Differential effect of p7 inhibitors on hepatitis C virus cell-to-cell transmission

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Differential effect of p7 inhibitors on hepatitis C virus cell-to-cell transmission. / Meredith, L.w.; Zitzmann, N.; McKeating, Jane.

In: Antiviral Research, Vol. 100, No. 3, 01.12.2013, p. 636-639.

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@article{74220b60d1704756a2f205086e0b5075,
title = "Differential effect of p7 inhibitors on hepatitis C virus cell-to-cell transmission",
abstract = "Inhibitors targeting the hepatitis C virus (HCV) encoded viroporin, p7 prevent virus release in vitro. HCV can transmit by cell-free particle infection of new target cells and via cell-to-cell dependent contact with limited exposure to the extracellular environment. The role of assembly inhibitors in preventing HCV transmission via these pathways has not been studied. We compared the efficacy of three published p7 inhibitors to inhibit cell-free and cell-to-cell transmission of two chimeric HCV strains encoding genotype 2 (GT2) or 5 (GT5) p7 using a recently developed single cycle co-culture assay. The inhibitors reduced the infectivity of extracellular GT2 and GT5 virus by 80–90% and GT2 virus cell-to-cell transmission by 50%. However, all of the p7 inhibitors had minimal effect on GT5 cell contact dependent transmission. Screening a wider panel of diverse viral genotypes demonstrated that p7 viroporin inhibitors were significantly more effective at blocking cell-free virus than cell-to-cell transmission. These results suggest an altered assembly or trafficking of cell-to-cell transmitted compared to secreted virus. These observations have important implications for the validation, therapeutic design and testing of HCV assembly inhibitors.",
keywords = "p7, Hepatitis C, Assembly, Inhibitors, Cell-to-cell",
author = "L.w. Meredith and N. Zitzmann and Jane McKeating",
year = "2013",
month = dec
day = "1",
doi = "10.1016/j.antiviral.2013.10.006",
language = "English",
volume = "100",
pages = "636--639",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Differential effect of p7 inhibitors on hepatitis C virus cell-to-cell transmission

AU - Meredith, L.w.

AU - Zitzmann, N.

AU - McKeating, Jane

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Inhibitors targeting the hepatitis C virus (HCV) encoded viroporin, p7 prevent virus release in vitro. HCV can transmit by cell-free particle infection of new target cells and via cell-to-cell dependent contact with limited exposure to the extracellular environment. The role of assembly inhibitors in preventing HCV transmission via these pathways has not been studied. We compared the efficacy of three published p7 inhibitors to inhibit cell-free and cell-to-cell transmission of two chimeric HCV strains encoding genotype 2 (GT2) or 5 (GT5) p7 using a recently developed single cycle co-culture assay. The inhibitors reduced the infectivity of extracellular GT2 and GT5 virus by 80–90% and GT2 virus cell-to-cell transmission by 50%. However, all of the p7 inhibitors had minimal effect on GT5 cell contact dependent transmission. Screening a wider panel of diverse viral genotypes demonstrated that p7 viroporin inhibitors were significantly more effective at blocking cell-free virus than cell-to-cell transmission. These results suggest an altered assembly or trafficking of cell-to-cell transmitted compared to secreted virus. These observations have important implications for the validation, therapeutic design and testing of HCV assembly inhibitors.

AB - Inhibitors targeting the hepatitis C virus (HCV) encoded viroporin, p7 prevent virus release in vitro. HCV can transmit by cell-free particle infection of new target cells and via cell-to-cell dependent contact with limited exposure to the extracellular environment. The role of assembly inhibitors in preventing HCV transmission via these pathways has not been studied. We compared the efficacy of three published p7 inhibitors to inhibit cell-free and cell-to-cell transmission of two chimeric HCV strains encoding genotype 2 (GT2) or 5 (GT5) p7 using a recently developed single cycle co-culture assay. The inhibitors reduced the infectivity of extracellular GT2 and GT5 virus by 80–90% and GT2 virus cell-to-cell transmission by 50%. However, all of the p7 inhibitors had minimal effect on GT5 cell contact dependent transmission. Screening a wider panel of diverse viral genotypes demonstrated that p7 viroporin inhibitors were significantly more effective at blocking cell-free virus than cell-to-cell transmission. These results suggest an altered assembly or trafficking of cell-to-cell transmitted compared to secreted virus. These observations have important implications for the validation, therapeutic design and testing of HCV assembly inhibitors.

KW - p7

KW - Hepatitis C

KW - Assembly

KW - Inhibitors

KW - Cell-to-cell

U2 - 10.1016/j.antiviral.2013.10.006

DO - 10.1016/j.antiviral.2013.10.006

M3 - Article

C2 - 24157306

VL - 100

SP - 636

EP - 639

JO - Antiviral Research

JF - Antiviral Research

SN - 0166-3542

IS - 3

ER -