Decoding the ncRNA Script: Elucidation of Major Host Regulatory lncRNAs and circRNAs Shaping RNA Virus Pathogenesis

Viruses are key infectious agents causing large-scale mortality among humans every year with the recent example of the devastating COVID-19 pandemic. RNA viruses are often associated with higher pathogenicity and their molecular mechanisms of entry into host cells, replication, transmission, and propagation remain poorly understood. To facilitate virus replication and propagation, these viruses regulate the host gene transcription and translation, key cellular processes like apoptosis, autophagy, innate as well as adaptive immune responses, lipid biosynthesis, and other key host signaling processes. They hijack and exploit the host cell machinery by modulating the expression of host proteins and ncRNAs. Some of the regulatory RNAs that these viruses modulate involve lncRNAs, circRNAs and ceRNA networks. RNA viruses alter or control key cellular processes of these RNAs by directly or indirectly interacting with both host and viral proteins and other non-coding RNAs. Through the alteration of regulation of non-coding RNAs, the viruses have been demonstrated to alter several biological processes primarily metabolic pathways, inflammation, and immune pathways like interferon signaling and other innate immune pathways to aid virus replication, pathogenesis and immune evasion. These differentially expressed regulatory RNAs can be further studied to develop potential antiviral therapeutics and vaccines. CeRNA networks involve the role of protein-coding mRNAs and competing ncRNAs like lncRNA, miRNA, and circRNA. This review explores some of the reported modulations of host lncRNAs, circRNAs, and ceRNA networks in RNA virus infections to understand their importance and role in virus pathogenesis.