Role of miRNAs in regulating virus replication

Pandita, Sakshi; Verma, Assim; Kumar, Naveen

doi:10.1016/j.angen.2023.200162

Cited by 3 publications

(1 citation statement)

References 218 publications

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“…miRNAs are a class of approximately 22-nucleotide long non-coding RNAs [ 12 ] that can influence gene expression [ 13 ]. miRNAs have been shown to regulate various physiological and pathological processes such as cell proliferation and differentiation, development, angiogenesis, inflammation, cancer, and apoptosis [ 13–21 ]. miRNAs have also emerged as crucial regulators of the innate and adaptive immune responses [ 22–26 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of miR-29a as a novel biomarker for lumpy skin disease virus exposure in cattle

Kumar,

Kamboj,

Dhanda

et al. 2024

Virulence

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Micro RNAs (miRNAs) have been implicated in the regulation of maturation, proliferation, differentiation, and activation of immune cells. In this study, we demonstrated that miR-29a antagonizes IFN-γ production at early times post-LSDV infection in cattle. miR-29a was predicted to target upstream IFN-γ regulators, and its inhibition resulted in enhanced IFN-γ production in sensitized peripheral blood mononuclear cells (PBMCs). Further, stimulation of PBMCs with LSDV antigen exhibited lower levels of miR-29a, concomitant with a potent cell-mediated immune response (CMI), characterized by an increase in LSDV-specific CD8+ T cell counts and enhanced levels of IFN-γ, which eventually facilitated virus clearance. In addition, a few immunocompromised cattle (developed secondary LSDV infection at ~ 6 months) that failed to mount a potent cell-mediated immune response, were shown to maintain higher miR-29a levels. Furthermore, as compared to the sensitized crossbred cattle, PBMCs from sensitized Rathi (a native Indian breed) animals exhibited lower levels of miR-29a along with an increase in CD8+ T cell counts and enhanced levels of IFN-γ. Finally, we analysed that a ≥ 60% decrease in miR-29a expression levels in the PBMCs of sensitized cattle correlated with a potent CMI response. In conclusion, miR-29a expression is involved in antagonizing the IFN-γ response in LSDV-infected cattle and may serve as a novel biomarker for the acute phase of LSDV infection, as well as predicting the functionality of T cells in sensitized cattle. In addition, Rathi cattle mount a more potent CMI response against LSDV than crossbred cattle.

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Section: Introductionmentioning

confidence: 99%

Identification of miR-29a as a novel biomarker for lumpy skin disease virus exposure in cattle

Kumar,

Kamboj,

Dhanda

et al. 2024

Virulence

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Human cytomegalovirus microRNAs: strategies for immune evasion and viral latency

Sabbaghian,

Gheitasi,

Fadaee

et al. 2024

Arch Virol

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miR-191-5p suppresses PRRSV replication by targeting porcine EGFR to enhance interferon signaling

Pan,

Zhang,

et al. 2024

Front. Microbiol.

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Porcine reproductive and respiratory syndrome virus (PRRSV) is a major thread to the global swine industry, lack of effective control strategies. This study explores the regulatory role of a small non-coding RNA, miR-191-5p, in PRRSV infection. We observed that miR-191-5p significantly inhibits PRRSV in porcine alveolar macrophages (PAMs), contrasting with negligible effects in MARC-145 and HEK293-CD163 cells, suggesting a cell-specific antiviral effect. Further investigation unveiled that miR-191-5p directly targets the porcine epidermal growth factor receptor (EGFR), whose overexpression or EGF-induced activation suppresses type I interferon (IFN-I) signaling, promoting PRRSV replication. In contrast, siRNA-or miR-191-5p-induced EGFR downregulation or EGFR inhibitor boosts IFN-I signaling, reducing viral replication. Notably, this miRNA alleviates the suppressive effect of EGF on IFN-I signaling, underscoring its regulatory function. Further investigation revealed interconnections among miR-191-5p, EGFR and signal transducer and activator of transcription 3 (STAT3). Modulation of STAT3 activity influenced IFN-I signaling and PRRSV replication, with STAT3 knockdown countering EGFR activation-induced virus replication. Combination inhibition of STAT3 and miR-191-5p suggests that STAT3 acts downstream in EGFR’s antiviral response. Furthermore, miR-191-5p’s broad efficacy in restricting various PRRSV strains in PAMs was identified. Collectively, these findings elucidate a novel mechanism of miR-191-5p in activating host IFN-I signaling to inhibit PRRSV replication, highlighting its potential in therapeutic applications against PRRSV.

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Role of miRNAs in regulating virus replication

Cited by 3 publications

References 218 publications

Identification of miR-29a as a novel biomarker for lumpy skin disease virus exposure in cattle

Identification of miR-29a as a novel biomarker for lumpy skin disease virus exposure in cattle

Human cytomegalovirus microRNAs: strategies for immune evasion and viral latency

miR-191-5p suppresses PRRSV replication by targeting porcine EGFR to enhance interferon signaling

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