The Interplay Between Viral-Derived miRNAs and Host Immunity During Infection

Mishra, Richa; Kumar, Ashish; Ingle, Harshad; Kumar, Himanshu

doi:10.3389/fimmu.2019.03079

Cited by 143 publications

(158 citation statements)

References 186 publications

(175 reference statements)

Supporting

Mentioning

158

Contrasting

Order By: Relevance

“…Therefore, molecular elucidation of the roles of miRNAs in host-virus interaction might provide a deeper understanding for viral pathogenesis and the development of an effective antiviral therapy as shown in several viruses including Herpesvirus, Enterovirus and Hepatitis C (Piedade & Azevedo-Pereira, 2016;Engelmann et al, 2018;Khatun & Ray, 2019). Although the detailed knowledge about viral miRNAs have been obtained from DNA viruses, it is still controversial for RNA viruses that whether they produce their own miRNAs or not (Mishra et al, 2019). However, there are several reports showing the presence of non-canonical (due to the lack of classical stem-loop structure in miRNAs), small miRNA-like small RNAs produced during viral infections as shown in H5N1 Influenza (Li et al, 2018), Ebola virus (Liang et al, 2014) and HIV-1 (Klase et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection

Demirci

Adan

2020

PeerJ

165

145

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression found in more than 200 diverse organisms. Although it is still not fully established if RNA viruses could generate miRNAs, there are examples of miRNA like sequences from RNA viruses with regulatory functions. In the case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), there are several mechanisms that would make miRNAs impact the virus, like interfering with viral replication, translation and even modulating the host expression. In this study, we performed a machine learning based miRNA prediction analysis for the SARS-CoV-2 genome to identify miRNA-like hairpins and searched for potential miRNA-based interactions between the viral miRNAs and human genes and human miRNAs and viral genes. Overall, 950 hairpin structured sequences were extracted from the virus genome and based on the prediction results, 29 of them could be precursor miRNAs. Targeting analysis showed that 30 viral mature miRNA-like sequences could target 1,367 different human genes. PANTHER gene function analysis results indicated that viral derived miRNA candidates could target various human genes involved in crucial cellular processes including transcription, metabolism, defense system and several signaling pathways such as Wnt and EGFR signalings. Protein class-based grouping of targeted human genes showed that host transcription might be one of the main targets of the virus since 96 genes involved in transcriptional processes were potential targets of predicted viral miRNAs. For instance, basal transcription machinery elements including several components of human mediator complex (MED1, MED9, MED12L, MED19), basal transcription factors such as TAF4, TAF5, TAF7L and site-specific transcription factors such as STAT1 were found to be targeted. In addition, many known human miRNAs appeared to be able to target viral genes involved in viral life cycle such as S, M, N, E proteins and ORF1ab, ORF3a, ORF8, ORF7a and ORF10. Considering the fact that miRNA-based therapies have been paid attention, based on the findings of this study, comprehending mode of actions of miRNAs and their possible roles during SARS-CoV-2 infections could create new opportunities for the development and improvement of new therapeutics.

show abstract

Section: Discussionmentioning

confidence: 99%

Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection

Demirci

Adan

2020

PeerJ

165

145

View full text Add to dashboard Cite

show abstract

“…Although host microRNAs are either utilized or regulated by viruses, viral miRNAs are another side of the coin; they regulate host gene expression, cellular proliferation, stress-related genes, and even viral gene expression (Cullen, 2010 ; Haasnoot and Berkhout, 2011 ; Lai et al, 2014 ). A summary explored how a number of DNA and RNA viruses produce miRNAs known as viral miRNAs (v-miRNAs) to evade the host immune response (Mishra et al, 2020 ). Novel viral miRNAs have been predicted to play an important role in neurological disorders as well (Islam et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Regulator miRNA Pattern Differences Among SARS-CoV, SARS-CoV-2, and SARS-CoV-2 World-Wide Isolates Delineated the Mystery Behind the Epic Pathogenicity and Distinct Clinical Characteristics of Pandemic COVID-19

