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SARS-CoV-2 infection mediates differential expression of human endogenous retroviruses and long interspersed nuclear elements.
JCI Insight. 2021 12 22; 6(24)JI

Abstract

SARS-CoV-2 promotes an imbalanced host response that 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 bioinformatics tool, Telescope, we showed that SARS-CoV-2 infection led to upregulation or downregulation of TE transcripts, a subset of which differed from cells infected with SARS, Middle East respiratory syndrome coronavirus (MERS-CoV or MERS), influenza A virus (IAV), respiratory syncytial virus (RSV), and human parainfluenza virus type 3 (HPIV3). 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 showed that TEs differentially expressed in SARS-CoV-2 infection were enriched for binding sites for transcription factors involved in immune responses and for pioneer transcription factors. In samples from patients with COVID-19, there was significant TE overexpression in bronchoalveolar lavage fluid and downregulation in PBMCs. Thus, although 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.

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Authors+Show Affiliations

Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.

Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.

Department of Molecular Biology & Genetics, Cornell University, Ithaca, New York, USA.

Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.

Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.

Department of Molecular Biology & Genetics, Cornell University, Ithaca, New York, USA.

Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.

Division of Infectious Diseases, Weill Cornell Medicine, New York, New York, USA.

Pub Type(s)

Journal Article

Research Support, N.I.H., Extramural

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34731091

Citation

Marston, Jez L., et al. "SARS-CoV-2 Infection Mediates Differential Expression of Human Endogenous Retroviruses and Long Interspersed Nuclear Elements." JCI Insight, vol. 6, no. 24, 2021.

Marston JL, Greenig M, Singh M, et al. SARS-CoV-2 infection mediates differential expression of human endogenous retroviruses and long interspersed nuclear elements. JCI Insight. 2021;6(24).

Marston, J. L., Greenig, M., Singh, M., Bendall, M. L., Duarte, R. R. R., Feschotte, C., Iñiguez, L. P., & Nixon, D. F. (2021). SARS-CoV-2 infection mediates differential expression of human endogenous retroviruses and long interspersed nuclear elements. JCI Insight, 6(24). https://doi.org/10.1172/jci.insight.147170

Marston JL, et al. SARS-CoV-2 Infection Mediates Differential Expression of Human Endogenous Retroviruses and Long Interspersed Nuclear Elements. JCI Insight. 2021 12 22;6(24) PubMed PMID: 34731091.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - SARS-CoV-2 infection mediates differential expression of human endogenous retroviruses and long interspersed nuclear elements. AU - Marston,Jez L, AU - Greenig,Matthew, AU - Singh,Manvendra, AU - Bendall,Matthew L, AU - Duarte,Rodrigo R R, AU - Feschotte,Cédric, AU - Iñiguez,Luis P, AU - Nixon,Douglas F, Y1 - 2021/12/22/ PY - 2020/12/28/received PY - 2021/10/29/accepted PY - 2021/11/4/pubmed PY - 2022/1/7/medline PY - 2021/11/3/entrez KW - COVID-19 KW - Infectious disease KW - Innate immunity JF - JCI insight JO - JCI Insight VL - 6 IS - 24 N2 - SARS-CoV-2 promotes an imbalanced host response that 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 bioinformatics tool, Telescope, we showed that SARS-CoV-2 infection led to upregulation or downregulation of TE transcripts, a subset of which differed from cells infected with SARS, Middle East respiratory syndrome coronavirus (MERS-CoV or MERS), influenza A virus (IAV), respiratory syncytial virus (RSV), and human parainfluenza virus type 3 (HPIV3). 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 showed that TEs differentially expressed in SARS-CoV-2 infection were enriched for binding sites for transcription factors involved in immune responses and for pioneer transcription factors. In samples from patients with COVID-19, there was significant TE overexpression in bronchoalveolar lavage fluid and downregulation in PBMCs. Thus, although 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. SN - 2379-3708 UR - https://www.unboundmedicine.com/medline/citation/34731091/SARS_CoV_2_infection_mediates_differential_expression_of_human_endogenous_retroviruses_and_long_interspersed_nuclear_elements_ DB - PRIME DP - Unbound Medicine ER -