SARS-CoV-2 infection mediates differential expression of human endogenous retroviruses and long interspersed nuclear elements

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.

Syncytin, envelope protein of human endogenous retrovirus (HERV): no longer ‘fossil’ in human genome

“…HERV-FRD is the most highly upregulated family among other HERVs. Another recent study supports the finding of upregulated HERVs in BALF of COVID-19 patients (Marston et al 2021 ). Both syncytin-1 and syncytin-2 are highly expressed in BALF of COVID-19 patients, but none are detected in PBMCs (Charvet et al 2021 ).…”

“…Although vaccination against SARS-CoV-2 helps protect from COVID-19, some people are hesitant to the vaccinations for a number of reasons, including a rumor that concerns a cross-activity of anti-SARS-CoV-2 spike protein syncytin-1 in the placenta. Also, some recent reports show the differentially expressed HERVs in COVID-19 patients, suggesting that HERVs may be involved in COVID-19 epidemiology (El-Shehawi et al 2020 ; Kitsou et al 2021 ; Marston et al 2021 ). On the other hand, it has been reported that CRP level increases in serum from COVID-19 patients and positively correlates with disease severity (Chen et al 2020 ; Luo et al 2020 ).…”

Impaired activation of Transposable Elements in SARS-CoV-2 infection

“…Although some studies have addressed TEs expression following SARS-CoV-2 infection 27,28 , none has considered the cell type and basal TE expression levels as important characteristics of their analysis.…”

“…Although some studies have addressed TEs expression following SARS-CoV-2 infection 27,28 , none has considered the cell type and basal TE expression levels as important characteristics of their analysis. Here, we suggest that SARS-CoV-2 infected cells that fail to activate an immediate and effective TE response will be more likely to demonstrate a late immune response.…”

Role Of Retroelements In The Development Of COVID-19 Neurological Consequences

“…Based on the analysis of ChIP-Seq data, SARS-CoV-2 promotes the expression of certain Res that are involved in the transcriptional regulation of immune response genes. The experiment conducted on human cell lines demonstrated that SARS-CoV-2 infection resulted in increased levels of 52 different HERV and 40 LINE1 REs [30]. The transcriptome of bronchoalveolar lavage and peripheral blood monocytes obtained from COVID-19 patients was also characterized by a significant increase in the level of HERV transcripts, compared with healthy individuals [31].…”