et al. 2020

View full text Add to dashboard Cite

A detailed understanding of the molecular mechanism of SARS-CoV-2 pathogenesis is still elusive, and there is a need to address its deadly nature and to design effective therapeutics. Here, we present a study that elucidates the interplay between the SARS-CoV and SARS-CoV-2 viruses' and host's miRNAs, an epigenetic regulator, as a mode of pathogenesis; and we explored how the SARS-CoV and SARS-CoV-2 infections differ in terms of their miRNA-mediated interactions with the host and the implications this has in terms of disease complexity. We have utilized computational approaches to predict potential host and viral miRNAs and their possible roles in different important functional pathways. We have identified several putative host antiviral miRNAs that can target the SARS viruses and also predicted SARS viruses-encoded miRNAs targeting host genes. In silico predicted targets were also integrated with SARS-infected human cell microarray and RNA-seq gene expression data. A comparison between the host miRNA binding profiles on 67 different SARS-CoV-2 genomes from 24 different countries with respective country's normalized death count surprisingly uncovered some miRNA clusters, which are associated with increased death rates. We have found that induced cellular miRNAs can be both a boon and a bane to the host immunity, as they have possible roles in neutralizing the viral threat; conversely, they can also function as proviral factors. On the other hand, from over representation analysis, our study revealed that although both SARS-CoV and SARS-CoV-2 viral miRNAs could target broad immunesignaling pathways; only some of the SARS-CoV-2 miRNAs are found to uniquely target some immune-signaling pathways, such as autophagy, IFN-I signaling, etc., which might Khan et al. miRNA Roles in SARS-CoV-2 Infection suggest their immune-escape mechanisms for prolonged latency inside some hosts without any symptoms of COVID-19. Furthermore, SARS-CoV-2 can modulate several important cellular pathways that might lead to the increased anomalies in patients with comorbidities like cardiovascular diseases, diabetes, breathing complications, etc. This might suggest that miRNAs can be a key epigenetic modulator behind the overcomplications amongst the COVID-19 patients. Our results support that miRNAs of host and SARS-CoV-2 can indeed play a role in the pathogenesis which can be further concluded with more experiments. These results will also be useful in designing RNA therapeutics to alleviate the complications from COVID-19.

show abstract

“…The first viral miRNAs were identified in 2004 in the Epstein-Barr virus (EBV) [75], whereas those encoded by HCMV were identified in 2005 [19]. Therapeutic strategies aimed at counteracting viral miRNA action, through the administration of antago-miRNAs (complementary single-stranded oligonucleotides), may represent an interesting approach to neutralize the viral infection [76]. Furthermore, targeting viral miRNAs instead of cellular ones may decrease the side effects on humans and solve the question of site-specific/non-toxic targeted release [77].…”

Section: Resultsmentioning

confidence: 99%

Impact of Natural Occurring ERAP1 Single Nucleotide Polymorphisms within miRNA-Binding Sites on HCMV Infection

D’Amico

Tempora

Lucarini

et al. 2020

IJMS

View full text Add to dashboard Cite

Human cytomegalovirus (HCMV) is a β-herpesvirus that causes serious problems in people with a compromised immune system, whereas it coexists asymptomatically within the host with a healthy immune system. Like other viruses, HCMV has adopted multiples strategies to manipulate the host’s immune responses. Among them, expression of viral microRNAs (miRNAs) is one of the most intriguing. HCMV miR-UL112-5p and miR-US4-1 have been found to contribute to immune evasion by targeting the endoplasmic reticulum aminopeptidase 1 (ERAP1), a highly polymorphic key component of antigen processing. The current incomplete picture on the interplay between viral miRNAs and host immunity implies the need to better characterize the host genetic determinants. Naturally occurring single nucleotide polymorphisms (SNPs) within the miRNA binding sites of target genes may affect miRNA–target interactions. In this review, we focus on the relevance of 3′ untranslated region (3′UTR) ERAP1 SNPs within miRNA binding sites in modulating miRNA–mRNA interactions and the possible consequent individual susceptibility to HCMV infection. Moreover, we performed an in silico analysis using different bioinformatic algorithms to predict ERAP1 variants with a putative powerful biological function. This evidence provides a basis to deepen the knowledge on how 3′UTR ERAP1 variants may alter the mechanism of action of HCMV miRNAs, in order to develop targeted antiviral therapies.

show abstract

The Interplay Between Viral-Derived miRNAs and Host Immunity During Infection

Cited by 143 publications

References 186 publications

Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection

Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection

Epigenetic Regulator miRNA Pattern Differences Among SARS-CoV, SARS-CoV-2, and SARS-CoV-2 World-Wide Isolates Delineated the Mystery Behind the Epic Pathogenicity and Distinct Clinical Characteristics of Pandemic COVID-19

Impact of Natural Occurring ERAP1 Single Nucleotide Polymorphisms within miRNA-Binding Sites on HCMV Infection

Contact Info

Product

Resources

About