Epistemic_Statements  

CORD-19:dd0159ba60fc4458dc4a2c632fe9072d8cc7ff36 JSONTXT 9 Projects

Annnotations TAB TSV DIC JSON TextAE-old TextAE

Id Subject Object Predicate Lexical cue
T1 1047-1246 Epistemic_statement denotes These results demonstrate the important role of miR-26a in modulating PRRSV infection and also support the possibility of using host miR-26a to achieve RNAi-mediated antiviral therapeutic strategies.
T2 2008-2237 Epistemic_statement denotes Host miRNAs can affect viral replication by binding directly to viral RNA (Lecellier et al., 2005) or by indirectly modulating host factors to provide a less permissive environment for virus replication (Triboulet et al., 2007) .
T3 2238-2383 Epistemic_statement denotes As miRNAs are small molecules without antigenic properties, they are considered to have potential efficacy in antiviral therapeutic applications.
T4 3254-3440 Epistemic_statement denotes Many strategies for controlling PRRSV transmission have been proposed but have generally shown little success, which has stimulated the search for new ways to control PRRSV transmission.
T5 3441-3534 Epistemic_statement denotes PRRSV can escape from innate immunity and cause persistent infections (Miller et al., 2004) .
T6 3665-3921 Epistemic_statement denotes Type I interferons can initiate the activation of JAK/STAT signaling to induce the expression of hundreds of IFN-stimulated genes (ISGs), which play an important role in antiviral activities (Albina et al., 1998; Katze et al., 2002; Overend et al., 2007) .
T7 3922-4032 Epistemic_statement denotes However, in contrast to porcine respiratory coronavirus, PRRSV is a poor IFN-inducer (Buddaert et al., 1998) .
T8 4414-4554 Epistemic_statement denotes Recent research has revealed that miR-23 may play a positive modulatory role in IFN production during PRRSV infection (Zhang et al., 2014) .
T9 5081-5244 Epistemic_statement denotes Our study reveals an example of a miRNA that affects viral propagation and highlights a host factor that may be important for future control measures against PRRS.
T10 13191-13601 Epistemic_statement denotes To screen potential miRNAs for their ability to inhibit PRRSV replication, mimics of 15 miRNAs that are well-conserved among different species and have been previously implicated in innate immunity and/or antiviral functions (Banerjee et al., 2013; Foley and O'Neill, 2012; Huang et al., 2014; Yoo and Liu, 2013; Pauley and Chan, 2008; Schulte et al., 2013; Selvamani et al., 2014) were synthesized (Table 1) .
T11 14016-14155 Epistemic_statement denotes 1B) , indicating that miR-26 has antiviral activity against PRRSV replication and that miR-26a is a more efficient suppressor than miR-26b.
T12 14424-14705 Epistemic_statement denotes To rule out the possibility that this antiviral effect of miR-26a was specific to an individual PRRSV strain, we analyzed the viral growth curves of two type 2 PRRSV strains (vJX143, vJXM100) and a type 1 PRRSV strain (vSHE) in MARC-145 cells transfected with NC or miR-26a mimics.
T13 15323-15534 Epistemic_statement denotes To exclude the possibility that reduced PRRSV replication was due to potential toxicity of the miR-26a mimic, MARC-145 cells were transfected with the miR-26a mimic at different doses (40 nM, 80 nM, and 160 nM).
T14 16047-16161 Epistemic_statement denotes As previously reported, miRNA-mRNA interactions may require seed-matched sites at nucleotides 2-8 (Bartel, 2009 ).
T15 17549-17623 Epistemic_statement denotes Notably, miR-26a was more efficient suppressing viral growth than miR-26b.
T16 17624-17735 Epistemic_statement denotes These results indicated that miR-26 family members, especially miR-26a, can inhibit vJX143 replication in PAMs.
T17 17916-18072 Epistemic_statement denotes Targeting a specific viral sequence represents an efficient strategy by which miRNAs can inhibit viral replication (Jopling, 2010; Lecellier et al., 2005) .
