Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.

Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Fei Xiao, Isabel Fofana, Laura Heydmann, Heidi Barth, Eric Soulier, François Habersetzer, Michel Doffoël, Jens Bukh, Arvind H Patel, Mirjam B Zeisel, Thomas F Baumert
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3d82659e652242da9ba2435e2b6c3d43
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3d82659e652242da9ba2435e2b6c3d43
record_format	dspace
spelling	oai:doaj.org-article:3d82659e652242da9ba2435e2b6c3d432021-11-18T06:06:35ZHepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.1553-73661553-737410.1371/journal.ppat.1004128https://doaj.org/article/3d82659e652242da9ba2435e2b6c3d432014-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24830295/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs.Fei XiaoIsabel FofanaLaura HeydmannHeidi BarthEric SoulierFrançois HabersetzerMichel DoffoëlJens BukhArvind H PatelMirjam B ZeiselThomas F BaumertPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 5, p e1004128 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Fei Xiao Isabel Fofana Laura Heydmann Heidi Barth Eric Soulier François Habersetzer Michel Doffoël Jens Bukh Arvind H Patel Mirjam B Zeisel Thomas F Baumert Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.
description	Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs.
format	article
author	Fei Xiao Isabel Fofana Laura Heydmann Heidi Barth Eric Soulier François Habersetzer Michel Doffoël Jens Bukh Arvind H Patel Mirjam B Zeisel Thomas F Baumert
author_facet	Fei Xiao Isabel Fofana Laura Heydmann Heidi Barth Eric Soulier François Habersetzer Michel Doffoël Jens Bukh Arvind H Patel Mirjam B Zeisel Thomas F Baumert
author_sort	Fei Xiao
title	Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.
title_short	Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.
title_full	Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.
title_fullStr	Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.
title_full_unstemmed	Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.
title_sort	hepatitis c virus cell-cell transmission and resistance to direct-acting antiviral agents.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/3d82659e652242da9ba2435e2b6c3d43
work_keys_str_mv	AT feixiao hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents AT isabelfofana hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents AT lauraheydmann hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents AT heidibarth hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents AT ericsoulier hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents AT francoishabersetzer hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents AT micheldoffoel hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents AT jensbukh hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents AT arvindhpatel hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents AT mirjambzeisel hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents AT thomasfbaumert hepatitiscviruscellcelltransmissionandresistancetodirectactingantiviralagents
_version_	1718424530494423040

Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents.

Ejemplares similares