Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.

Human endogenous retrovirus (HERV) transcripts are known to be highly expressed in cancers, yet their activity in nondiseased tissue is largely unknown. Using the GTEx RNA-seq dataset from normal tissue sampled at autopsy, we characterized individual expression of the recent HERV-K (HML-2) provirus...

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Main Authors: Aidan Burn, Farrah Roy, Michael Freeman, John M Coffin
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-10-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3001826
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author Aidan Burn
Farrah Roy
Michael Freeman
John M Coffin
author_facet Aidan Burn
Farrah Roy
Michael Freeman
John M Coffin
author_sort Aidan Burn
collection DOAJ
description Human endogenous retrovirus (HERV) transcripts are known to be highly expressed in cancers, yet their activity in nondiseased tissue is largely unknown. Using the GTEx RNA-seq dataset from normal tissue sampled at autopsy, we characterized individual expression of the recent HERV-K (HML-2) provirus group across 13,000 different samples of 54 different tissues from 948 individuals. HML-2 transcripts could be identified in every tissue sampled and were elevated in the cerebellum, pituitary, testis, and thyroid. A total of 37 different individual proviruses were expressed in 1 or more tissues, representing all 3 LTR5 subgroups. Nine proviruses were identified as having long terminal repeat (LTR)-driven transcription, 7 of which belonged to the most recent LTR5HS subgroup. Proviruses of different subgroups displayed a bias in tissue expression, which may be associated with differences in transcription factor binding sites in their LTRs. Provirus expression was greater in evolutionarily older proviruses with an earliest shared ancestor of gorilla or older. HML-2 expression was significantly affected by biological sex in 1 tissue, while age and timing of death (Hardy score) had little effect. Proviruses containing intact gag, pro, and env open reading frames (ORFs) were expressed in the dataset, with almost every tissue measured potentially expressing at least 1 intact ORF (gag).
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spelling doaj.art-81705d20b7d34c80a4553b84661889ae2022-12-22T04:35:27ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-10-012010e300182610.1371/journal.pbio.3001826Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.Aidan BurnFarrah RoyMichael FreemanJohn M CoffinHuman endogenous retrovirus (HERV) transcripts are known to be highly expressed in cancers, yet their activity in nondiseased tissue is largely unknown. Using the GTEx RNA-seq dataset from normal tissue sampled at autopsy, we characterized individual expression of the recent HERV-K (HML-2) provirus group across 13,000 different samples of 54 different tissues from 948 individuals. HML-2 transcripts could be identified in every tissue sampled and were elevated in the cerebellum, pituitary, testis, and thyroid. A total of 37 different individual proviruses were expressed in 1 or more tissues, representing all 3 LTR5 subgroups. Nine proviruses were identified as having long terminal repeat (LTR)-driven transcription, 7 of which belonged to the most recent LTR5HS subgroup. Proviruses of different subgroups displayed a bias in tissue expression, which may be associated with differences in transcription factor binding sites in their LTRs. Provirus expression was greater in evolutionarily older proviruses with an earliest shared ancestor of gorilla or older. HML-2 expression was significantly affected by biological sex in 1 tissue, while age and timing of death (Hardy score) had little effect. Proviruses containing intact gag, pro, and env open reading frames (ORFs) were expressed in the dataset, with almost every tissue measured potentially expressing at least 1 intact ORF (gag).https://doi.org/10.1371/journal.pbio.3001826
spellingShingle Aidan Burn
Farrah Roy
Michael Freeman
John M Coffin
Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.
PLoS Biology
title Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.
title_full Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.
title_fullStr Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.
title_full_unstemmed Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.
title_short Widespread expression of the ancient HERV-K (HML-2) provirus group in normal human tissues.
title_sort widespread expression of the ancient herv k hml 2 provirus group in normal human tissues
url https://doi.org/10.1371/journal.pbio.3001826
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