Id |
Subject |
Object |
Predicate |
Lexical cue |
T97 |
0-67 |
Sentence |
denotes |
Interference With the Nucleic Acid Sensing and Downstream Signaling |
T98 |
68-256 |
Sentence |
denotes |
Previous studies on SARS-CoV revealed smart strategies to inhibit multiple steps in the NAS pathway and downstream signaling (Rose et al., 2010; Adedeji et al., 2013; Chan and Gack, 2016). |
T99 |
257-326 |
Sentence |
denotes |
As mentioned earlier, TRIM25 mediated ubiquitination activates RIG-I. |
T100 |
327-454 |
Sentence |
denotes |
Whereas, the N protein of SARS-CoV, which binds to TRIM25 and thereby prevents its association with RIG-I and hence activation. |
T101 |
455-579 |
Sentence |
denotes |
The ubiquitin usurped RIG-I is unable to mount the antiviral response, thereby disabling IFN-β production (Hu et al., 2017). |
T102 |
580-795 |
Sentence |
denotes |
N protein also antagonizes IFN signaling by directly interacting with IRF3, thereby inhibiting its phosphorylation and subsequent nuclear translocation (Kopecky-Bromberg et al., 2006; Kopecky-Bromberg et al., 2007). |
T103 |
796-943 |
Sentence |
denotes |
Similarly, M protein inhibits IRF3/IRF7 signaling by interfering with RIG-I, TBK1, IKKε, and TRAF3 activation complex formation (Siu et al., 2009). |
T104 |
944-1172 |
Sentence |
denotes |
Acting at multiple pathways on host cells, Nsp1 inhibits IFN-β promoter activity and STAT1 phosphorylation which led to a decrease in the expression of various antiviral interferon-stimulated genes (ISGs; Wathelet et al., 2007). |
T105 |
1173-1343 |
Sentence |
denotes |
Chen et al. (2014) showed that papain-like protease (PLpro) directly associates with TRAF3, TBK1, IKKε, STING, and IRF3 and hence inhibits downstream IRF3/IRF7 signaling. |
T106 |
1344-1473 |
Sentence |
denotes |
In another study, Devaraj et al. (2007) showed that PLpro inhibits IRF3 phosphorylation and its subsequent nuclear translocation. |
T107 |
1474-1679 |
Sentence |
denotes |
ORF3b, ORF6, ORF8a, and ORF8b also play prominent roles in inhibiting IRF3 phosphorylation and its subsequent nuclear translocation (Kopecky-Bromberg et al., 2006; Freundt et al., 2010; Wong et al., 2018). |
T108 |
1680-1869 |
Sentence |
denotes |
ORF9b was shown to be associated with mitochondria and induced degradation of dynamin-related protein 1 (Drp1), thus altering mitochondrial function and sequestering MAVS into small puncta. |
T109 |
1870-2083 |
Sentence |
denotes |
Further, ORF9b was associated with recruitment of ubiquitin ligases PCBP2 and AIP4 E3 which led to ubiquitination of MAVS and eventually its degradation, as a result inhibiting IFN-β production (Shi et al., 2014). |
T110 |
2084-2238 |
Sentence |
denotes |
Thus, by associating with multiple proteins involved in NAS signaling, SARS-CoV antagonizes IFN signaling and synthesis of protective molecules like ISGs. |
T111 |
2239-2393 |
Sentence |
denotes |
Recent studies have also demonstrated the interaction of SARS-CoV-2 proteins with multiple host cell NAS signaling molecules and downstream IFN signaling. |
T112 |
2394-2518 |
Sentence |
denotes |
An extensive proteomic study by Gordon et al. (2020), showed multiple SARS-CoV-2 protein and host cell protein interactions. |
T113 |
2519-2617 |
Sentence |
denotes |
A proteome map of 26 SARS-CoV-2 proteins predicted 332 viral proteins interacting with host cells. |
T114 |
2618-2761 |
Sentence |
denotes |
Among these, Nsp9, Nsp13, Nsp15, ORF3a, ORF9b, and ORF9c interacted with proteins in downstream NAS signaling, IFN response, and NF-κB pathway. |
T115 |
2762-2977 |
Sentence |
denotes |
Similarly, Nsp5 interacted with HDAC2, which may be thus involved in limiting the IFN signaling and inflammatory response, but the specific functional role of these proteins was not determined (Gordon et al., 2020). |
T116 |
2978-3072 |
Sentence |
denotes |
In two recent studies, the functional relevance of some of these proteins was tested in vitro. |
T117 |
3073-3263 |
Sentence |
denotes |
In the first study, Li J.Y. et al. (2020) tested the effects of ORF6, ORF8 and N protein on the antiviral response in HEK293 cells and found these proteins inhibit IFN-β and NF-κB signaling. |
T118 |
3264-3431 |
Sentence |
denotes |
Similarly, Yuen et al. (2020) showed that IFN antagonizing effect of ORF6 was due to its association with the interferon-inducible nuclear export complex (NUP98–RAE1). |
T119 |
3432-3577 |
Sentence |
denotes |
The study further showed that Nsp13, Nsp14, and Nsp15 could also antagonize IFN response, but the mechanism was not explored (Yuen et al., 2020). |
T120 |
3578-3710 |
Sentence |
denotes |
In addition to interfering with IFN production pathway, SARS-CoV has evolved multiple other mechanisms to modify host cell response. |
T121 |
3711-3860 |
Sentence |
denotes |
Viral RNA is unprotected and open to cellular degradation; however, some RNA viruses have evolved a capping process to evade recognition by the host. |
T122 |
3861-4013 |
Sentence |
denotes |
In SARS-CoV, Nsp16 provides ribose 2′-O-methylation at the 5′ end of the RNA to protect its degradation and prevent sensing by MDA5 (Züst et al., 2011). |
T123 |
4014-4122 |
Sentence |
denotes |
Similarly, Nsp14 had N7 methyltransferase activity and methylated the 5′ end of the RNA (Chen et al., 2009). |
T124 |
4123-4282 |
Sentence |
denotes |
Other SARS-CoV proteins involved include – Nsp4a, which prevents stress granule formation by inhibiting PKR mediated antiviral signaling (Rabouw et al., 2016). |
T125 |
4283-4413 |
Sentence |
denotes |
N protein of SARS-CoV-2 is also known to interact with the proteins implicated in stress granule regulation (Gordon et al., 2020). |
T126 |
4414-4647 |
Sentence |
denotes |
Electron tomography studies in SARS-CoV infected cells revealed a unique replication network derived from ER to organize viral replication while simultaneously hiding the viral RNA from recognition by host NASs (Knoops et al., 2008). |
T127 |
4648-4854 |
Sentence |
denotes |
Other RNA viruses have also developed similar strategies to evade sensing by forming double-membrane vesicles (DMVs) and replication organelles to prevent access to the NASs (Blanchard and Roingeard, 2015). |