T18 18261-18654 Epistemic_statement denotes We determined whether miR-26a specifically targets the PRRSV genome to exert its antiviral effect by constructing a range of firefly luciferase reporter pGL3-Control based plasmids, which contained the cDNA fragments representing the 5 UTR, nsp1-nsp12, ORF2-ORF7, and the 3 UTR of the PRRSV genome Statistical significance was analyzed using t-tests; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
T19 19628-19770 Epistemic_statement denotes If the PRRSV cDNA insert contains a miR-26a target sequence, luciferase reporter expression is expected to be subjected to miR-26a-regulation.
T20 20215-20281 Epistemic_statement denotes Thus, miR-26a does not appear to target directly the PRRSV genome.
T21 22457-22618 Epistemic_statement denotes generated small RNA expression profiles at 12, 24 and 48 h post-infection to identify alterations in miRNA expression associated with PRRSV (Yoo and Liu, 2013) .
T22 22732-22803 Epistemic_statement denotes However, in this study, miR-26a was not mentioned (Yoo and Liu, 2013) .
T23 23088-23270 Epistemic_statement denotes However, PRRSV is a fast-evolving RNA virus (Prieto et al., 2009) and the relatively high mutation rate may limit the application of this kind of RNAi-mediated antiviral therapeutic.
T24 23271-23368 Epistemic_statement denotes Cellular miRNAs can also indirectly modulate cellular pathways that perturb the viral life cycle.
T25 23369-23579 Epistemic_statement denotes In particular, the activation or enhancement of innate antiviral immune pathways has been suggested to be responsible for the antiviral effect of certain miRNAs (Lecellier et al., 2005; Pedersen et al., 2007) .
T26 23580-23721 Epistemic_statement denotes In the current study, the reduction of PRRSV replication by miR-26a did not appear to involve direct targeting of the PRRSV genomic RNA (Fig.
T27 23900-24005 Epistemic_statement denotes These data led us to hypothesize that miR-26a might act on a cellular factor to reduce PRRSV replication.
T28 24006-24159 Epistemic_statement denotes The results presented here support a link between PRRSV replication and the altered expression of miR-26a in targeting host innate immune responses (Fig.
T29 24687-24879 Epistemic_statement denotes Overall, these analyses suggest that PRRSV subverts host defenses by inhibiting the expression of pro-inflammatory cytokines (Van Reeth et al., 1999) and stimulating weak production of IFN-␣ .
T30 24880-25128 Epistemic_statement denotes Our results showed that over-expression of miR-26a was capable of inducing expression of IFN-␣/␤ and the IFN-stimulated genes ISG15 and MX1, which might result in activation of the IFN response and further lead to the inhibition of virus infection.
T31 25129-25300 Epistemic_statement denotes The restoration of innate immune responses to produce type I IFNs in PAMs seems to be miRNA specific, because another miRNA (miR-181b) had no such effect (data not shown).
T32 25301-25430 Epistemic_statement denotes Thus, it is possible that miR-26a-induced type I IFN expression can overcome PRRSV interference, contributing to viral clearance.
T33 26445-26556 Epistemic_statement denotes Our results showed that miR-26a also can mediate the activation of IFNs in the absence of PRRSV infection (Fig.
T34 26562-26775 Epistemic_statement denotes The possible causes may relate to recent studies about a new function of miRNAs, which is independent of their conventional role in post-transcriptional gene regulation Fabbri et al., 2012; Lehmann et al., 2012) .
T35 27014-27114 Epistemic_statement denotes Although there is no current evidence, miR-26a may also serve as ligands for TLRs and activate IFNs.
T36 27115-27192 Epistemic_statement denotes Future studies will be necessary to unravel the diverse functions of miR-26a.
T37 27278-27575 Epistemic_statement denotes Although clearly defining the target and physiological role of miR-26a remains an unfinished task, our study provided evidence that over-expression of miR-26a enhances IFN-␣/␤ expression during PRRSV infection, suggesting that miR-26a could be used as a potential target for antiviral development.