Ras GTPase-activating protein-binding protein 1 (G3BP1)

[Hutan]

Ras GTPase activating protein binding protein 1

This molecule was mentioned in a paper - levels of the molecule were used as a measure of cell stress (higher levels correlated with higher cell stress):
Molecular mechanisms of stress-induced reactivation in mumps virus condensates, 2023, Xiaojie Zhang et al

In that paper, this protein was used as marker of cell stress, and levels of it were found to be correlated with levels of viral reactivation.

 

[Hutan]

Edit - the RAS GTPase-activating protein 1 and the RAS GTPase-activating protein-binding protein 1 are fact different, despite the very similar names. So, ignore this post. See later post.

[Googling to see if anyone has reported on Ras GTPase activating protein-binding protein in ME/CFS, I see that Erin Sweetman's paper (2020) did:
"RAS GTPase-activating protein 1; P value 0.0053; fold change 0.63"
from gene RASA1
I think that's the same protein.

So it was decreased, and with a good P-value even though the number of participants was small.

The study looked at the "proteomes of peripheral blood mononuclear cells (PBMCs) by SWATH-MS analysis in a small well-characterised group of patients and matched controls". Only 11 ME/CFS participants.]

 

[Hutan]

There's this study
GTPase-activating protein-binding protein 1 (G3BP1) plays an antiviral role against porcine epidemic diarrhea virus, 2019, Pandey et al

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.

It's suggesting that reduced G3BP1 reduces stress granule formation and increases the success of a virus in replicating in pigs. Therefore, cells with lower G3BP1, as were found in that small Sweetman study of ME/CFS peripheral blood mononuclear cells, might be likely to be less good at preventing viral replication.

Could the infecting virus be down-regulating G3BP1? And/or could there be a genetically caused reduction in G3BP1?

(In this case, low levels of G3BP1 seemed to result in viral replication; the paper in the first post found that high levels of it indicated a stressed cell, and was correlated with high levels of viral replication.)

Sorry for this, there isn't a coherent narrative, I'm thinking out loud here. Feel free to participate.

 

[Hutan]

Reading the discussion in the paper linked to in the first post of this thread, it sounds as though different viruses employ different strategies in relation to G3BP1 and stress granules. Combine that with different host genetics and environment, and that could explain the seemingly different findings.

That's also noted in the paper linked in the post above:
[QUOTE="Pandey et al)]Stress granules (SGs) are dynamic cytoplasmic foci that form in response to different stress conditions including virus infections (Kedersha and Anderson, 2002). 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).

Some viruses have been reported to benefit from SGs formation. For instance, respiratory syncytial virus (RSV) replication was impaired in cells with a reduced level of G3BP1 expression (Lindquist et al., 2010[/QUOTE]

 

[Hutan]

Erin Sweetman's paper (2020) did:
"RAS GTPase-activating protein 1; P value 0.0053; fold change 0.63"
from gene RASA1
I think that's the same protein.

So it was decreased, and with a good P-value even though the number of participants was small.

The study looked at the "proteomes of peripheral blood mononuclear cells (PBMCs) by SWATH-MS analysis in a small well-characterised group of patients and matched controls". Only 11 ME/CFS participants.]

I made this thread mostly because I thought the protein that seemed to be closely tied to viral persistence was the same as the protein that was found to be significantly reduced in ME/CFS immune cells in the Sweetman paper. But they aren't the same proteins. RAS GTPase-activating protein 1 is not the same as the RAS GTPase-activating protein binding-protein 1 (the topic of this thread).
p120-RasGAP is a synonym for RAS GTPase-activating protein 1.

 

[Hutan]

Ok, just to make this thread completely confusing:
It turns out that there's a 2019 paper by Sweetman that mention G3BP2 (note the 2, not 1)
Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome, 2019, Sweetman et al
Forum thread here
Peripheral blood mononuclear cells, examining the transcriptomes, quantifying RNA. 10 people with ME/CFS; 10 healthy controls.
And G3BP2 is there in Table1, one of 27 genes with altered expression,

G3BP2; G3BP Stress granule assembly factor 2; P value 4.5 × 10−3; Fold change 2.0

Scaffold protein that plays an essential role in cytoplasmic stress granule formation which acts as a platform for antiviral signaling.

So, that suggests that G3BP1 could be increased in ME/CFS.