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.
Highlights
SARS-CoV-2 infection has caused a worldwide pandemic with many millions of people infected
We assessed differential expression of retroelements, as well as genes, and compared retrotranscriptomic changes from SARS-CoV-2 infection with those induced by related pathogenic human coronaviruses, SARS and MERS, and by other common respiratory viruses, influenza A virus (IAV), respiratory syncytial virus (RSV), and human parainfluenza virus type 3 (HPIV3)
As described in Blanco-Melo et al (17), A549 cells were found to be relatively nonpermissive to SARS-CoV-2 infection in contrast to Calu-3 cells given their lower expression of the SARS-CoV-2 host receptor ACE2
Summary
SARS-CoV-2 infection has caused a worldwide pandemic with many millions of people infected. The development and distribution of SARS-CoV-2–specific vaccines have helped to suppress new infections, but a rising number of variant strains threaten global efforts to achieve sufficient protective immunity. Current studies have identified viral replication at the beginning of infection and a latter exuberant host immune response as 2 major opportunities for clinical intervention (1). Coronaviruses, including SARS-CoV-2, hijack host cellular machinery and gene expression networks in order to enhance their own replication within the cell (2, 3). During this process, viral genetic material and proteins serve as signals to elicit innate and adaptive immune responses (4–7). A recent study has recognized the co-option of a transposable element (TE) sequence for differential isoform usage in the expression of the ACE2 receptor in the response to SARS-CoV-2 infection (8), most coronavirus studies to date have ignored the potential contribution of TEs in disease pathogenesis
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
