miRNAs in Herpesvirus Infection: Powerful Regulators in Small Packages

Dass, Debashree; Dhotre, Kishore; Chakraborty, Muskan; Nath, Anushka; Banerjee, Anwesha; Bagchi, Parikshit; Mukherjee, Anupam

doi:10.3390/v15020429

Cited by 14 publications

(7 citation statements)

References 144 publications

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“…Human herpesviruses display a lot of encoded miRNAs that regulate the expression of their genes, host genes, or both. Currently, in miRNA databases, more than 140 miRNAs out of the about 200 total viral miRNAs identified encoded by alpha, beta, and gamma herpesviruses are deposited [ 14 , 43 ]. Especially for viral miRNAs encoded by RNA viruses, which are more recently discovered than those encoded by DNA viruses, it is possible that the databases used for viral miRNAs detection are not extremely up to date.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, antisense locked nucleic acid (LNA) inhibitors of some miRNAs are currently being studied for their efficacy in reducing HCV replication [ 6 ]. Several viruses, particularly members of the Herpesviridae family, encode their viral miRNAs [ 12 , 13 , 14 ]. Moreover, it is well known that HIV also encodes for viral miRNAs [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Human and Viral microRNA Expression in Acute and Chronic HIV Infections

Lazzari,

Rozera,

Gagliardini

et al. 2024

Viruses

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Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the pathogenetic events related to different phases of HIV disease. Next-generation sequencing (NGS) of miRNA libraries was performed, and the reads were used to analyze miRNA differential expression in the plasma with AHI and CHI. Functional analysis was then undertaken to investigate the biological processes characterizing the two phases of HIV infection. Except for hsa-miR-122-5p, which was found in 3.39% AHI vs. 0.18% CHI, the most represented human miRNAs were similarly represented in AHI and CHI. However, when considering the overall detected miRNAs in AHI and CHI, 15 displayed differential expression (FDR p < 0.05). Functional analysis identified 163 target mRNAs involved in promoting angiogenesis activation in AHI versus CHI through the action of hsa-miR10b-5p, hsa-miR1290, hsa-miR1-3p, and hsa-miR296-5p. The viral miRNAs detected, all belonging to herpesviruses, accounted for only 0.014% of total reads. The present data suggest that AHI patients exhibit strong innate immune activation through the upregulation of hsa-miR-122-5p and early activation of angiogenesis. More specific investigations are needed to study the role of viral miRNAs in HIV pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human and Viral microRNA Expression in Acute and Chronic HIV Infections

Lazzari,

Rozera,

Gagliardini

et al. 2024

Viruses

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“…The small RNA molecule, 24B_1, investigated in this work and originating from the Stx phage, deserves special attention in this context. While other microRNA-size, phage-encoded regulatory RNAs have not been described yet, similar molecules are well-documented in viruses that infect eukaryotic cells, particularly herpesviruses [ 44 , 45 ]. Notably, this sRNA shares several similarities with herpesviral microRNAs.…”

Section: Discussionmentioning

confidence: 99%

Bacteriophage-encoded 24B_1 molecule resembles herpesviral microRNAs and plays a crucial role in the development of both the virus and its host

Bloch,

Lewandowska,

Zwolenkiewicz

et al. 2023

PLoS ONE

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The 24B_1 small non-coding RNA molecule has been identified in Escherichia coli after induction of Shiga toxin-converting bacteriophage Φ24B. In this work, we focused on its direct role during phage and bacterial host development. We observed that in many aspects, this phage sRNA resembles herpesviral microRNAs. Similar to microRNAs, the mature 24B_1 is a short molecule, consisting of just 20 nucleotides. It is generated by cleaving the 80-nt long precursor transcript, and likely it undergoes a multi-step maturation process in which the Hfq protein plays an important role, as confirmed by demonstration of its binding to the 24B_1 precursor, but not to the 24B_1 mature form. Moreover, 24B_1 plays a significant role in maintaining the prophage state and reprogramming the host’s energy metabolism. We proved that overproduction of this molecule causes the opposite physiological effects to the mutant devoid of the 24B_1 gene, and thus, favors the lysogenic pathway. Furthermore, the 24B_1 overrepresentation significantly increases the efficiency of expression of phage genes coding for proteins CI, CII, and CIII which are engaged in the maintenance of the prophage. It seems that through binding to mRNA of the sdhB gene, coding for the succinate dehydrogenase subunit, the 24B_1 alters the central carbon metabolism and causes a drop in the ATP intracellular level. Interestingly, a similar effect, called the Warburg switch, is caused by herpesviral microRNAs and it is observed in cancer cells. The advantage of the Warburg effect is still unclear, however, it was proposed that the metabolism of cancer cells, and all rapidly dividing cells, is adopted to convert nutrients such as glucose and glutamine faster and more efficiently into biomass. The availability of essential building blocks, such as nucleotides, amino acids, and lipids, is crucial for effective cell proliferation which in turn is essential for the prophage and its host to stay in the lysogenic state.

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“…While there have been numerous reports on the regulation of HSV-1 infection by host miRNAs [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], the same cannot be said for HSV-2. Interestingly, the host miR-138 increases HSV-1 latency by targeting the host OCT-1 and FOXC1 genes as well as the viral ICP0 gene.…”

Section: Discussionmentioning

confidence: 99%

Combinatorial Effects of miRNAs in HSV-2 Infection of Macrophages: An In Silico and In Vitro Integration Approach

Banerjee,

Dass,

Dhotre

et al. 2023

Vaccines

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The rising issues of herpes simplex virus (HSV)-2 drug ramifications have encouraged the researchers to look for new and alternative approaches that pose minimum adversities in the host while efficiently reducing the HSV-2 infection. Although microRNAs (miRNAs), as unorthodox approaches, are gaining popularity due to eliciting highly reduced immunogenic reactions, their implications in HSV-2 research have been rarely explored. In this study, a pool of cellular miRNAs with significance in HSV-2-induced inflammatory and immune responses have been identified. Computationally recognizing the host targets of these miRNAs through network biology and machine learning, in vitro validation has been addressed along with the identification of their regulation in the HSV-2 infection. To signify the role of these identified miRNAs, they have been individually ectopically expressed in macrophages. The ectopic expression of the individual miRNAs was able to suppress HSV-2 viral gene expression. Taking a step forward, this study also highlights the Box–Behnken design-based combinatorial effect of ectopically expressed miRNAs on maximum suppression of HSV-2 infectivity. Therefore, the concentrations of each of the miRNAs optimized in a combination, predicted through expert systems biology tools were validated in vitro to not only recover the target expressions but also inhibit the HSV-2 infection in the macrophages. Overall, the study offers miRNAs as intriguing alternatives to commercially available medications against HSV-2. Moreover, the study illuminates the prophylactic potentiality of the miRNAs, which is significant since there are currently no vaccines available for HSV-2. Moving forward, the miRNAs are employed in an innovative strategy that incorporates intricate biological system models and in vitro confirmation methods to deliver a prospective combinatorial miRNA therapeutic against HSV-2 infection.

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miRNAs in Herpesvirus Infection: Powerful Regulators in Small Packages

Cited by 14 publications

References 144 publications

Human and Viral microRNA Expression in Acute and Chronic HIV Infections

Human and Viral microRNA Expression in Acute and Chronic HIV Infections

Bacteriophage-encoded 24B_1 molecule resembles herpesviral microRNAs and plays a crucial role in the development of both the virus and its host

Combinatorial Effects of miRNAs in HSV-2 Infection of Macrophages: An In Silico and In Vitro Integration Approach

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