eEF2 and Ras-GAP SH3 domain-binding protein (G3BP1) modulate stress granule assembly during HIV-1 infection

Valiente-Echeverría, Fernando; Melnychuk, Luca; Vyboh, Kishanda; Ajamian, Lara; Gallouzi, Imed Eddine; Bernard, Nicole F.; Mouland, Andrew J.

doi:10.1038/ncomms5819

Cited by 73 publications

(93 citation statements)

References 69 publications

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“…The N-terminal Capsid domain of Gag (precursor viral polyprotein, processed into different viral proteins during maturation) interacts with eukaryotic elongation factor 2 (eEF2) to block SGs formation. To dismantle the already formed SGs, Gag recruits G3BP1 out the SGs (by displacing eEF2 with G3BP1) [116]. Infection with Rubella virus has also been shown to change the localization of host G3BPs, indicating that G3BPs may play an important role during infection by Rubella [117].…”

Section: Viral Targeting Of G3bps By Protein Interactionsmentioning

confidence: 99%

Rasputin a decade on and more promiscuous than ever? A review of G3BPs

Alam

Kennedy

2019

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Section: Viral Targeting Of G3bps By Protein Interactionsmentioning

confidence: 99%

Rasputin a decade on and more promiscuous than ever? A review of G3BPs

Alam

Kennedy

2019

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…chemical inhibitor of translation elongation and a well-characterized bona fide inhibitor of SG formation [20,32,50,51]. Given that the doses of CHX previously used to prevent SG formation (~100 lg/ml) also affect general translation to levels that are similar to AS treatment ( Fig 2B) [32,49,[51][52][53], we first determined the minimum dose of CHX that could prevent SG assembly without affecting the levels of newly synthesized proteins. We observed that 0.5 lg/ml of CHX for 30 min was sufficient to prevent both the formation of SGs ( Fig 4A) and the AS-mediated impairment of senescence in human fibroblasts ( Fig 4B and Appendix Fig S6).…”

Section: Sg Formation In the Proliferative Stage Prevents Cell Commitmentioning

confidence: 99%

Stress granules counteract senescence by sequestration of PAI‐1

et al. 2018

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Cellular senescence is a physiological response by which an organism halts the proliferation of potentially harmful and damaged cells. However, the accumulation of senescent cells over time can become deleterious leading to diseases and physiological decline. Our data reveal a novel interplay between senescence and the stress response that affects both the progression of senescence and the behavior of senescent cells. We show that constitutive exposure to stress induces the formation of stress granules (SGs) in proliferative and presenescent cells, but not in fully senescent cells. Stress granule assembly alone is sufficient to decrease the number of senescent cells without affecting the expression of bona fide senescence markers. SG‐mediated inhibition of senescence is associated with the recruitment of the plasminogen activator inhibitor‐1 (PAI‐1), a known promoter of senescence, to these entities. PAI‐1 localization to SGs increases the translocation of cyclin D1 to the nucleus, promotes RB phosphorylation, and maintains a proliferative, non‐senescent state. Together, our data indicate that SGs may be targets of intervention to modulate senescence in order to impair or prevent its deleterious effects.

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“…Because HIV-1 Gag was recently reported to inhibit SG formation 33,34 , we also tested the effects of treating HeLa.YFP-A3G or HeLa.YFP-TIA1 biosensor cells with Ars at 31 hpi when NL4-3 Gag expression in HeLa cells is relatively high ( e.g. , see 31 ).…”

Section: Resultsmentioning

confidence: 99%

HIV-1 RNA genomes initiate host protein packaging in the cytosol independently of Gag capsid proteins

Becker

Evans

Benner

et al. 2019

Preprint

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17HIV-1 RNA genomes interact with diverse RNA binding proteins in the cytoplasm 18 including antiviral factor APOBEC3G (A3G) that, in the absence of viral Vif proteins, is 19 packaged into virions. When and where genome-A3G interactions are initiated in the host 20 cell is unknown. Here we use quantitative long-term (>24 h) live cell fluorescence video 21 microscopy and a new in-cell RNA-protein interaction assay (the "IC-IP") to describe 22 subcellular viral and A3G trafficking behaviors over the entire HIV-1 productive phase. 23Among other findings, we demonstrate that genome-A3G interactions are initiated in the 24 cytosol soon if not immediately after genome nuclear export; that A3G-genome 25 interactions are sufficiently strong so that tethering either factor to membranes inhibits 26 trafficking of the reciprocal binding partner; and that selective recognition of genomes 27 promotes consistent delivery of A3G to sites of virion assembly. Further elucidation of 28 RNA signature(s) detected by A3G may inform development of RNA-targeted antivirals. 29 RNA-and NC-dependent15-20. However, the relative contributions of genomes vs. host 50RNAs to this process remains controversial. On the one hand, A3G-RNA binding is 51 relatively promiscuous, with A3G incorporated into virus particles even when packageable 52 genomes are not expressed17,19. On the other hand, A3G incorporation levels are 53 moderately enhanced when genomes are present16,21; and A3G has been shown to 54 exhibit selective RNA-binding characteristics19,22 including a reported preference for G-55 rich segments of the HIV-1 genome20. 56Where and when A3G interfaces with Gag and/or genomes in the cell has also been 57 under investigation for some time with conflicting results. At steady-state, A3G is 58 distributed throughout the cytosol (the aqueous phase of the cytoplasm) and accumulates 59 to high levels at non-membranous cytoplasmic sites of mRNA decay known as processing 60 bodies (PBs)23,24. Cytosolic A3G is also rapidly re-localized to sites of translational 61 repression known as stress granules (SGs) in response to heat shock or oxidative 62 stress23,24. Initial studies proposed a functional link between PBs and A3G's antiviral 63 activity23,25,26. By contrast, more recent work has shown visible PBs to have little to no 64 discernible relevance to the HIV-1 life cycle27,28. 65The dynamic and complex nature of cytoplasmic RNA trafficking during HIV-1 virion 66 genesis may have obscured consistent prior observations made in fixed cells, 67 emphasizing a need for real-time characterization the host RBP response to HIV-1 68 infection at subcellular resolution. Accordingly, herein we set out to comprehensively 69 define the behaviors of HIV-1 RNA genomes, Gag, A3G, and additional PB and SG 70 markers over the entire viral productive phase using long-term (>24h) live cell video 71 microscopy. Our results expose single-cell A3G degradation and trafficking behaviors in 72 the presence or absence of Vif; and show that HIV-1 infection has little to no ne...

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eEF2 and Ras-GAP SH3 domain-binding protein (G3BP1) modulate stress granule assembly during HIV-1 infection

Cited by 73 publications

References 69 publications

Rasputin a decade on and more promiscuous than ever? A review of G3BPs

Rasputin a decade on and more promiscuous than ever? A review of G3BPs

Stress granules counteract senescence by sequestration of PAI‐1

HIV-1 RNA genomes initiate host protein packaging in the cytosol independently of Gag capsid proteins

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