Ebola virus VP35 blocks stress granule assembly

Sage, Valerie Le; Cinti, Alessandro; McCarthy, Stephen D.S.; Amorim, Raquel Beltrão; Rao, Shringar; Daino, Gian Luca; Tramontano, Enzo; Branch, Donald R.; Mouland, Andrew J.

doi:10.1016/j.virol.2016.12.012

Cited by 54 publications

(48 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overexpression of G3BP1 induces SG formation (Tourriere et al, 2003). Cleavage of G3BP1 by viral protease or sequestering of G3BP1 by viral proteins inhibits formation of SGs (Le Sage et al, 2017;Nelson et al, 2016;White et al, 2007). Here we observed that while knockdown of G3BP1 enhanced PEDV replication, overexpression of G3BP1 reduced PEDV replication in Vero cells.…”

Section: Discussionmentioning

confidence: 59%

“…Some virus infections cause SGs and the formation of SGs is considered as an indication of an antiviral innate response that limits translation of the viral genes (Onomoto et al, 2014). Many viruses have evolved strategies to overcome the antiviral effect of SGs by degrading or sequestering its key components such as G3BP1 or TIA-1/TIAR to prevent the formation of SGs (Emara and Brinton, 2007;Humoud et al, 2016;Le Sage et al, 2017;Nelson et al, 2016;White et al, 2007;White and Lloyd, 2011). The nonstructural protein 1 (NS1) of influenza A virus (IAV) inhibits eIF-2α phosphorylation mediated SGs by blocking PKR activation (Khaperskyy et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

GTPase-activating protein-binding protein 1 (G3BP1) plays an antiviral role against porcine epidemic diarrhea virus

Pandey¹,

Zhong²,

Diel

et al. 2019

Veterinary Microbiology

View full text Add to dashboard Cite

Porcine epidemic diarrhoea virus (PEDV) is a single-stranded, positive-sense RNA virus that belongs to the Coronaviridae. PEDV causes severe diarrhoea and dehydration in nursing piglets, which leads to significant economic losses to the swine industry worldwide. Stress granules (SGs) are sites of mRNA storage that are formed under various stress conditions including viral infections. Increasing evidence suggests that SGs function in antiviral innate immunity of host cells to limit virus replication. Ras-GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) is a key stress granule-resident protein that nucleates stress granule assembly. Depletion of G3BP1 inhibits SGs formation and overexpression of G3BP1 nucleates SGs assembly. We observed that knockdown of G3BP1 by silencing RNA significantly increased PEDV replication. Overexpression of exogenous G3BP1, on the other hand, lowered virus replication by 100-fold compared to vector control. An increase in the levels of mRNAs of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) was also observed in PEDV-infected G3BP1 depleted cells compared to PEDV-infected control cells. Taken together, our results suggest that G3BP1 plays an antiviral role and impairs PEDV replication.

show abstract

Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

GTPase-activating protein-binding protein 1 (G3BP1) plays an antiviral role against porcine epidemic diarrhea virus

Pandey¹,

Zhong²,

Diel

et al. 2019

Veterinary Microbiology

View full text Add to dashboard Cite

show abstract

“…mRNAs from filoviruses (those encoding VP35, VP30, VP24 and L) contain initiation sequences similar to those found in the host proteins that remain present after cellular stress, thus shifting host translation towards the production of viral mRNAs, a phenomenon that is supported by the lack of stress granule formation in EBOV-infected cells [115][116][117] .…”

Section: Convalescent Serummentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

View full text Add to dashboard Cite

| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

show abstract

“…These organelles also regulate mRNA stability and have antiviral functions (reviewed in reference 138). Viruses use various strategies to disrupt or block stress granules; for example, Ebola virus inhibits SG formation (139), influenza virus sequesters double-stranded RNA (dsRNA) to prevent SG initiation (140), and poliovirus 3 C protease cleaves a major SG protein, Ras GTPase-activating protein-binding protein 1 (G3BP1) (141). The RNA-binding PARP12 and -13 are found in stress granules, where PARP12 is responsible for MARylation of various proteins such as the argonaute proteins, G3BP1, and TIA-1 (36).…”

Section: Parps As Transcription Factor Coactivators/corepressorsmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Brady

Goel

Johnson

2019

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

SUMMARYThe literature review presented here details recent research involving members of the poly(ADP-ribose) polymerase (PARP) family of proteins. Among the 17 recognized members of the family, the human enzyme PARP1 is the most extensively studied, resulting in a number of known biological and metabolic roles. This review is focused on the roles played by PARP enzymes in host-pathogen interactions and in diseases with an associated inflammatory response. In mammalian cells, several PARPs have specific roles in the antiviral response; this is perhaps best illustrated by PARP13, also termed the zinc finger antiviral protein (ZAP). Plant stress responses and immunity are also regulated by poly(ADP-ribosyl)ation. PARPs promote inflammatory responses by stimulating proinflammatory signal transduction pathways that lead to the expression of cytokines and cell adhesion molecules. Hence, PARP inhibitors show promise in the treatment of inflammatory disorders and conditions with an inflammatory component, such as diabetes, arthritis, and stroke. These functions are correlated with the biophysical characteristics of PARP family enzymes. This work is important in providing a comprehensive understanding of the molecular basis of pathogenesis and host responses, as well as in the identification of inhibitors. This is important because the identification of inhibitors has been shown to be effective in arresting the progression of disease.

show abstract

Ebola virus VP35 blocks stress granule assembly

Cited by 54 publications

References 60 publications

GTPase-activating protein-binding protein 1 (G3BP1) plays an antiviral role against porcine epidemic diarrhea virus

GTPase-activating protein-binding protein 1 (G3BP1) plays an antiviral role against porcine epidemic diarrhea virus

Post-exposure treatments for Ebola and Marburg virus infections

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Contact Info

Product

Resources

About