ABSTRACT
It is well-known that RNA is the target of numerous chemical modifications which currently amount to over a hundred. Among them, 5-methylcytosine (m5C) is a prevalent RNA modification in multiple eukaryotic RNA species, such as messenger RNAs (mRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), vault RNAs (vtRNAs), long non-coding RNAs (lncRNAs) and enhancer RNAs (eRNAs). In recent years, several techniques for detecting m5C have been developed, including UPLC-MS/MS, m5C-MeRIP-seq, PA-m5C-seq, RNA-BisSeq and nanopore sequencing. The rapid development of these high-throughput techniques sharply facilitates the in-depth studies of the biological functions of m5C. The m5C modification is enriched around start codon along mRNAs and conserved in tRNAs and rRNAs. It is a reversible RNA modification catalyzed by methyltransferases (NSUN, DNMT, and TRDMT family members) and removed by demethylases (TET family members and ALKBH1). The m5C modification can be recognized by a set of RNA-binding proteins (YBX family members, ALYREF and FMRP) and is widely involved in the regulation of RNA metabolic processes, including nuclear export, stability and translation. In addition, the dysregulation of m5C modification is closely related with the defect of DNA repair, cell proliferation, embryonic development and stem cell differentiation. Viruses are infectious agents that rely on host cells for replication. They have evolved numerous strategies to shape the cellular biosynthesis and metabolism machinery of hosts to complete their life cycle and propagate. One strategy is to modify viral RNAs using host m5C RNA methyltransferases (NSUN1, NSUN2, NSUN5 and DNMT2), and thus directly regulates their transcription, splicing and translation. So far, combined with the high-throughput techniques, some viral m5C landscapes have been precisely depicted, including human immunodeficiency virus type (HIV-1), murine leukemia virus (MLV), Epstein-Barr virus (EBV), and so on. Studies showed that the m5C level of retroviral mRNAs is much higher than cellular mRNAs, suggesting this modification can be a special marker for host cells to distinguish “self” and “non-self”. In addition, the m5C methylome of cellular RNAs is dynamically regulated under viral infection, leading to the suppression of host innate immunity. Therefore, it will be of great significance in the design and development of novel antiviral drugs by systemically understanding the molecular mechanisms of m5C modification in controlling viral replication and host innate immunity. In this review, the latest findings of m5C methyltransferases, demethylases, reader proteins and high-throughput sequencing techniques are presented. We discuss how m5C modification is catalyzed and recognized on viral RNAs of retrovirus, DNA virus, flavivirus and coronavirus. Furthermore, we summarize the roles of RNA m5C modification in viral replications and host innate immunity. This review will provide some valuable information for understanding the epigenetics in viral RNAs. © 2022 Chinese Academy of Sciences. All rights reserved.
ABSTRACT
Background: Although several key molecules have been identified to modulate SARS-CoV-2 invasion of human host cells, the molecules correlated with outcomes in COVID-19 caused by SARS-CoV-2 infection remain insufficiently explored. Methods: This study analyzed three RNA-Seq gene expression profiling datasets for COVID-19 and identified differentially expressed genes (DEGs) between COVID-19 patients and normal people, commonly in the three datasets. Furthermore, this study explored the correlation between the expression of these genes and clinical features in COVID-19 patients. Results: This analysis identified 13 genes significantly upregulated in COVID-19 patients' leukocyte and SARS-CoV-2-infected nasopharyngeal tissue compared to normal tissue. These genes included OAS1, OAS2, OAS3, OASL, HERC6, SERPING1, IFI6, IFI44, IFI44L, CMPK2, RSAD2, EPSTI1, and CXCL10, all of which are involved in antiviral immune regulation. We found that these genes' downregulation was associated with worse clinical outcomes in COVID-19 patients, such as intensive care unit (ICU) admission, mechanical ventilatory support (MVS) requirement, elevated D-dimer levels, and increased viral loads. Furthermore, this analysis identified two COVID-19 clusters based on the expression profiles of the 13 genes, termed COV-C1 and COV-C2. Compared with COV-C1, COV-C2 more highly expressed the 13 genes, had stronger antiviral immune responses, were younger, and displayed more favorable clinical outcomes. Conclusions: A strong antiviral immune response is essential in reducing severity of COVID-19.
Subject(s)
COVID-19 , Transcriptome , Antiviral Agents , COVID-19/genetics , Gene Expression Profiling , Humans , SARS-CoV-2ABSTRACT
The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field.