Multiple pro-viral effects of the host protein G3BP in SARS-CoV-2 Infection

<title>Abstract</title> Ras-GTPase-activating protein SH3-domain-binding proteins (G3BP) are multifunctional RNA-binding proteins, pivotal in the initiation of stress granules (SGs). SARS-CoV-2 nucleocapsid (N) protein exhibits strong binding affinity for G3BP and inhibition of SG formation. However, pro-viral role(s) of the G3BP-N interaction have remained unclear. Here, we have comprehensively examined the importance of G3BP for SARS-CoV-2 infection both in vitro and in vivo. Using reverse genetics, we constructed a viral mutant, SARS-CoV-2 RATA, which exhibits stronger and more persistent SG response in infected cells. We also show that in SARS-CoV-2 infected cells, G3BP-N complexes are targeted to the pore complex of double membrane vesicles (DMV) from which nascent viral RNA emerges. Furthermore, through interaction with 40S ribosomal subunits, G3BP-N complexes promote highly localized translation of viral mRNAs at the viral factories and thus facilitate viral gene expression and replication. This work provides a mechanistic understanding of the roles of G3BP in SARS-CoV-2 infection..

Media Type:

Preprint

Year of Publication:

2024

Publication:

2024

Contained In:

ResearchSquare.com - (2024) vom: 06. Dez. To Main Record - year:2024

Language:

English

Contributors:

McInerney, Gerald [Author]
Long, Siwen [Author]
Vidakovics, Laura Perez [Author]
Han, Xiao [Author]
Sun, Renhua [Author]
Wang, Megan [Author]
Panas, Marc [Author]
Urgard, Egon [Author]
Merits, Andres [Author]
Achour, Adnane [Author]
Guzyk, Mykhailo [Author]
Coquet, Jonathan [Author]

Links:

Volltext [lizenzpflichtig]
Volltext [kostenfrei]

Keywords:

570
Biology

doi:

10.21203/rs.3.rs-4145371/v1

funding:

Supporting institution / Project title:

PPN (Catalogue-ID):

XRA043205402