The Interaction Between Host G3BP and Viral Nucleocapsid Protein Regulates SARS-CoV-2 Replication

<p>G3BP1/2 are RNA-binding proteins that promote condensation to form stress granules in response to various cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP-N interaction in the context of viral infection have remained unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively disrupt their interaction. We found that mutation of N-F17 led to selective loss of interaction with G3BP1 and consequent failure of the N protein to disrupt stress granule assembly. Introduction of SARS-CoV-2 bearing an F17A mutation in an in vivo hamster model resulted in significant decreases in viral replication, symptom severity, and pathology, suggesting that the G3BP1-N interaction promotes viral replication by suppressing the ability of G3BP1 to form stress granules.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.available

2023

Author dc:creator

• Yang, Zemin

Contributors dc:contributor

• J. Paul Taylor, MD, PhD

• G3BP
• Nucleocapsid Protein
• SARS-CoV-2
• Stress Granule
• Viral Genomic RNA
• Diseases
• Medical Cell Biology
• Medical Neurobiology
• Medical Sciences
• Medicine and Health Sciences
• Neurosciences
• Virus Diseases

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/646

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1646