Human endogenous retroviruses of the HERV-K (HML-2) family are expressed in the brain of healthy individuals and modify the composition of the brain-infiltrating immune cells

Tapio Nevalainen; Arttu Autio; Mikko Hurme

doi:10.1016/j.heliyon.2023.e21283

Human endogenous retroviruses of the HERV-K (HML-2) family are expressed in the brain of healthy individuals and modify the composition of the brain-infiltrating immune cells

Tapio Nevalainen^*
, Arttu Autio
, Mikko Hurme

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

4 Citations (Scopus)

13 Downloads (Pure)

Abstract

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections in the human genome. RNA expression of individual HERVs has frequently been observed in various pathologic conditions, but some activity can also be seen in healthy individuals, e.g. in the blood. To quantitate the basal expression levels of HERVs in the brain, we now used high-throughput sequencing-based metagenomic analysis to characterize the expression profiles of the HERV-K (HML-2) family proviruses in different brain regions of healthy brain tissue. To this end, RNA-seq data from the Genotype-Tissue Expression (GTEx) project was used. The GTEx project is a public resource to study tissue-specific gene expression and regulation, consisting of a large selection of sequenced samples from different tissues. The GTEx data used in this study consisted of 378 samples taken from 13 brain regions from 55 individuals. The data demonstrated that out of 99 intact proviruses in the family 58 were expressed, but the expression profiles were highly divergent and there were no significant differences in the expression profiles between the various anatomic regions of the brain. It is known that the brain contains a variety of infiltrating immune cells, which are probably of great importance both in the normal defense mechanisms as well as in the various pathogenic processes. Digital cytometry (CIBERSORTx) was used to quantify the proportions of the infiltrating immune cells in the same brain samples. Six most abundant (>5 % of the total population) cell types were observed to be CD4 memory resting T cells, M0 macrophages, plasma cells, CD8 T cells, CD4 memory activated T cells, and monocytes. Analysis of the correlations between the individual HERVs and infiltrating cell types indicated that a cluster of 6 HERVs had a notable correlation signature between T cell type infiltrating cell proportions and HERV RNA expression intensity. The correlations between inflammatory type infiltrating cells were negative or weak. Taken together, these data indicate that the expression of HERVs is associated with a T cell type immunity.

Original language	English
Article number	e21283
Number of pages	10
Journal	Heliyon
Volume	9
Issue number	11
DOIs	https://doi.org/10.1016/j.heliyon.2023.e21283
Publication status	Published - 2023
Publication type	A1 Journal article-refereed

Funding

The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health (commonfund.nih.gov/GTEx). Additional funds were provided by the NCI , NHGRI , NHLBI , NIDA , NIMH , and NINDS . Donors were enrolled at Biospecimen Source Sites funded by NCI\Leidos Biomedical Research, Inc. Subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute ( 10XS171 ), and Science Care, Inc. ( X10S172 ). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract ( HHSN268201000029C ) to the The Broad Institute , Inc. Biorepository operations were funded through a Leidos Biomedical Research, Inc. Subcontract to Van Andel Research Institute ( 10ST1035 ). Additional data repository and project management were provided by Leidos Biomedical Research, Inc. (HHSN261200800001E). The Brain Bank was supported supplements to University of Miami grant DA006227 . Statistical Methods development grants were made to the University of Geneva ( MH090941 & MH101814 ), the University of Chicago ( MH090951 , MH090937 , MH101825 , & MH101820 ), the University of North Carolina - Chapel Hill ( MH090936 ), North Carolina State University ( MH101819 ), Harvard University ( MH090948 ), Stanford University ( MH101782 ), Washington University ( MH101810 ), and to the University of Pennsylvania ( MH101822 ). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000424. v8. p2. This work was financially supported by research funding provided by the Tampere Tuberculosis foundation (MH); the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (MH); the Finnish Cultural Foundation, Pirkanmaa Regional Fund (TN); the Finnish Cultural Foundation (AA); and the Emil Aaltonen Foundation (AA).The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health (commonfund.nih.gov/GTEx). Additional funds were provided by the NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Donors were enrolled at Biospecimen Source Sites funded by NCI\Leidos Biomedical Research, Inc. Subcontracts to the National Disease Research Interchange (10XS170), Roswell Park Cancer Institute (10XS171), and Science Care, Inc. (X10S172). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to the The Broad Institute, Inc. Biorepository operations were funded through a Leidos Biomedical Research, Inc. Subcontract to Van Andel Research Institute (10ST1035). Additional data repository and project management were provided by Leidos Biomedical Research, Inc. (HHSN261200800001E). The Brain Bank was supported supplements to University of Miami grant DA006227. Statistical Methods development grants were made to the University of Geneva (MH090941 & MH101814), the University of Chicago (MH090951, MH090937, MH101825, & MH101820), the University of North Carolina - Chapel Hill (MH090936), North Carolina State University (MH101819), Harvard University (MH090948), Stanford University (MH101782), Washington University (MH101810), and to the University of Pennsylvania (MH101822). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000424. v8. p2. This work was financially supported by research funding provided by the Tampere Tuberculosis foundation (MH); the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (MH); the Finnish Cultural Foundation , Pirkanmaa Regional Fund (TN); the Finnish Cultural Foundation ( AA ); and the Emil Aaltonen Foundation ( AA ).

