tetano
Editor, Senior Moderator
JCI Insight
. 2021 Nov 3;e147170.
doi: 10.1172/jci.insight.147170. Online ahead of print.
SARS-CoV-2 infection mediates differential expression of human endogenous retroviruses and long interspersed nuclear elements
Jez L Marston[SUP] 1 [/SUP], Matthew Greenig[SUP] 1 [/SUP], Manvendra Singh[SUP] 2 [/SUP], Matthew L Bendall[SUP] 1 [/SUP], Rodrigo Rr Duarte[SUP] 1 [/SUP], Cédric Feschotte[SUP] 2 [/SUP], Luis P Iñiguez[SUP] 1 [/SUP], Douglas F Nixon[SUP] 1 [/SUP]
Affiliations
Abstract
Severe respiratory coronavirus 2 (SARS-CoV-2) promotes an imbalanced host response which underlies the development and severity of COVID-19. Infections with viruses are known to modulate transposable elements (TEs) which can exert downstream effects by modulating host gene expression, innate immune sensing, or activities encoded by their protein products. We investigated the impact of SARS-CoV-2 infection on TE expression using RNA-seq data from cell lines and from primary patient samples. Using a bioinformatic tool, Telescope, we showed that SARS-CoV-2 infection led to up- or down-regulation of TE transcripts, a subset of which differed from cells infected with SARS, MERS, RSV, HPIV3 or IAV. Differential expression of key retroelements specifically identified distinct virus families such as coronaviridae, with unique retroelement expression subdividing viral species. Analysis of ChIP-seq data shows that TEs differentially expressed in SARS-CoV-2 infection are enriched for binding sites for TFs involved in immune responses and for pioneer transcription factors. In COVID-19 patient samples, there was a significant TE overexpression in bronchoalveolar lavage fluid and downregulation in peripheral blood mononuclear cells. Thus, while the host gene transcriptome is altered by infection with SARS-CoV-2, the retrotranscriptome may contain the most distinctive features of the cellular response to SARS-CoV-2 infection.
Keywords: COVID-19; Infectious disease; Innate immunity.
. 2021 Nov 3;e147170.
doi: 10.1172/jci.insight.147170. Online ahead of print.
SARS-CoV-2 infection mediates differential expression of human endogenous retroviruses and long interspersed nuclear elements
Jez L Marston[SUP] 1 [/SUP], Matthew Greenig[SUP] 1 [/SUP], Manvendra Singh[SUP] 2 [/SUP], Matthew L Bendall[SUP] 1 [/SUP], Rodrigo Rr Duarte[SUP] 1 [/SUP], Cédric Feschotte[SUP] 2 [/SUP], Luis P Iñiguez[SUP] 1 [/SUP], Douglas F Nixon[SUP] 1 [/SUP]
Affiliations
- PMID: 34731091
- DOI: 10.1172/jci.insight.147170
Abstract
Severe respiratory coronavirus 2 (SARS-CoV-2) promotes an imbalanced host response which underlies the development and severity of COVID-19. Infections with viruses are known to modulate transposable elements (TEs) which can exert downstream effects by modulating host gene expression, innate immune sensing, or activities encoded by their protein products. We investigated the impact of SARS-CoV-2 infection on TE expression using RNA-seq data from cell lines and from primary patient samples. Using a bioinformatic tool, Telescope, we showed that SARS-CoV-2 infection led to up- or down-regulation of TE transcripts, a subset of which differed from cells infected with SARS, MERS, RSV, HPIV3 or IAV. Differential expression of key retroelements specifically identified distinct virus families such as coronaviridae, with unique retroelement expression subdividing viral species. Analysis of ChIP-seq data shows that TEs differentially expressed in SARS-CoV-2 infection are enriched for binding sites for TFs involved in immune responses and for pioneer transcription factors. In COVID-19 patient samples, there was a significant TE overexpression in bronchoalveolar lavage fluid and downregulation in peripheral blood mononuclear cells. Thus, while the host gene transcriptome is altered by infection with SARS-CoV-2, the retrotranscriptome may contain the most distinctive features of the cellular response to SARS-CoV-2 infection.
Keywords: COVID-19; Infectious disease; Innate immunity.