A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex

Abstract There is increasing evidence that endogenous retroviruses (ERVs) play a significant role in central nervous system diseases, including amyotrophic lateral sclerosis (ALS). Studies of ALS have consistently identified retroviral enzyme reverse transcriptase activity in patients. Evidence indi...

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Autores principales:	Ashley R. Jones, Alfredo Iacoangeli, Brett N. Adey, Harry Bowles, Aleksey Shatunov, Claire Troakes, Jeremy A. Garson, Adele L. McCormick, Ammar Al-Chalabi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fa585c9e6ffc49b992d0f81a36717fb6
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spelling	oai:doaj.org-article:fa585c9e6ffc49b992d0f81a36717fb62021-12-02T18:30:40ZA HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex10.1038/s41598-021-93742-32045-2322https://doaj.org/article/fa585c9e6ffc49b992d0f81a36717fb62021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93742-3https://doaj.org/toc/2045-2322Abstract There is increasing evidence that endogenous retroviruses (ERVs) play a significant role in central nervous system diseases, including amyotrophic lateral sclerosis (ALS). Studies of ALS have consistently identified retroviral enzyme reverse transcriptase activity in patients. Evidence indicates that ERVs are the cause of reverse transcriptase activity in ALS, but it is currently unclear whether this is due to a specific ERV locus or a family of ERVs. We employed a combination of bioinformatic methods to identify whether specific ERVs or ERV families are associated with ALS. Using the largest post-mortem RNA-sequence datasets available we selectively identified ERVs that closely resembled full-length proviruses. In the discovery dataset there was one ERV locus (HML6_3p21.31c) that showed significant increased expression in post-mortem motor cortex tissue after multiple-testing correction. Using six replication post-mortem datasets we found HML6_3p21.31c was consistently upregulated in ALS in motor cortex and cerebellum tissue. In addition, HML6_3p21.31c showed significant co-expression with cytokine binding and genes involved in EBV, HTLV-1 and HIV type-1 infections. There were no significant differences in ERV family expression between ALS and controls. Our results support the hypothesis that specific ERV loci are involved in ALS pathology.Ashley R. JonesAlfredo IacoangeliBrett N. AdeyHarry BowlesAleksey ShatunovClaire TroakesJeremy A. GarsonAdele L. McCormickAmmar Al-ChalabiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ashley R. Jones Alfredo Iacoangeli Brett N. Adey Harry Bowles Aleksey Shatunov Claire Troakes Jeremy A. Garson Adele L. McCormick Ammar Al-Chalabi A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex
description	Abstract There is increasing evidence that endogenous retroviruses (ERVs) play a significant role in central nervous system diseases, including amyotrophic lateral sclerosis (ALS). Studies of ALS have consistently identified retroviral enzyme reverse transcriptase activity in patients. Evidence indicates that ERVs are the cause of reverse transcriptase activity in ALS, but it is currently unclear whether this is due to a specific ERV locus or a family of ERVs. We employed a combination of bioinformatic methods to identify whether specific ERVs or ERV families are associated with ALS. Using the largest post-mortem RNA-sequence datasets available we selectively identified ERVs that closely resembled full-length proviruses. In the discovery dataset there was one ERV locus (HML6_3p21.31c) that showed significant increased expression in post-mortem motor cortex tissue after multiple-testing correction. Using six replication post-mortem datasets we found HML6_3p21.31c was consistently upregulated in ALS in motor cortex and cerebellum tissue. In addition, HML6_3p21.31c showed significant co-expression with cytokine binding and genes involved in EBV, HTLV-1 and HIV type-1 infections. There were no significant differences in ERV family expression between ALS and controls. Our results support the hypothesis that specific ERV loci are involved in ALS pathology.
format	article
author	Ashley R. Jones Alfredo Iacoangeli Brett N. Adey Harry Bowles Aleksey Shatunov Claire Troakes Jeremy A. Garson Adele L. McCormick Ammar Al-Chalabi
author_facet	Ashley R. Jones Alfredo Iacoangeli Brett N. Adey Harry Bowles Aleksey Shatunov Claire Troakes Jeremy A. Garson Adele L. McCormick Ammar Al-Chalabi
author_sort	Ashley R. Jones
title	A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex
title_short	A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex
title_full	A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex
title_fullStr	A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex
title_full_unstemmed	A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex
title_sort	hml6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fa585c9e6ffc49b992d0f81a36717fb6
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A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex

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