MicroRNA and Nonsense Transcripts as Putative Viral Evasion Mechanisms

Abstract

Viral proteins encode numerous antiviral activities to modify the host immunity. In this article, we hypothesize that viral genomes and gene transcripts interfere with host gene expression using passive mechanisms to deregulate host microRNA (miRNA) activity. We postulate that various RNA viruses mimic or block binding between a host miRNA and its target transcript, a phenomenon mediated by the miRNA seed site at the 5′ end of miRNA. Virus-encoded miRNA seed sponges (vSSs) can potentially bind to host miRNA seed sites and prevent interaction with their native targets thereby relieving native miRNA suppression. In contrast, virus-encoded miRNA seed mimics (vSMs) may mediate considerable downregulation of host miRNA activity. We analyzed genomes from diverse RNA viruses for vSS and vSM signatures and found an abundance of these motifs indicating that this may be a mechanism of deceiving host immunity. Employing respiratory syncytial virus and measles virus as models, we reveal that regions surrounding vSS or vSM motifs have features characteristics of pre-miRNA templates and show that RSV viral transcripts are processed into small RNAs that may behave as vSS or vSM effectors. These data suggest that complex molecular interactions likely occur at the host-virus interface. Identifying the mechanisms in the network of interactions between the host and viral transcripts can help uncover ways to improve vaccine efficacy, therapeutics, and potentially mitigate the adverse events that may be associated with some vaccines.

Identification of Novel Hypothalamic MicroRNAs as Promising Therapeutics for SARS-CoV-2 by Regulating ACE2 and TMPRSS2 Expression: An In Silico Analysis

“…The rest of the transcripts are demarcated as noncoding RNAs, including microRNAs, which typically function post-transcriptionally to control the gene expression [ 69 ]. Various RNA viruses mimic or block the binding between a host miRNA and its target transcript, a phenomenon mediated by the miRNA seed site at the 5′ end of miRNA [ 70 ]. In past days, respiratory viral infections caused by influenza, rhinovirus, adenovirus, RSV, and coronaviruses can be related to aberrant host miRNA expression, and their effect on the host can results in cell apoptosis, inhibition of immunologic pathways, and downregulation of host antiviral responses [ 21 ].…”

Global mRNA and miRNA Analysis Reveal Key Processes in the Initial Response to Infection with WSSV in the Pacific Whiteleg Shrimp

“…Several studies have reported that the structure of viral miRNAs is similar to animal miRNAs due to the reliance on host enzymatic machinery for their production [121][122][123]. However, if their structures differ at all, for example as a result of non-canonical biogenesis pathways, this may lead to an absence of specific sequence features, such as 3 overhangs that sequencing adapters recognise and bind to during the library preparation protocols and within prediction software.…”

microRNA 1307 Is a Potential Target for SARS-CoV-2 Infection: An in Vitro Model

“… 11 , 12 According to recent reports, viral RNA may form complexes with host mRNAs and behave as miRs or rRNAs. 13 , 14 Evidence also supports that the miR biogenesis by host cells may provide an efficient antiviral response. 15 Several miRs have been identified as being differentially regulated in disease conditions and significantly correlate with elevated cytokine storms.…”

“…There are three main proposed mechanisms: the first option is that RNA-based viral genomes may either avoid being targeted by the cellular miRs expressed against virus infection or block the cellular miRs to regulate essential proteins in the main signaling pathways. , The second option is that viruses could synthesize their viral miRs to create a more favorable cellular environment to survive in the host cells . Third, viruses might manipulate cellular miRs to their advantage. , According to recent reports, viral RNA may form complexes with host mRNAs and behave as miRs or rRNAs. , Evidence also supports that the miR biogenesis by host cells may provide an efficient antiviral response . Several miRs have been identified as being differentially regulated in disease conditions and significantly correlate with elevated cytokine storms .…”