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.
","abstract_html":"<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>","abstract_has_math":false,"creators":["Yang, Zemin"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["J. Paul Taylor, MD, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-06-01T07:00:00Z","date_published":"2023-06-01T07:00:00Z","updated_at":"2026-07-24T05:00:53Z","subjects":["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"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/646","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["J. Paul Taylor, MD, PhD"]},{"key":"dc:creator","label":"Author","values":["Yang, Zemin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-06T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["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"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/646"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["The Interaction Between Host G3BP and Viral Nucleocapsid Protein Regulates SARS-CoV-2 Replication"]}]}],"canonical_facts":{"dc:contributor":["J. Paul Taylor, MD, PhD"],"dc:creator":["Yang, Zemin"],"dc:date.available":["2025-07-06T07:00:00Z"],"dc:description.abstract":["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.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/646"],"dc:subject":["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"],"dc:title":["The Interaction Between Host G3BP and Viral Nucleocapsid Protein Regulates SARS-CoV-2 Replication"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:00:53Z"}