The Leader Protein of Cardioviruses Inhibits Stress Granule Assembly

Encephalomyocarditis Virus Disrupts Stress Granules, the Critical Platform for Triggering Antiviral Innate Immune Responses

“…2, and monitored live for distribution of GFP fluorescence (representative results are shown in Movies S1 to S9 in the supplemental material). Cells infected with SeV, IAV, VSV, and TMEV did not show SG formation (8). Other viruses induced SGs, typically forming a large number of small granules at around 5 h postinfection and gradually fusing to each other.…”

“…Virus infection results in the accumulation of doublestranded RNA (dsRNA), thereby activating PKR and phosphorylation of the ␣ subunit of eukaryotic initiation factor 2 (eIF2␣), leading to the formation of stress granules (SGs) (6,7). Several studies have reported the interaction between viruses and SGs, especially the effects of specific types of viruses on the fate of SG formation and how viruses modulate stress granule assembly (8)(9)(10)(11). Recently, we reported that RLR recruitment to SGs during SG formation is critical for RLR-mediated signaling and that nonstructural protein 1 of influenza A virus (IAV) blocks RLR signaling by inhibiting SGs and the antiviral response (12).…”

Solution structures of Mengovirus Leader protein, its phosphorylated derivatives, and in complex with nuclear transport regulatory protein, RanGTPase

“…When complexes were probed, each protein was at 0.5 mM (one labeled and one unlabeled), and the samples were supplemented with (unlabeled) GST-RCC1 (1.4 nmol). 15 N-NOESY (t mix = 150 ms), and 3D 13 C-NOESY (t mix = 140 ms) were collected on a Bruker DRX-600 spectrometer equipped with a 1 H, 13 C, 15 N, 31 P three-axis gradient cryogenic probe. The techniques and algorithms used to process the raw data are detailed in SI Materials and Methods.…”

“…Because picornaviruses replicate in the cytoplasm, this inhibition is detrimental only to the cell. Among the measured results, there is antagonism of IFN transcription (9-12), impediment of cellular stress granule formation (13), and retention of cellular mRNA transcripts in the nucleus (12). These cumulative activities allow cardioviruses to negate almost all host antiviral innate immune responses and enhance their pathogenicity during infection.…”

“…1A). The change is in a conserved, amino-proximal CHCC zinc finger motif (aa [10][11][12][13][14][15][16][17][18][19][20][21][22], the structure of which was determined by NMR for the L M protein (14). Technical difficulties hampered resolution of the complete protein, but a full coordinate set was recently completed [Protein Data Bank (PDB) ID code 2M7Y].…”