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dc.contributor.authorDembny, Paul
dc.contributor.authorGolenbock, Douglas T.
dc.contributor.authorLehnardt, Seija
dc.date2022-08-11T08:09:56.000
dc.date.accessioned2022-08-23T16:49:20Z
dc.date.available2022-08-23T16:49:20Z
dc.date.issued2020-04-09
dc.date.submitted2020-05-13
dc.identifier.citation<p>Dembny P, Newman AG, Singh M, Hinz M, Szczepek M, Krüger C, Adalbert R, Dzaye O, Trimbuch T, Wallach T, Kleinau G, Derkow K, Richard BC, Schipke C, Scheidereit C, Stachelscheid H, Golenbock D, Peters O, Coleman M, Heppner FL, Scheerer P, Tarabykin V, Ruprecht K, Izsvák Z, Mayer J, Lehnardt S. Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors. JCI Insight. 2020 Apr 9;5(7):131093. doi: 10.1172/jci.insight.131093. PMID: 32271161. <a href="https://doi.org/10.1172/jci.insight.131093">Link to article on publisher's site</a></p>
dc.identifier.issn2379-3708 (Linking)
dc.identifier.doi10.1172/jci.insight.131093
dc.identifier.pmid32271161
dc.identifier.urihttp://hdl.handle.net/20.500.14038/41441
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractAlthough human endogenous retroviruses (HERVs) represent a substantial proportion of the human genome and some HERVs, such as HERV-K(HML-2), are reported to be involved in neurological disorders, little is known about their biological function. We report that RNA from an HERV-K(HML-2) envelope gene region binds to and activates human Toll-like receptor (TLR) 8, as well as murine Tlr7, expressed in neurons and microglia, thereby causing neurodegeneration. HERV-K(HML-2) RNA introduced into the cerebrospinal fluid (CSF) of either C57BL/6 wild-type mice or APPPS1 mice, a mouse model for Alzheimer's disease (AD), resulted in neurodegeneration and microglia accumulation. Tlr7-deficient mice were protected against neurodegenerative effects but were resensitized toward HERV-K(HML-2) RNA when neurons ectopically expressed murine Tlr7 or human TLR8. Transcriptome data sets of human AD brain samples revealed a distinct correlation of upregulated HERV-K(HML-2) and TLR8 RNA expression. HERV-K(HML-2) RNA was detectable more frequently in CSF from individuals with AD compared with controls. Our data establish HERV-K(HML-2) RNA as an endogenous ligand for species-specific TLRs 7/8 and imply a functional contribution of human endogenous retroviral transcripts to neurodegenerative processes, such as AD.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=32271161&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1172/jci.insight.131093
dc.subjectAlzheimer’s disease
dc.subjectImmunology
dc.subjectInnate immunity
dc.subjectNeurodegeneration
dc.subjectNeuroscience
dc.subjectImmunology and Infectious Disease
dc.subjectNervous System Diseases
dc.subjectNeuroscience and Neurobiology
dc.subjectViruses
dc.titleHuman endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors
dc.typeJournal Article
dc.source.journaltitleJCI insight
dc.source.volume5
dc.source.issue7
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4220
dc.identifier.contextkey17724373
html.description.abstract<p>Although human endogenous retroviruses (HERVs) represent a substantial proportion of the human genome and some HERVs, such as HERV-K(HML-2), are reported to be involved in neurological disorders, little is known about their biological function. We report that RNA from an HERV-K(HML-2) envelope gene region binds to and activates human Toll-like receptor (TLR) 8, as well as murine Tlr7, expressed in neurons and microglia, thereby causing neurodegeneration. HERV-K(HML-2) RNA introduced into the cerebrospinal fluid (CSF) of either C57BL/6 wild-type mice or APPPS1 mice, a mouse model for Alzheimer's disease (AD), resulted in neurodegeneration and microglia accumulation. Tlr7-deficient mice were protected against neurodegenerative effects but were resensitized toward HERV-K(HML-2) RNA when neurons ectopically expressed murine Tlr7 or human TLR8. Transcriptome data sets of human AD brain samples revealed a distinct correlation of upregulated HERV-K(HML-2) and TLR8 RNA expression. HERV-K(HML-2) RNA was detectable more frequently in CSF from individuals with AD compared with controls. Our data establish HERV-K(HML-2) RNA as an endogenous ligand for species-specific TLRs 7/8 and imply a functional contribution of human endogenous retroviral transcripts to neurodegenerative processes, such as AD.</p>
dc.identifier.submissionpathoapubs/4220
dc.contributor.departmentDivision of Infectious Diseases and Immunology, Department of Medicine


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