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Poly(rC)-Binding Protein 1 Limits Hepatitis C Virus Virion Assembly and Secretion
The hepatitis C virus (HCV) co-opts numerous cellular elements, including proteins, lipids, and microRNAs, to complete its viral life cycle. The cellular RNA-binding protein, poly(rC)-binding protein 1 (PCBP1), was previously reported to bind to the 5′ untranslated region (UTR) of the HCV genome; ho...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877974/ https://www.ncbi.nlm.nih.gov/pubmed/35215884 http://dx.doi.org/10.3390/v14020291 |
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author | Cousineau, Sophie E. Rheault, Marylin Sagan, Selena M. |
author_facet | Cousineau, Sophie E. Rheault, Marylin Sagan, Selena M. |
author_sort | Cousineau, Sophie E. |
collection | PubMed |
description | The hepatitis C virus (HCV) co-opts numerous cellular elements, including proteins, lipids, and microRNAs, to complete its viral life cycle. The cellular RNA-binding protein, poly(rC)-binding protein 1 (PCBP1), was previously reported to bind to the 5′ untranslated region (UTR) of the HCV genome; however, its importance in the viral life cycle has remained unclear. Herein, we sought to clarify the role of PCBP1 in the HCV life cycle. Using the HCV cell culture (HCVcc) system, we found that knockdown of endogenous PCBP1 resulted in an overall decrease in viral RNA accumulation, yet resulted in an increase in extracellular viral titers. To dissect PCBP1’s specific role in the HCV life cycle, we carried out assays for viral entry, translation, genome stability, RNA replication, as well as virion assembly and secretion. We found that PCBP1 knockdown did not directly affect viral entry, translation, RNA stability, or RNA replication, but resulted in an overall increase in infectious particle secretion. This increase in virion secretion was evident even when viral RNA synthesis was inhibited, and blocking virus secretion could partially restore the viral RNA accumulation decreased by PCBP1 knockdown. We therefore propose a model where endogenous PCBP1 normally limits virion assembly and secretion, which increases viral RNA accumulation in infected cells by preventing the departure of viral genomes packaged into virions. Overall, our findings improve our understanding of how cellular RNA-binding proteins influence viral genomic RNA utilization during the HCV life cycle. |
format | Online Article Text |
id | pubmed-8877974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88779742022-02-26 Poly(rC)-Binding Protein 1 Limits Hepatitis C Virus Virion Assembly and Secretion Cousineau, Sophie E. Rheault, Marylin Sagan, Selena M. Viruses Article The hepatitis C virus (HCV) co-opts numerous cellular elements, including proteins, lipids, and microRNAs, to complete its viral life cycle. The cellular RNA-binding protein, poly(rC)-binding protein 1 (PCBP1), was previously reported to bind to the 5′ untranslated region (UTR) of the HCV genome; however, its importance in the viral life cycle has remained unclear. Herein, we sought to clarify the role of PCBP1 in the HCV life cycle. Using the HCV cell culture (HCVcc) system, we found that knockdown of endogenous PCBP1 resulted in an overall decrease in viral RNA accumulation, yet resulted in an increase in extracellular viral titers. To dissect PCBP1’s specific role in the HCV life cycle, we carried out assays for viral entry, translation, genome stability, RNA replication, as well as virion assembly and secretion. We found that PCBP1 knockdown did not directly affect viral entry, translation, RNA stability, or RNA replication, but resulted in an overall increase in infectious particle secretion. This increase in virion secretion was evident even when viral RNA synthesis was inhibited, and blocking virus secretion could partially restore the viral RNA accumulation decreased by PCBP1 knockdown. We therefore propose a model where endogenous PCBP1 normally limits virion assembly and secretion, which increases viral RNA accumulation in infected cells by preventing the departure of viral genomes packaged into virions. Overall, our findings improve our understanding of how cellular RNA-binding proteins influence viral genomic RNA utilization during the HCV life cycle. MDPI 2022-01-29 /pmc/articles/PMC8877974/ /pubmed/35215884 http://dx.doi.org/10.3390/v14020291 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cousineau, Sophie E. Rheault, Marylin Sagan, Selena M. Poly(rC)-Binding Protein 1 Limits Hepatitis C Virus Virion Assembly and Secretion |
title | Poly(rC)-Binding Protein 1 Limits Hepatitis C Virus Virion Assembly and Secretion |
title_full | Poly(rC)-Binding Protein 1 Limits Hepatitis C Virus Virion Assembly and Secretion |
title_fullStr | Poly(rC)-Binding Protein 1 Limits Hepatitis C Virus Virion Assembly and Secretion |
title_full_unstemmed | Poly(rC)-Binding Protein 1 Limits Hepatitis C Virus Virion Assembly and Secretion |
title_short | Poly(rC)-Binding Protein 1 Limits Hepatitis C Virus Virion Assembly and Secretion |
title_sort | poly(rc)-binding protein 1 limits hepatitis c virus virion assembly and secretion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877974/ https://www.ncbi.nlm.nih.gov/pubmed/35215884 http://dx.doi.org/10.3390/v14020291 |
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