LitCovid-sentences  

PMC:7200337 / 5990-11401 JSONTXT 9 Projects

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Id Subject Object Predicate Lexical cue
T34 0-42 Sentence denotes Evasion of Innate Sensing by Coronaviruses
T35 43-186 Sentence denotes As these cytokines represent a major barrier to viral infection, CoVs have evolved several mechanisms to inhibit IFN-I induction and signaling.
T36 187-369 Sentence denotes Numerous studies have demonstrated that SARS-CoV-1 suppresses IFN release in vitro and in vivo (Cameron et al., 2012, Minakshi et al., 2009, Siu et al., 2009, Wathelet et al., 2007).
T37 370-573 Sentence denotes SARS-CoV-2 likely achieves a similar effect, as suggested by the lack of robust type I/III IFN signatures from infected cell lines, primary bronchial cells, and a ferret model (Blanco-Melo et al., 2020).
T38 574-723 Sentence denotes In fact, patients with severe COVID-19 demonstrate remarkably impaired IFN-I signatures as compared to mild or moderate cases (Hadjadj et al., 2020).
T39 724-933 Sentence denotes As is often the case, there are multiple mechanisms of evasion for CoVs, with viral factors antagonizing each step of the pathway from PRR sensing and cytokine secretion to IFN signal transduction (Figure 1 ).
T40 934-1013 Sentence denotes Figure 1 Mechanisms of Host Innate Immune Response and Coronaviruses Antagonism
T41 1014-1188 Sentence denotes Overview of innate immune sensing (left) and interferon signaling (right), annotated with the known mechanisms by which SARS-CoV-1 and MERS-CoV antagonize the pathways (red).
T42 1189-1505 Sentence denotes CoV-mediated antagonism of innate immunity begins with evasion of PRR sensing. ssRNA viruses, like CoVs, form dsRNA intermediates during their replication, which can be detected by TLR3 in the endosome and RIG-I, MDA5, and PKR in the cytosol. ssRNA may also be detected by TLR7 or TLR8 and potentially RIG-I and PKR.
T43 1506-1739 Sentence denotes CoVs are known to avoid PRR activation by either avoiding recognition altogether or antagonizing PRR action (Bouvet et al., 2010, Chen et al., 2009, Deng et al., 2017, Hackbart et al., 2020, Ivanov et al., 2004, Knoops et al., 2008).
T44 1740-1881 Sentence denotes To evade PRRs, dsRNA is first shielded by membrane-bound compartments that form during viral replication of SARS-CoV-1 (Knoops et al., 2008).
T45 1882-2171 Sentence denotes In addition, viral RNA is guanosine-capped and methylated at the 5′ end by CoVs non-structural proteins (NSPs) 10, 13, 14, and 16 (Bouvet et al., 2010, Chen et al., 2009, Ivanov et al., 2004), thereby resembling host mRNA to promote translation, prevent degradation, and evade RLR sensing.
T46 2172-2373 Sentence denotes Finally, CoVs also encode an endoribonuclease, NSP15, that cleaves 5′ polyuridines formed during viral replication, which would otherwise be detected by MDA5 (Deng et al., 2017, Hackbart et al., 2020).
T47 2374-2443 Sentence denotes CoVs have evolved additional strategies to impede activation of PRRs.
T48 2444-2519 Sentence denotes SARS-CoV-1 N-protein prevents TRIM25 activation of RIG-I (Hu et al., 2017).
T49 2520-2718 Sentence denotes Likewise, MERS-CoV NS4a, which itself binds dsRNA, impedes PKR activation (Comar et al., 2019, Rabouw et al., 2016) and inhibits PACT, an activator of RLRs (Niemeyer et al., 2013, Siu et al., 2014).
T50 2719-2820 Sentence denotes Additionally, MERS-CoV NS4b antagonizes RNaseL, another activator of RLRs (Thornbrough et al., 2016).
T51 2821-2860 Sentence denotes The role of other PRRs remains unclear.
T52 2861-3015 Sentence denotes For example, SARS-CoV-1 papain-like protease (PLP) antagonizes STING, suggesting that self-DNA may also represent an important trigger (Sun et al., 2012).
T53 3016-3104 Sentence denotes The extent to which SARS-CoV-2 homologs overlap in these functions is currently unknown.
T54 3105-3362 Sentence denotes Following activation, RLR and TLRs induce signaling cascades, leading to the phosphorylation of transcription factors, such as NF-kB and the interferon-regulatory factor family (IRF), ultimately leading to transcription of IFN and proinflammatory cytokines.
T55 3363-3557 Sentence denotes Although no experimental studies have delineated the precise functions of SARS-CoV-2 proteins, proteomic studies have demonstrated interactions between viral proteins and PRR signaling cascades.
T56 3558-3779 Sentence denotes SARS-CoV-2 ORF9b indirectly interacts with the signaling adaptor MAVS via its association with Tom70 (Gordon et al., 2020), consistent with prior reports that SARS-CoV-1 ORF9b suppresses MAVS signaling (Shi et al., 2014).
T57 3780-3942 Sentence denotes Furthermore, SARS-CoV-2 NSP13 interacts with signaling intermediate TBK1, and NSP15 is associated with RNF41, an activator of TBK1 and IRF3 (Gordon et al., 2020).
T58 3943-4085 Sentence denotes Similarly, SARS-CoV-1 M protein is known to inhibit the TBK1 signaling complex (Siu et al., 2009), as does MERS-CoV ORF4b (Yang et al., 2015).
T59 4086-4255 Sentence denotes Other proteins, including SARS-CoV-1 PLP, N, ORF3b, and ORF6, block IRF3 phosphorylation and nuclear translocation (Devaraj et al., 2007, Kopecky-Bromberg et al., 2007).
T60 4256-4296 Sentence denotes NF-kB is also inhibited by CoV proteins.
T61 4297-4423 Sentence denotes These include SARS-CoV-1 PLP (Frieman et al., 2009) and MERS-CoV ORF4b and ORF5 (Canton et al., 2018, Menachery et al., 2017).
T62 4424-4654 Sentence denotes Finally, SARS-CoV-1 NSP1 (Huang et al., 2011a, Kamitani et al., 2009) and MERS-CoV NSP1 (Lokugamage et al., 2015) initiate general inhibition of host transcription and translation, thus limiting antiviral defenses nonspecifically.
T63 4655-4876 Sentence denotes To prevent signaling downstream of IFN release, CoV proteins inhibit several steps of the signal transduction pathway that bridge the receptor subunits (IFNAR1 and IFNAR2) to the STAT proteins that activate transcription.
T64 4877-5144 Sentence denotes For SARS-CoV-1, these mechanisms include IFNAR1 degradation by ORF3a (Minakshi et al., 2009), decreased STAT1 phosphorylation by NSP1 (Wathelet et al., 2007), and antagonism of STAT1 nuclear translocation by ORF6 (Frieman et al., 2007, Kopecky-Bromberg et al., 2007).
T65 5145-5267 Sentence denotes However, SARS-CoV-2 ORF6 shares only 69% sequence homology with SARS-CoV-1, suggesting this function may not be conserved.
T66 5268-5411 Sentence denotes In support of this notion, SARS-CoV-2 infection fails to limit STAT1 phosphorylation, unlike in SARS-CoV-1 infection (Lokugamage et al., 2020).