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Human Cytomegalovirus miR-UL112-3p Targets TLR2 and Modulates the TLR2/IRAK1/NFκB Signaling Pathway
Human cytomegalovirus (HCMV) is a herpesvirus that is a leading cause of congenital defects in newborns and can be deadly in people with weakened immunity. HCMV has developed multiple strategies to escape the host immune system. Among those, microRNAs (miRNAs) are short regulatory RNAs that target gene transcripts through sequence complementarity. HCMV expresses more than 20 miRNAs and several of them, in particular miR-UL112-3p, have been demonstrated to cooperate in evading the host antiviral immune response during infection. In this work we identified TLR2, a cell surface receptor that plays an important role in the detection and control of CMV infection, as a novel target of miR-UL112-3p. We demonstrate that miR-UL112-3p efficiently down-regulates endogenous TLR2 during infection, causing significant inhibition of the downstream signaling cascade. This work provides the first identified mechanism of TLR2 modulation by HCMV and is the first report of TLR2 targeting by a viral miRNA.
Vyšlo v časopise: Human Cytomegalovirus miR-UL112-3p Targets TLR2 and Modulates the TLR2/IRAK1/NFκB Signaling Pathway. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004881
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004881Souhrn
Human cytomegalovirus (HCMV) is a herpesvirus that is a leading cause of congenital defects in newborns and can be deadly in people with weakened immunity. HCMV has developed multiple strategies to escape the host immune system. Among those, microRNAs (miRNAs) are short regulatory RNAs that target gene transcripts through sequence complementarity. HCMV expresses more than 20 miRNAs and several of them, in particular miR-UL112-3p, have been demonstrated to cooperate in evading the host antiviral immune response during infection. In this work we identified TLR2, a cell surface receptor that plays an important role in the detection and control of CMV infection, as a novel target of miR-UL112-3p. We demonstrate that miR-UL112-3p efficiently down-regulates endogenous TLR2 during infection, causing significant inhibition of the downstream signaling cascade. This work provides the first identified mechanism of TLR2 modulation by HCMV and is the first report of TLR2 targeting by a viral miRNA.
Zdroje
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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium
Článek Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary TuberculosisČlánek Circumventing . Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic PlagueČlánek Admixture in Humans of Two Divergent Populations Associated with Different Macaque Host SpeciesČlánek Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR SelectionČlánek Selective Recruitment of Nuclear Factors to Productively Replicating Herpes Simplex Virus GenomesČlánek Fob1 and Fob2 Proteins Are Virulence Determinants of via Facilitating Iron Uptake from FerrioxamineČlánek Remembering MumpsČlánek Induces the Premature Death of Human Neutrophils through the Action of Its Lipopolysaccharide
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