Both MicroRNA-155 and Virus-Encoded MiR-155 Ortholog Regulate TLR3 Expression

Hu, Xuming; Ye, Jianqiang; Qin, Aijian; Zou, Haitao; Shao, Hongxia; Qian, Kun

doi:10.1371/journal.pone.0126012

Cited by 28 publications

(21 citation statements)

References 52 publications

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“…The demonstrated significant up-regulation of mir-155 in nonpolluted/poly(I:C)-treated cells seen here was consistent with previous studies (Hu et al 2015;Waugh et al 2018). Up-regulation of mir-155 during viral infections is regarded as beneficial due to an enhanced anti-viral immunity (Tili et al 2013;Mehta and Baltimore 2016).…”

Section: Responses To Rna Virus Analog (Poly(i:c))supporting

confidence: 92%

“…After 8 h, the CEF here were still able to induce NF-jB1 in response to GaHV-2infection. During later stages, a modulation of NF-jB1 signaling might be a cause for the general down-regulation observed after 12 hr, since GaHV-2 has been shown to be able to down-regulate TLR3 protein expression in CEF (by a targeting TLR3 via miR-M4; Hu et al [2015]).…”

Section: Responses To Infection With Gahv-2mentioning

confidence: 99%

See 1 more Smart Citation

Environmental pollutants modulate RNA and DNA virus-activated miRNA-155 expression and innate immune system responses: Insights into new immunomodulative mechanisms*

Badry

Jaspers

Waugh

2020

Journal of Immunotoxicology

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Many persistent organic pollutants, such as polychlorinated biphenyls (PCBs), have high immunomodulating potentials. Exposure to them, in combination with virus infections, has been shown to aggravate outcomes of the infection, leading to increased viral titers and host mortality. Expression of immune-related microRNA (miR) signaling pathways (by host and/or virus) have been shown to be important in determining these outcomes; there is some evidence to suggest pollutants can cause dysregulation of miRNAs. It was thus hypothesized here that modulation of miRNAs (and associated cytokine genes) by pollutants exerts negative effects during viral infections. To test this, an in vitro study on chicken embryo fibroblasts (CEF) exposed to a PCB mixture (Aroclor 1260) and then stimulated with a synthetic RNA virus (poly(I:C)) or infected with a lymphoma-causing DNA virus (Gallid Herpes Virus 2 [GaHV-2]) was conducted. Using quantitative real-time PCR, expression patterns for mir-155, pro-inflammatory TNFa and IL-8, transcription factor NF-jB1, and anti-inflammatory IL-4 were investigated 8, 12, and 18 h after virus activation. The study showed that Aroclor1260 modulated mir-155 expression, such that a down-regulation of mir-155 in poly(

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Section: Responses To Rna Virus Analog (Poly(i:c))supporting

confidence: 92%

Section: Responses To Infection With Gahv-2mentioning

confidence: 99%

Environmental pollutants modulate RNA and DNA virus-activated miRNA-155 expression and innate immune system responses: Insights into new immunomodulative mechanisms*

Badry

Jaspers

Waugh

2020

Journal of Immunotoxicology

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“…Both miR-155 and virus-encoded miR-155 orthologs regulate the expression of TLR3, a TLR family member that recognizes double-stranded RNA carried by some viruses such as retroviruses. Upon recognition, TLR3 induces INF production, which signals other cells to increase their antiviral defenses [ 97 ].…”

Section: Introductionmentioning

confidence: 99%

DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging

et al. 2015

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A major issue in aging research is how cellular phenomena affect aging at the systemic level. Emerging evidence suggests that DNA damage response (DDR) signaling is a key mechanism linking DNA damage accumulation, cell senescence, and organism aging. DDR activation in senescent cells promotes acquisition of a proinflammatory secretory phenotype (SASP), which in turn elicits DDR and SASP activation in neighboring cells, thereby creating a proinflammatory environment extending at the local and eventually the systemic level. DDR activation is triggered by genomic lesions as well as emerging bacterial and viral metagenomes. Therefore, the buildup of cells with an activated DDR probably fuels inflamm-aging and predisposes to the development of the major age-related diseases (ARDs). Micro (mi)-RNAs - non-coding RNAs involved in gene expression modulation - are released locally and systemically by a variety of shuttles (exosomes, lipoproteins, proteins) that likely affect the efficiency of their biological effects. Here we suggest that some miRNAs, previously found to be associated with inflammation and senescence - miR-146, miR-155, and miR-21 - play a central role in the interplay among DDR, cell senescence and inflamm-aging. The identification of the functions of shuttled senescence-associated miRNAs is expected to shed light on the aging process and on how to delay ARD development.

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“…Additionally, SD patients showed an enrichment of genes associated with type 1 diabetes compared with CR patients (Supplemental Figure 2C, P = 0.035). miR-155 is known to be induced by TLR3 agonists such as Poly-IC (19,20), suggesting that responsiveness to the adjuvant may be important for clinical responses. Additionally, miR-155 is known to be required for effector CD8 + T cell responses in cancer (21).…”

Section: Resultsmentioning

confidence: 99%

Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas

Müller

Agnihotri²,

Shoger³

et al. 2018

JCI Insight

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Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine, which elicited consistent antigen-specific T cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD), partial response (PR), and near-complete/complete response (CR) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA sequencing on PBMC samples collected at multiple time points. Patients who showed CR demonstrated elevated levels of T cell activation markers, accompanied by a cytotoxic T cell response shortly after treatment initiation. At week 34, patients with CR demonstrated both IFN signaling and Poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T cell activation markers were associated with prolonged progression-free survival. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing phase II LGG vaccine immunotherapy, should monitor these response patterns.

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Both MicroRNA-155 and Virus-Encoded MiR-155 Ortholog Regulate TLR3 Expression

Cited by 28 publications

References 52 publications

Environmental pollutants modulate RNA and DNA virus-activated miRNA-155 expression and innate immune system responses: Insights into new immunomodulative mechanisms*

Environmental pollutants modulate RNA and DNA virus-activated miRNA-155 expression and innate immune system responses: Insights into new immunomodulative mechanisms*

DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging

Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas

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