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Details on Person West Nile virus (WNV) assembles a replication complex on the...

Class:IdSummation:9691302
_displayNameWest Nile virus (WNV) assembles a replication complex on the...
_timestamp2025-10-13 16:01:11
created[InstanceEdit:9691298] Shamovsky, Veronica, 2020-06-11
literatureReference[LiteratureReference:9690575] 2'-O methylation of the viral mRNA cap evades host restriction by IFIT family members
[LiteratureReference:9684546] Inhibition of translation by IFIT family members is determined by their ability to interact selectively with the 5'-terminal regions of cap0-, cap1- and 5'ppp- mRNAs
[LiteratureReference:9691295] Flaviviral Replication Complex: Coordination between RNA Synthesis and 5'-RNA Capping
[LiteratureReference:9691299] West Nile virus 5'-cap structure is formed by sequential guanine N-7 and ribose 2'-O methylations by nonstructural protein 5
[LiteratureReference:9684553] Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability
[LiteratureReference:9968435] Structures of NS5 Methyltransferase from Zika Virus
[LiteratureReference:9968432] Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation
[LiteratureReference:9946644] Evasion of early innate immune response by 2'-O-methylation of dengue genomic RNA
[LiteratureReference:9684462] Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2'-o-methyltransferase activity
[LiteratureReference:9968364] SARS-CoV-2 Uses Nonstructural Protein 16 To Evade Restriction by IFIT1 and IFIT3
[LiteratureReference:9684554] Rational design of a live attenuated dengue vaccine: 2'-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques
[LiteratureReference:9684481] Innate immune restriction and antagonism of viral RNA lacking 2׳-O methylation
[LiteratureReference:9834866] The methyltransferase domain of the Respiratory Syncytial Virus L protein catalyzes cap N7 and 2'-O-methylation
[LiteratureReference:9968438] Mutational analysis of a multifunctional protein, with mRNA 5' cap-specific (nucleoside-2'-O-)-methyltransferase and 3'-adenylyltransferase stimulatory activities, encoded by vaccinia virus
modified[InstanceEdit:9691522] Shamovsky, Veronica, 2020-06-17
[InstanceEdit:9692472] Shamovsky, Veronica, 2020-06-24
[InstanceEdit:9968444] Shamovsky, Veronica, 2025-10-13
textWest Nile virus (WNV) assembles a replication complex on the cytoplasmic face of the endoplasmic reticulum (ER) membrane to coordinate RNA synthesis, which includes RNA capping and RNA methylation steps producing RNA with a type 1 cap structure (cap-1, m⁷GpppNm-RNA) at its 5'-end (Ray D et al., 2006). The capping process involves four sequential enzymatic activities: RNA triphosphatase, guanylyltransferase, guanine N7-methyltransferase, and 2′-O-methyltransferase (MTase). First, the viral nonstructural protein (NS3) helicase acts as RNA triphosphatase, releasing the terminal phosphate from the 5′ end of the nascent (+) strand RNA. The NS5 protein then transfers GMP moiety from GTP to produce a cap structure and catalyzes sequential N7 and 2′-O methylations of the RNA cap, using S-adenosyl-L-methionine as the methyl donor (Ray D et al., 2006; Klema VJ et al., 2015). 2'-O-methylation of the viral mRNA cap mimics host mRNAs and enables evasion of host restriction by interferon (IFN)-induced proteins with tetratricopeptide repeats (IFITs),specifically IFIT1, which recognizes unmethylated mRNA and prevents their translation (Daffis S et al., 2010; Kumar P et al., 2014). A mutation in NS5 (E218A) abolishes 2′-O-MTase activity and attenuates virus replication in mammalian cells and mice, but pathogenicity is restored in the absence of type I interferon signaling (Daffis S et al., 2010; Kumar P et al. 2014 ). Consistently, doxycycline-induced IFIT1 expression in human embryonic kidney (HEK293 cells restricted infection by the WNV NS5 E218A mutant but not wild-type virus (Johnson B et al., 2018). This Reactome event describes 2'-O methylation of WNV mRNA by viral NS5. Similar 2′-O-MTases are encoded by other flaviviruses, including Zika virus (ZIKV) (Coloma J et al., 2016), Japanese encephalitis virus (JEV) (Li SH et al., 2013), dengue virus (DENV) (Chang DC et al., 2016), coronaviruses such as severe acute respiratory syndrome coronavirus 1 (SARS‑CoV‑1) (Menachery VD et al., 2014), SARS-CoV-2 (Schindewolf C et al., 2023), pneumoviruses such as respiratory syncytial virus (RSV) (Sutto-Ortiz P et al., 2021) and poxviruses such as vaccinia virus (VACV) (Schnierle BS et al., 1994; Daffis S et al., 2010), indicating a widespread viral strategy to generate capped RNA to evade innate immunity (Daffis S et al., 2010; Züst R et al., 2011; Li SH et al., 2013; Menachery VD et al., 2014; reviewed by Hyde JL & Diamond MS 2015).
(summation)[Reaction:9691267] WNV NS5 acts as a cap 2'-O-methyltransferase to modify WNV mRNAs [Homo sapiens]
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