Small RNA Plays Important Roles in Virus–Host Interactions

Abstract

Non-coding small RNAs play important roles in virus–host interactions. For hosts, small RNAs can serve as sensors in antiviral pathways including RNAi and CRISPR; for viruses, small RNAs can be involved in viral transcription and replication. This paper covers several recent discoveries on small RNA mediated virus–host interactions, and focuses on influenza virus cap-snatching and a few important virus sensors including PIR-1, RIG-I like protein DRH-1 and piRNAs. The paper also discusses recent advances in mammalian antiviral RNAi.

How do the severe acute respiratory coronavirus 2 (SARS-CoV-2) and its variants escape the host protective immunity and mediate pathogenesis?

“…Thus the initial PAMP-PRR interaction Martin-Sancho et al ( 2021 ), van der Made et al ( 2020 ), Wan et al ( 2020 ) Avoidance of innate immunity during viral entry A defective interferon (IFN) response to SARS-CoV-2 by host that is resulted due to the impairment of expression of the IFN-stimulated genes (ISGs) encoding mainly LY6E , whose product stops the viral replication onward Martin-Sancho et al ( 2021 ), Kikkert ( 2020 ), Snijder et al ( 2020 ) Downregulation of several ISGs which specifically interferes the entry of SARS-CoV-2 spike (S) protein Suppression of IFN-1 induced anti-viral state triggers hyper-inflammation and COVID-19 severity Wan et al ( 2020 ), Snijder et al ( 2020 ) Defective endosomal factors which are actually directed to inhibit the entry of SARS-CoV-2 Loss of control to inhibit SARS-CoV-2 replication Loss of expression of the required RNA binding proteins which are supposed to hinder the viral RNA synthesis Martin-Sancho et al ( 2021 ), V'kovski et al ( 2021 ) Lack of production of the cluster of endoplasmic reticulum (ER)/Golgi-resident anti-viral ISGs which are dedicated to suppress the genes required for viral assembly Curved membrane vesicles Such modification of intracellular membranes makes the SARS-CoV-2 RNA replication easier Klein et al ( 2020 ) Cap-snatching process The host capping enzymes may be employed by SARS-CoV-2, resulting in viral mRNAs consisting of both the host capped small RNA (addition of a 7-methyl guanosine; and lacking of the 2′-O-methylation) and the virus-encoded RNA. Thus, the SARS-CoV-2 RNAs may escape recognition by the host innate immune RNA sensors Beyer and Forero ( 2022 ), Mandilara et al ( 2021 ), Kikkert ( 2020 ), Dai et al ( 2020 ) Avoidance of recognition by the melanoma differentiation-associated protein (MDA5) sensor Avoid recognition by the MDA5 sensor which controls the innate immune response to SARS-CoV-2 in ...…”

“…It’s interesting to note that in order to make viral proteins, most viruses have been reported to hijack the host translational machineries, i.e., the host capping enzymes and utilizing the capped host mRNAs as substrates (Dai et al 2020 ). The short, 5′-capped transcripts produced by the cellular DNA-dependent RNA polymerase II from the host mRNAs is the process that is known as the cap-snatching mechanism (Mandilara et al 2021 ; Kikkert 2020 ).…”

“…The short, 5′-capped transcripts produced by the cellular DNA-dependent RNA polymerase II from the host mRNAs is the process that is known as the capsnatching mechanism (Mandilara et al 2021;Kikkert 2020). Such cap-snatching process has been observed in several positive stranded RNA viruses and in the Influenza virus which possess the viral mRNAs comprising both the host capped small RNA (addition of a 7-methyl guanosine; and lacking of the 2′-O-methylation) and the virus-encoded RNA (Dai et al 2020;Drappier et al 2015). SARS-CoV-2 RNA may employ several mechanisms to avoid the host immune response for its undisturbed transcription and translation.…”

Nonstructural protein NS26 of grass carp reovirus is a principal regulator for viral replication and infection

“…RNA interference (RNAi) is a powerful tool for probing gene function (Dai & Gu, 2020; Zhang et al., 2018). Transient or stable knockdown of viral genes is one of the commonly used techniques in examining viral gene functions (Andino et al., 2015).…”