Funders	Funder number
Broad Institute , Inc.
Broad Institute, Inc.	HHSN261200800001E, 10ST1035
National Disease Research Interchange	10XS170
Science Care, Inc.	X10S172
National Institutes of Health	commonfund.nih.gov/GTEx
National Institute of Mental Health
National Institute on Drug Abuse
National Heart, Lung, and Blood Institute (NHLBI)
National Human Genome Research Institute
National Cancer Institute	HHSN268201000029C
National Institute of Neurological Disorders and Stroke (NINDS)
Roswell Park Comprehensive Cancer Center	10XS171
Stanford University	MH101782
University of Miami	DA006227
University of Pennsylvania	MH101822, phs000424
Harvard University	MH090948
University of Chicago	MH101825, MH090951, MH101820, MH090937
North Carolina State University	MH101819
University of Washington	MH101810
University of North Carolina at Chapel Hill	MH090936
Suomen Kulttuurirahasto
Emil Aaltosen Säätiö
Kulttuurirahaston Pirkanmaan rahasto
Université de Genève / Département d'histoire du droit et des doctrines juridiques et politiques	MH101814, MH090941
Tampereen tuberkuloosisäätiö

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Brain
CIBERSORTx
GTEx
HERV-K
T cells

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

General

Access to Document

10.1016/j.heliyon.2023.e21283Licence: CC BY-NC-ND

1-s2.0-S2405844023084918-mainFinal published version, 2.76 MBLicence: CC BY-NC-ND

https://urn.fi/URN:NBN:fi:tuni-202311089483Licence: CC BY-NC-ND

Cite this

@article{7a427108e363490486ed713cedab622d,

title = "Human endogenous retroviruses of the HERV-K (HML-2) family are expressed in the brain of healthy individuals and modify the composition of the brain-infiltrating immune cells",

abstract = "Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections in the human genome. RNA expression of individual HERVs has frequently been observed in various pathologic conditions, but some activity can also be seen in healthy individuals, e.g. in the blood. To quantitate the basal expression levels of HERVs in the brain, we now used high-throughput sequencing-based metagenomic analysis to characterize the expression profiles of the HERV-K (HML-2) family proviruses in different brain regions of healthy brain tissue. To this end, RNA-seq data from the Genotype-Tissue Expression (GTEx) project was used. The GTEx project is a public resource to study tissue-specific gene expression and regulation, consisting of a large selection of sequenced samples from different tissues. The GTEx data used in this study consisted of 378 samples taken from 13 brain regions from 55 individuals. The data demonstrated that out of 99 intact proviruses in the family 58 were expressed, but the expression profiles were highly divergent and there were no significant differences in the expression profiles between the various anatomic regions of the brain. It is known that the brain contains a variety of infiltrating immune cells, which are probably of great importance both in the normal defense mechanisms as well as in the various pathogenic processes. Digital cytometry (CIBERSORTx) was used to quantify the proportions of the infiltrating immune cells in the same brain samples. Six most abundant (>5 \% of the total population) cell types were observed to be CD4 memory resting T cells, M0 macrophages, plasma cells, CD8 T cells, CD4 memory activated T cells, and monocytes. Analysis of the correlations between the individual HERVs and infiltrating cell types indicated that a cluster of 6 HERVs had a notable correlation signature between T cell type infiltrating cell proportions and HERV RNA expression intensity. The correlations between inflammatory type infiltrating cells were negative or weak. Taken together, these data indicate that the expression of HERVs is associated with a T cell type immunity.",

keywords = "Brain, CIBERSORTx, GTEx, HERV-K, T cells",

author = "Tapio Nevalainen and Arttu Autio and Mikko Hurme",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

doi = "10.1016/j.heliyon.2023.e21283",

language = "English",

volume = "9",

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T1 - Human endogenous retroviruses of the HERV-K (HML-2) family are expressed in the brain of healthy individuals and modify the composition of the brain-infiltrating immune cells

