.), RF1AG053303 (C.C.), RF1AG058501 (C.C.), U01AG058922 (C.C.), R01AG057777 (O.H.), Barnes-Jewish Hospital Foundation (W.M.Y.), R01AG047644 (D.M.H.), and R01NS090934 (D.M.H.). O. H is an Archer Foundation Research Scientist. Funding Information: We thank the Hope Center Alafi Neuroimaging Laboratory for images scanned on a NanoZoomer digital pathology system. We acknowledge Michael Rau, Dr. Brock Summers and John Wulf II at Washington University Center for Cellular Imaging (WUCCI) center for preparing NS samples. NS-TEM imaging was performed in part through the use of WUCCI supported by Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015-505 and CDI-CORE-2019-813) and the Foundation for Barnes-Jewish Hospital (3770 and 4642). Funding Information: D.M.H. is as an inventor on a patent licensed by Washington University to C2N Diagnostics on the therapeutic use of anti-tau antibodies. D.M.H. co-founded and is on the scientific advisory board of C2N Diagnostics. C2N Diagnostics has licensed certain anti-tau antibodies to AbbVie for therapeutic development. D.M.H. is on the scientific advisory board of Denali, Genentech, and Cajal Neurosciences and consults for Eli Lilly. The lab of D.M.H. receives research grants from the National Institutes of Health, Cure Alzheimer{\textquoteright}s Fund, Tau Consortium, the JPB Foundation, Good Ventures, C2N Diagnostics, NextCure, Novartis, and Denali. C.C. receives research support from Biogen, EISAI, Alector and Parabon. C.C. is a member of the advisory board of Vivid genetics, Halia Therapeutics and ADx Healthcare. All other authors declare that they have no competing interests. Funding Information: We thank the Hope Center Alafi Neuroimaging Laboratory for images scanned on a NanoZoomer digital pathology system. We acknowledge Michael Rau, Dr. Brock Summers and John Wulf II at Washington University Center for Cellular Imaging (WUCCI) center for preparing NS samples. NS-TEM imaging was performed in part through the use of WUCCI supported by Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015-505 and CDI-CORE-2019-813) and the Foundation for Barnes-Jewish Hospital (3770 and 4642). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1186/s13024-021-00514-",
language = "English",
volume = "17",
journal = "Molecular neurodegeneration",
issn = "1750-1326",
number = "1",
}