Promotion of Hendra Virus Replication by MicroRNA 146a

Stewart, Cameron R.; Marsh, Glenn A.; Jenkins, Kristie A.; Gantier, Michael P.; Tizard, Mark; Middleton, Deborah; Lowenthal, John W.; Haining, Jessica; Izzard, Leonard; Gough, Tamara J.; Deffrasnes, Céline; Stambas, John; Robinson, Rachel; Heine, Hans G.; Pallister, Jackie; Foord, Adam J.; Bean, Andrew G.D.; Wang, Lin‐Fa

doi:10.1128/jvi.01342-12

Cited by 56 publications

(54 citation statements)

References 52 publications

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“…Thus, miRNAs play an important role in regulating the cellular developmental processes and the immune response, that is, the miRNAs not only play important roles in cell differentiation (4,5), proliferation (6,7), metabolism (8,9), and apoptosis (10,11) but also play critical roles in the regulation of innate and adaptive immune responses (12,13). Thus, it is not surprising that many viruses could alter the expression profile of host cellular miRNA to modulate innate and adaptive antiviral immunity and to facilitate viral replication or escape from host clearance (14)(15)(16)(17).…”

mentioning

confidence: 99%

MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction

Chen

Shi

Zhang

et al. 2017

J Virol

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MicroRNAs (miRNAs) play an important role in the regulation of immune responses. Previous studies have indicated that dysregulating the miRNAs leads to the immunosuppression of porcine reproductive and respiratory syndrome virus (PRRSV). However, it is not clear how PRRSV regulates the expression of host miRNA, which may lead to immune escape or promote the replication of the virus. The present work suggests that PRRSV upregulated the expression of miR-373 through elevating the expression of specificity protein 1 (Sp1) in MARC-145 cells. Furthermore, this work demonstrated that miR-373 promoted the replication of PRRSV, since miR-373 was a novel negative miRNA for the production of beta interferon (IFN-␤) by targeting nuclear factor IA (NFIA), NFIB, interleukin-1 receptor-associated kinase 1 (IRAK1), IRAK4, and interferon regulatory factor 1 (IRF1). We also found that both NFIA and NFIB were novel proteins for inducing the production of IFN-␤, and both of them could inhibit the replication of PRRSV. In conclusion, PRRSV upregulated the expression of miR-373 by elevating the expression of Sp1 and hijacked the host miR-373 to promote the replication of PRRSV by negatively regulating the production of IFN-␤.IMPORTANCE PRRSV causes one of the most economically devastating diseases of swine, and there is no effective method for controlling PRRSV. It is not clear how PRRSV inhibits the host's immune response and induces persistent infection. Previous studies have shown that PRRSV inhibited the production of type I IFN, and the treatment of type I IFN could efficiently inhibit the replication of PRRSV, so it will be helpful to design new methods of controlling PRRSV by understanding the molecular mechanism by which PRRSV modulated the production of IFN. The current work shows that miR-373, upregulated by PRRSV, promotes PRRSV replication, since miR-373 impaired the production of IFN-␤ by targeting NFIA, NFIB, IRAK1, IRAK4, and IRF1, and both NFIA and NFIB were antiviral proteins to PRRSV. In conclusion, this paper revealed a novel mechanism of PRRSV that impaired the production of type I IFN by upregulating miR-373 expression in MARC-145 cells.

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confidence: 99%

MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction

Chen

Shi

Zhang

et al. 2017

J Virol

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“…These miRNAs all share the same seed sequence (ACAUUC), implying significant congruency in function(s). The scale of the pro-viral impacts of miR-181 members is especially remarkable if we compare their effects to that of miR-146a (Fig 2A), which we previously validated as pro-viral for HeV [22]. In addition to miR-181, most members of the miR-17~93 family were pro-viral (Fig 2B).…”

Section: Resultsmentioning

confidence: 91%

Dual microRNA Screens Reveal That the Immune-Responsive miR-181 Promotes Henipavirus Entry and Cell-Cell Fusion

et al. 2016

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Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are bat-borne viruses that cause fatal disease in humans and a range of other mammalian species. Gaining a deeper understanding of host pathways exploited by henipaviruses for infection may identify targets for new anti-viral therapies. Here we have performed genome-wide high-throughput agonist and antagonist screens at biosafety level 4 to identify host-encoded microRNAs (miRNAs) impacting henipavirus infection in human cells. Members of the miR-181 and miR-17~93 families strongly promoted Hendra virus infection. miR-181 also promoted Nipah virus infection, but did not affect infection by paramyxoviruses from other genera, indicating specificity in the virus-host interaction. Infection promotion was primarily mediated via the ability of miR-181 to significantly enhance henipavirus-induced membrane fusion. Cell signalling receptors of ephrins, namely EphA5 and EphA7, were identified as novel negative regulators of henipavirus fusion. The expression of these receptors, as well as EphB4, were suppressed by miR-181 overexpression, suggesting that simultaneous inhibition of several Ephs by the miRNA contributes to enhanced infection and fusion. Immune-responsive miR-181 levels was also up-regulated in the biofluids of ferrets and horses infected with Hendra virus, suggesting that the host innate immune response may promote henipavirus spread and exacerbate disease severity. This study is the first genome-wide screen of miRNAs influencing infection by a clinically significant mononegavirus and nominates select miRNAs as targets for future anti-viral therapy development.

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“…On one hand, viruses are capable of altering host miRNA profiles to optimize the cellular environment for replication or contribute to cytopathogenesis. Hendra virus stimulates host miR-146a to enhance viral replication by targeting ring finger protein (RNF) 11 and increasing NF-κB activity [227]. HIV downregulates the miR-17-92 cluster to promote HIV transcriptional elongation by targeting PCAF [228].…”

Section: • • Mmps and Viral Myocarditismentioning

confidence: 99%

Coxsackievirus B3 Replication and Pathogenesis

et al. 2015

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Viruses such as coxsackievirus B3 (CVB3) are entirely host cell-dependent parasites. Indeed, they must cleverly exploit various compartments of host cells to complete their life cycle, and consequently launch disease. Evolution has equipped this pico-rna-virus, CVB3, to use different strategies, including CVB3-induced direct damage to host cells followed by a host inflammatory response to CVB3 infection, and cell death to super-additively promote target organ tissue injury, and dysfunction. In this update, the patho-stratagems of CVB3 are explored from molecular, and systems-level approaches. In summarizing recent developments in this field, we focus particularly on mechanisms by which CVB3 can harness different host cell processes including kinases, host cell-killing and cell-eating machineries, matrix metalloproteinases and miRNAs to promote disease.

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Promotion of Hendra Virus Replication by MicroRNA 146a

Cited by 56 publications

References 52 publications

MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction

MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction

Dual microRNA Screens Reveal That the Immune-Responsive miR-181 Promotes Henipavirus Entry and Cell-Cell Fusion

Coxsackievirus B3 Replication and Pathogenesis

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