Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Cousineau, Sophie E., Rheault, Marylin, Sagan, Selena M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784658542853095424
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
work_keys_str_mv AT cousineausophiee polyrcbindingprotein1limitshepatitiscvirusvirionassemblyandsecretion
AT rheaultmarylin polyrcbindingprotein1limitshepatitiscvirusvirionassemblyandsecretion
AT saganselenam polyrcbindingprotein1limitshepatitiscvirusvirionassemblyandsecretion