Identification and characterization of endogenous retroviruses upon SARS-CoV-2 infection
Endogenous retroviruses (ERVs) derived from the long terminal repeat (LTR) family of transposons constitute a significant portion of the mammalian genome, with origins tracing back to ancient viral infections. Despite comprising approximately 8% of the human genome, the specific role of ERVs in the...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1294020/full |
| _version_ | 1827292655987458048 |
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| author | Xuefei Guo Yang Zhao Fuping You |
| author_facet | Xuefei Guo Yang Zhao Fuping You |
| author_sort | Xuefei Guo |
| collection | DOAJ |
| description | Endogenous retroviruses (ERVs) derived from the long terminal repeat (LTR) family of transposons constitute a significant portion of the mammalian genome, with origins tracing back to ancient viral infections. Despite comprising approximately 8% of the human genome, the specific role of ERVs in the pathogenesis of COVID-19 remains unclear. In this study, we conducted a genome-wide identification of ERVs in human peripheral blood mononuclear cells (hPBMCs) and primary lung epithelial cells from monkeys and mice, both infected and uninfected with SARS-CoV-2. We identified 405, 283, and 206 significantly up-regulated transposable elements (TEs) in hPBMCs, monkeys, and mice, respectively. This included 254, 119, 68, and 28 ERVs found in hPBMCs from severe and mild COVID-19 patients, monkeys, and transgenic mice expressing the human ACE2 receptor (hACE2) and infected with SARS-CoV-2. Furthermore, analysis using the Genomic Regions Enrichment of Annotations Tool (GREAT) revealed certain parental genomic sequences of these up-regulated ERVs in COVID-19 patients may be involved in various biological processes, including histone modification and viral replication. Of particular interest, we identified 210 ERVs specifically up-regulated in the severe COVID-19 group. The genes associated with these differentially expressed ERVs were enriched in processes such as immune response activation and histone modification. HERV1_I-int: ERV1:LTR and LTR7Y: ERV1:LTR were highlighted as potential biomarkers for evaluating the severity of COVID-19. Additionally, validation of our findings using RT-qPCR in Bone Marrow-Derived Macrophages (BMDMs) from mice infected by HSV-1 and VSV provided further support to our results. This study offers insights into the expression patterns and potential roles of ERVs following viral infection, providing a valuable resource for future studies on ERVs and their interaction with SARS-CoV-2. |
| first_indexed | 2024-04-24T13:09:35Z |
| format | Article |
| id | doaj.art-6629bff23922481a8e174d03b30f79cb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T13:09:35Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6629bff23922481a8e174d03b30f79cb2024-04-05T04:56:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-04-011510.3389/fimmu.2024.12940201294020Identification and characterization of endogenous retroviruses upon SARS-CoV-2 infectionXuefei GuoYang ZhaoFuping YouEndogenous retroviruses (ERVs) derived from the long terminal repeat (LTR) family of transposons constitute a significant portion of the mammalian genome, with origins tracing back to ancient viral infections. Despite comprising approximately 8% of the human genome, the specific role of ERVs in the pathogenesis of COVID-19 remains unclear. In this study, we conducted a genome-wide identification of ERVs in human peripheral blood mononuclear cells (hPBMCs) and primary lung epithelial cells from monkeys and mice, both infected and uninfected with SARS-CoV-2. We identified 405, 283, and 206 significantly up-regulated transposable elements (TEs) in hPBMCs, monkeys, and mice, respectively. This included 254, 119, 68, and 28 ERVs found in hPBMCs from severe and mild COVID-19 patients, monkeys, and transgenic mice expressing the human ACE2 receptor (hACE2) and infected with SARS-CoV-2. Furthermore, analysis using the Genomic Regions Enrichment of Annotations Tool (GREAT) revealed certain parental genomic sequences of these up-regulated ERVs in COVID-19 patients may be involved in various biological processes, including histone modification and viral replication. Of particular interest, we identified 210 ERVs specifically up-regulated in the severe COVID-19 group. The genes associated with these differentially expressed ERVs were enriched in processes such as immune response activation and histone modification. HERV1_I-int: ERV1:LTR and LTR7Y: ERV1:LTR were highlighted as potential biomarkers for evaluating the severity of COVID-19. Additionally, validation of our findings using RT-qPCR in Bone Marrow-Derived Macrophages (BMDMs) from mice infected by HSV-1 and VSV provided further support to our results. This study offers insights into the expression patterns and potential roles of ERVs following viral infection, providing a valuable resource for future studies on ERVs and their interaction with SARS-CoV-2.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1294020/fullCOVID-19SARS-CoV-2TEsERVsErv1RNA-Seq |
| spellingShingle | Xuefei Guo Yang Zhao Fuping You Identification and characterization of endogenous retroviruses upon SARS-CoV-2 infection Frontiers in Immunology COVID-19 SARS-CoV-2 TEs ERVs Erv1 RNA-Seq |
| title | Identification and characterization of endogenous retroviruses upon SARS-CoV-2 infection |
| title_full | Identification and characterization of endogenous retroviruses upon SARS-CoV-2 infection |
| title_fullStr | Identification and characterization of endogenous retroviruses upon SARS-CoV-2 infection |
| title_full_unstemmed | Identification and characterization of endogenous retroviruses upon SARS-CoV-2 infection |
| title_short | Identification and characterization of endogenous retroviruses upon SARS-CoV-2 infection |
| title_sort | identification and characterization of endogenous retroviruses upon sars cov 2 infection |
| topic | COVID-19 SARS-CoV-2 TEs ERVs Erv1 RNA-Seq |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1294020/full |
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