Perversely Expressed Long Noncoding Rnas Can Alter Host Response and Viral Proliferation in SARS-CoV-2 Infection

Abstract

Background: Regulatory roles of long noncoding RNAs (lncRNAs) during viral infection has become more evident in last decade, but are yet to be explored for SARS-CoV-2. Materials & methods: We analyzed RNA-seq dataset of SARS-CoV-2 infected lung epithelial cells to identify differentially expressed genes. Results: Our analyses uncover 21 differentially expressed lncRNAs broadly involved in cell survival and regulation of gene expression. These lncRNAs can directly interact with six differentially expressed protein-coding genes, and ten host genes that interact with SARS-CoV-2 proteins. Also, they can block the suppressive effect of nine microRNAs induced in viral infections. Conclusion: Our investigation determines that deregulated lncRNAs in SARS-CoV-2 infection are involved in viral proliferation, cellular survival, and immune response, ultimately determining disease outcome.

Functional and tissue enrichment analyses suggest that SARS-CoV-2 infection affects host metabolism and catabolism mediated by interference on host proteins

“…Regulation of catabolism of nucleic acids and their metabolites can contribute to viral pathogenesis [ 28 ]. For instance, SARS-CoV-2 nsp8 appears to reduce the catabolism capacity of the host exosome complex against viral mRNAs [ 29 ]. In addition, components of exosome complex (EXOSC2, EXOSC3, EXOSC5, and EXOSC8) included in the set of SARS-CoV-2-associated host proteins presented highlighted function involving nucleic acid catabolism processes (supplementary table 2 ).…”

Distinct Mucoinflammatory Phenotype and the Immunomodulatory Long Noncoding Transcripts Associated with SARS-CoV-2 Airway Infection

“…In addition to mucoinflammatory factor encoding mRNAs, another type of RNA, lncRNAs, have now been found to play vital roles in regulating the innate immune responses (12,13) and recent studies have shown that specific lncRNAs are differentially expressed during hostpathogen interactions following viral infection (18,19,34,35). That said, our group identified two novel epithelial lncRNAs, LASI (lncRNA on antisense strand to ICAM-1) and TOSL (TNFAIP3opposite strand lncRNA) that are differentially expressed during the mucus hypersecretory response (36) and blocking these lncRNA expression alleviates the mucin hyperexpression.…”

Noncoding RNA therapeutics — challenges and potential solutions

“… 340 ), which was previously shown to promote inflammatory injury in lung tissue via negative regulation of IL-8 (ref. 343 ), and of MIR3142HG 344 , 345 , which is also induced by pro-inflammatory IL-1β and positively regulates secretion of IL-8 and CCL2 (neutrophil/monocyte chemoattractant) in lung fibroblasts 346 . The complex interactions between host and viral noncoding genes in SARS-CoV-2 infection is thus only starting to be explored, but the findings so far hint at diverse opportunities to target COVID-19 disease with RNA-based therapeutics.…”