Abstract

Recent high-throughput sequencing revealed that only 2% of the transcribed human genome codes for proteins, while the majority of transcriptional products are non-coding RNAs (ncRNAs). Herein, we review the current knowledge regarding ncRNAs, both host- and virus-derived, and their role in respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections. RSV is known as the most common cause of lower respiratory tract infection (LRTI) in children, while hMPV is also a significant contributor to LRTI in the pediatrics population. Although RSV and hMPV are close members, belonging to the Pneumoviridae family, they induce distinct changes in the ncRNA profile. Several types of host ncRNAs, including long ncRNA (lncRNA), microRNAs (miRNAs), and transfer RNA (tRNA)-derived RNA fragments (tRFs), are involved as playing roles in RSV and/or hMPV infection. Given the importance of ncRNAs in regulating the expression and functions of genes and proteins, comprehensively understanding the roles of ncRNAs in RSV/hMPV infection could shed light upon the disease mechanisms of RSV and hMPV, potentially providing insights into the development of prevention strategies and antiviral therapy. The presence of viral-derived RNAs and the potential of using ncRNAs as diagnostic biomarkers are also discussed in this review.

Highlights

  • Respiratory syncytial virus (RSV) is the most common viral pathogen causing lower respiratory tract infection (LRTI) in young children, the elderly, and immune-compromised patients

  • MicroRNAs, Piwi-interacting RNAs, small nucleolar RNAs, and recently discovered transfer RNA (tRNA)-derived RNA fragments all belong to sncRNAs

  • We provide an overview of the latest knowledge and summarize existing data on ncRNAs involved in RSV and human metapneumovirus (hMPV) infections

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Summary

Introduction

Respiratory syncytial virus (RSV) is the most common viral pathogen causing lower respiratory tract infection (LRTI) in young children, the elderly, and immune-compromised patients. Clinical studies indicate that hMPV infection is linked to wheezing and asthma exacerbations in children and adults [12,13,14,15]. In the last two decades, extensive studies have provided numerous evidence for the involvement of ncRNAs in virtually all biological pathways [29,30], including proliferation, differentiation, apoptosis, autophagy, tissue repair and remodeling, and immune responses. MicroRNAs (miRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and recently discovered tRNA-derived RNA fragments (tRFs) all belong to sncRNAs. The infection of RSV or hMPV can significantly alter the expression profile of host ncRNAs and some impacted ncRNAs have been shown to play significant roles in viral replication and/or host responses. 2. miRNAs in RSV and hMPV Infections miRNAs, the most widely studied sncRNAs, are endogenous, single-stranded ncRNAs of. Approximately 60% of protein-coding genes in the human genome are more or less controlled by miRNAs, and the altered expression of miRNAs has been observed in various diseases, such as cancer, cardiac pathologies, airway diseases, and viral infections [36,37,38,39]

Both RSV and hMPV Alter Global miRNAs Expression Profile
Antiviral and Host Responses Controlled by miRNAs
Schematic
RSV Alters Exosomal piRNAs
Virus-Encoded sncRNAs
Can ncRNAs Serve as Targets for Antiviral Therapeutics?
Findings
Conclusions
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