AU - Nevalainen, Tapio

AU - Autio, Arttu

AU - Hurme, Mikko

PY - 2023

Y1 - 2023

N2 - Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections in the human genome. RNA expression of individual HERVs has frequently been observed in various pathologic conditions, but some activity can also be seen in healthy individuals, e.g. in the blood. To quantitate the basal expression levels of HERVs in the brain, we now used high-throughput sequencing-based metagenomic analysis to characterize the expression profiles of the HERV-K (HML-2) family proviruses in different brain regions of healthy brain tissue. To this end, RNA-seq data from the Genotype-Tissue Expression (GTEx) project was used. The GTEx project is a public resource to study tissue-specific gene expression and regulation, consisting of a large selection of sequenced samples from different tissues. The GTEx data used in this study consisted of 378 samples taken from 13 brain regions from 55 individuals. The data demonstrated that out of 99 intact proviruses in the family 58 were expressed, but the expression profiles were highly divergent and there were no significant differences in the expression profiles between the various anatomic regions of the brain. It is known that the brain contains a variety of infiltrating immune cells, which are probably of great importance both in the normal defense mechanisms as well as in the various pathogenic processes. Digital cytometry (CIBERSORTx) was used to quantify the proportions of the infiltrating immune cells in the same brain samples. Six most abundant (>5 % of the total population) cell types were observed to be CD4 memory resting T cells, M0 macrophages, plasma cells, CD8 T cells, CD4 memory activated T cells, and monocytes. Analysis of the correlations between the individual HERVs and infiltrating cell types indicated that a cluster of 6 HERVs had a notable correlation signature between T cell type infiltrating cell proportions and HERV RNA expression intensity. The correlations between inflammatory type infiltrating cells were negative or weak. Taken together, these data indicate that the expression of HERVs is associated with a T cell type immunity.

AB - Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections in the human genome. RNA expression of individual HERVs has frequently been observed in various pathologic conditions, but some activity can also be seen in healthy individuals, e.g. in the blood. To quantitate the basal expression levels of HERVs in the brain, we now used high-throughput sequencing-based metagenomic analysis to characterize the expression profiles of the HERV-K (HML-2) family proviruses in different brain regions of healthy brain tissue. To this end, RNA-seq data from the Genotype-Tissue Expression (GTEx) project was used. The GTEx project is a public resource to study tissue-specific gene expression and regulation, consisting of a large selection of sequenced samples from different tissues. The GTEx data used in this study consisted of 378 samples taken from 13 brain regions from 55 individuals. The data demonstrated that out of 99 intact proviruses in the family 58 were expressed, but the expression profiles were highly divergent and there were no significant differences in the expression profiles between the various anatomic regions of the brain. It is known that the brain contains a variety of infiltrating immune cells, which are probably of great importance both in the normal defense mechanisms as well as in the various pathogenic processes. Digital cytometry (CIBERSORTx) was used to quantify the proportions of the infiltrating immune cells in the same brain samples. Six most abundant (>5 % of the total population) cell types were observed to be CD4 memory resting T cells, M0 macrophages, plasma cells, CD8 T cells, CD4 memory activated T cells, and monocytes. Analysis of the correlations between the individual HERVs and infiltrating cell types indicated that a cluster of 6 HERVs had a notable correlation signature between T cell type infiltrating cell proportions and HERV RNA expression intensity. The correlations between inflammatory type infiltrating cells were negative or weak. Taken together, these data indicate that the expression of HERVs is associated with a T cell type immunity.

KW - Brain

KW - CIBERSORTx

KW - GTEx

KW - HERV-K

KW - T cells

U2 - 10.1016/j.heliyon.2023.e21283

DO - 10.1016/j.heliyon.2023.e21283

M3 - Article

AN - SCOPUS:85174740841

SN - 2405-8440

VL - 9

JO - Heliyon

JF - Heliyon

IS - 11

M1 - e21283

ER -

Human endogenous retroviruses of the HERV-K (HML-2) family are expressed in the brain of healthy individuals and modify the composition of the brain-infiltrating immune cells

Abstract

Funding

UN SDGs

Keywords

Publication forum classification

ASJC Scopus subject areas

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