Picornavirus 2A Protease Disrupts G3BP-eIF4GI Interaction That Initiates Typical Stress Granule Formation

2018 ◽  
Author(s):  
Xiaodan Yang ◽  
Zhulong Hu ◽  
Shanshan Fan ◽  
Qiang Zhang ◽  
Yi Zhong ◽  
...  
Keyword(s):  
Stress Granule ◽  
Granule Formation ◽  
2A Protease

scholarly journals Picornavirus 2A protease regulates stress granule formation to facilitate viral translation

2018 ◽  
Vol 14 (2) ◽  
pp. e1006901 ◽  
Author(s):  
Xiaodan Yang ◽  
Zhulong Hu ◽  
Shanshan Fan ◽  
Qiang Zhang ◽  
Yi Zhong ◽  
...  
Keyword(s):  
Stress Granule ◽  
Granule Formation ◽  
Viral Translation ◽  
2A Protease

scholarly journals The Leader Protein of Theiler's Virus Prevents the Activation of PKR

2019 ◽  
Vol 93 (19) ◽  
Author(s):  
Fabian Borghese ◽  
Frédéric Sorgeloos ◽  
Teresa Cesaro ◽  
Thomas Michiels
Keyword(s):  
Stress Granule ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Wild Type Virus ◽  
Granule Formation ◽  
Double Stranded Rna ◽  
Eif2α Phosphorylation ◽  
Leader Protein ◽  
Infected Cells ◽  
L Proteins

ABSTRACT Leader (L) proteins encoded by cardioviruses are multifunctional proteins that contribute to innate immunity evasion. L proteins of Theiler’s murine encephalomyelitis virus (TMEV), Saffold virus (SAFV), and encephalomyocarditis virus (EMCV) were reported to inhibit stress granule assembly in infected cells. Here, we show that TMEV L can act at two levels in the stress granule formation pathway: on the one hand, it can inhibit sodium arsenite-induced stress granule assembly without preventing eIF2α phosphorylation and, thus, acts downstream of eIF2α; on the other hand, it can inhibit eucaryotic translation initiation factor 2 alpha kinase 2 (PKR) activation and the consequent PKR-mediated eIF2α phosphorylation. Interestingly, coimmunostaining experiments revealed that PKR colocalizes with viral double-stranded RNA (dsRNA) in cells infected with L-mutant viruses but not in cells infected with the wild-type virus. Furthermore, PKR coprecipitated with dsRNA from cells infected with L-mutant viruses significantly more than from cells infected with the wild-type virus. These data strongly suggest that L blocks PKR activation by preventing the interaction between PKR and viral dsRNA. In infected cells, L also rendered PKR refractory to subsequent activation by poly(I·C). However, no interaction was observed between L and either dsRNA or PKR. Taken together, our results suggest that, unlike other viral proteins, L indirectly acts on PKR to negatively regulate its responsiveness to dsRNA. IMPORTANCE The leader (L) protein encoded by cardioviruses is a very short multifunctional protein that contributes to evasion of the host innate immune response. This protein notably prevents the formation of stress granules in infected cells. Using Theiler’s virus as a model, we show that L proteins can act at two levels in the stress response pathway leading to stress granule formation, the most striking one being the inhibition of eucaryotic translation initiation factor 2 alpha kinase 2 (PKR) activation. Interestingly, the leader protein appears to inhibit PKR via a novel mechanism by rendering this kinase unable to detect double-stranded RNA, its typical activator. Unlike other viral proteins, such as influenza virus NS1, the leader protein appears to interact with neither PKR nor double-stranded RNA, suggesting that it acts indirectly to trigger the inhibition of the kinase.

scholarly journals Puumala and Andes Orthohantaviruses Cause Transient Protein Kinase R-Dependent Formation of Stress Granules

2019 ◽  
Vol 94 (3) ◽  
Author(s):  
Wanda Christ ◽  
Janne Tynell ◽  
Jonas Klingström
Keyword(s):  
Protein Kinase ◽  
Host Cell ◽  
Stress Responses ◽  
Stress Granules ◽  
Cell Stress ◽  
Stress Granule ◽  
Hantavirus Infection ◽  
Stress Signaling ◽  
Protein Kinase R ◽  
Granule Formation

ABSTRACT Virus infection frequently triggers host cell stress signaling resulting in translational arrest; as a consequence, many viruses employ means to modulate the host stress response. Hantaviruses are negative-sense, single-stranded RNA viruses known to inhibit host innate immune responses and apoptosis, but their impact on host cell stress signaling remains largely unknown. In this study, we investigated activation of host cell stress responses during hantavirus infection. We show that hantavirus infection causes transient formation of stress granules (SGs) but does so in only a limited proportion of infected cells. Our data indicate some cell type-specific and hantavirus species-specific variability in SG prevalence and show SG formation to be dependent on the activation of protein kinase R (PKR). Hantavirus infection inhibited PKR-dependent SG formation, which could account for the transient nature and low prevalence of SG formation observed during hantavirus infection. In addition, we report only limited colocalization of hantaviral proteins or RNA with SGs and show evidence indicating hantavirus-mediated inhibition of PKR-like endoplasmic reticulum (ER) kinase (PERK). IMPORTANCE Our work presents the first report on stress granule formation during hantavirus infection. We show that hantavirus infection actively inhibits stress granule formation, thereby escaping the detrimental effects on global translation imposed by host stress signaling. Our results highlight a previously uncharacterized aspect of hantavirus-host interactions with possible implications for how hantaviruses are able to cause persistent infection in natural hosts and for pathogenesis.

scholarly journals Both G3BP1 and G3BP2 contribute to stress granule formation

2012 ◽  
Vol 18 (2) ◽  
pp. 135-146 ◽  
Author(s):  
Hideaki Matsuki ◽  
Masahiko Takahashi ◽  
Masaya Higuchi ◽  
Grace N Makokha ◽  
Masayasu Oie ◽  
...  
Keyword(s):  
Stress Granule ◽  
Granule Formation

Emetine‐Loaded Black Phosphorus Hydrogel Sensitizes Tumor to Photothermal Therapy through Inhibition of Stress Granule Formation

2020 ◽  
Vol 30 (43) ◽  
pp. 2003891
Author(s):  
Jianlei Xie ◽  
Taojian Fan ◽  
Ji Hyeon Kim ◽  
Yunjie Xu ◽  
Yingwei Wang ◽  
...  
Keyword(s):  
Photothermal Therapy ◽  
Black Phosphorus ◽  
Stress Granule ◽  
Granule Formation

scholarly journals Viral and Cellular Proteins Containing FGDF Motifs Bind G3BP to Block Stress Granule Formation

2015 ◽  
Vol 11 (2) ◽  
pp. e1004659 ◽  
Author(s):  
Marc D. Panas ◽  
Tim Schulte ◽  
Bastian Thaa ◽  
Tatiana Sandalova ◽  
Nancy Kedersha ◽  
...  
Keyword(s):  
Stress Granule ◽  
Cellular Proteins ◽  
Granule Formation
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