Use of dominant negative mutants of the hepadnaviral core protein as antiviral agents

Paolo Scaglioni, Margherita Melegari, Minoru Takahashi, Jayanta Roy-Chowdhury, Jack Wands

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Chronic hepatitis B virus (HBV) infection is a major cause of acute and chronic liver diseases. We have recently described HBV and woodchuck hepatitis virus (WHV) dominant negative (DN) core mutants that were capable of inhibiting wild-type viral replication by 95%. These mutants may represent a potent class of antiviral agents that act as 'intracellular immunogens.' To facilitate their potential use in animal model systems, we now have studied the duck HBV (DHBV) and placed the DN mutant constructs in recombinant retroviral and adenoviral expression vectors. Transient expression of the DHBV molecular equivalent of the WHV and HBV DN constructs inhibited wild- type DHBV replication by 98%. Recombinant retroviral and adenoviral vectors containing the HBV and DHBV DN complementary DNAs (cDNAs) were used to transiently and stably transduce hepatoma-derived cell lines constitutively expressing replicating wild-type virus. These investigations show that the DN core mutants were powerful inhibitors of HBV and DHBV replication when delivered intracellularly and appear as promising antiviral agents for gene therapy of persistent vital infection of the liver.

Original languageEnglish (US)
Pages (from-to)1010-1017
Number of pages8
JournalHepatology
Volume24
Issue number5
DOIs
StatePublished - Nov 1996

Fingerprint

Duck Hepatitis B Viruses
Woodchuck Hepatitis B Virus
Hepatitis B virus
Antiviral Agents
Ducks
Proteins
Chronic Hepatitis B
Virus Diseases
Genetic Therapy
Liver Diseases
Hepatocellular Carcinoma
Chronic Disease
Animal Models
Complementary DNA
Viruses
Cell Line
Liver
Infection

ASJC Scopus subject areas

  • Hepatology

Cite this

Use of dominant negative mutants of the hepadnaviral core protein as antiviral agents. / Scaglioni, Paolo; Melegari, Margherita; Takahashi, Minoru; Roy-Chowdhury, Jayanta; Wands, Jack.

In: Hepatology, Vol. 24, No. 5, 11.1996, p. 1010-1017.

Research output: Contribution to journalArticle

Scaglioni, Paolo ; Melegari, Margherita ; Takahashi, Minoru ; Roy-Chowdhury, Jayanta ; Wands, Jack. / Use of dominant negative mutants of the hepadnaviral core protein as antiviral agents. In: Hepatology. 1996 ; Vol. 24, No. 5. pp. 1010-1017.
@article{e8f05cd11d6b4d829a9e4c09425e2e41,
title = "Use of dominant negative mutants of the hepadnaviral core protein as antiviral agents",
abstract = "Chronic hepatitis B virus (HBV) infection is a major cause of acute and chronic liver diseases. We have recently described HBV and woodchuck hepatitis virus (WHV) dominant negative (DN) core mutants that were capable of inhibiting wild-type viral replication by 95{\%}. These mutants may represent a potent class of antiviral agents that act as 'intracellular immunogens.' To facilitate their potential use in animal model systems, we now have studied the duck HBV (DHBV) and placed the DN mutant constructs in recombinant retroviral and adenoviral expression vectors. Transient expression of the DHBV molecular equivalent of the WHV and HBV DN constructs inhibited wild- type DHBV replication by 98{\%}. Recombinant retroviral and adenoviral vectors containing the HBV and DHBV DN complementary DNAs (cDNAs) were used to transiently and stably transduce hepatoma-derived cell lines constitutively expressing replicating wild-type virus. These investigations show that the DN core mutants were powerful inhibitors of HBV and DHBV replication when delivered intracellularly and appear as promising antiviral agents for gene therapy of persistent vital infection of the liver.",
author = "Paolo Scaglioni and Margherita Melegari and Minoru Takahashi and Jayanta Roy-Chowdhury and Jack Wands",
year = "1996",
month = "11",
doi = "10.1053/jhep.1996.v24.pm0008903368",
language = "English (US)",
volume = "24",
pages = "1010--1017",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

TY - JOUR

T1 - Use of dominant negative mutants of the hepadnaviral core protein as antiviral agents

AU - Scaglioni, Paolo

AU - Melegari, Margherita

AU - Takahashi, Minoru

AU - Roy-Chowdhury, Jayanta

AU - Wands, Jack

PY - 1996/11

Y1 - 1996/11

N2 - Chronic hepatitis B virus (HBV) infection is a major cause of acute and chronic liver diseases. We have recently described HBV and woodchuck hepatitis virus (WHV) dominant negative (DN) core mutants that were capable of inhibiting wild-type viral replication by 95%. These mutants may represent a potent class of antiviral agents that act as 'intracellular immunogens.' To facilitate their potential use in animal model systems, we now have studied the duck HBV (DHBV) and placed the DN mutant constructs in recombinant retroviral and adenoviral expression vectors. Transient expression of the DHBV molecular equivalent of the WHV and HBV DN constructs inhibited wild- type DHBV replication by 98%. Recombinant retroviral and adenoviral vectors containing the HBV and DHBV DN complementary DNAs (cDNAs) were used to transiently and stably transduce hepatoma-derived cell lines constitutively expressing replicating wild-type virus. These investigations show that the DN core mutants were powerful inhibitors of HBV and DHBV replication when delivered intracellularly and appear as promising antiviral agents for gene therapy of persistent vital infection of the liver.

AB - Chronic hepatitis B virus (HBV) infection is a major cause of acute and chronic liver diseases. We have recently described HBV and woodchuck hepatitis virus (WHV) dominant negative (DN) core mutants that were capable of inhibiting wild-type viral replication by 95%. These mutants may represent a potent class of antiviral agents that act as 'intracellular immunogens.' To facilitate their potential use in animal model systems, we now have studied the duck HBV (DHBV) and placed the DN mutant constructs in recombinant retroviral and adenoviral expression vectors. Transient expression of the DHBV molecular equivalent of the WHV and HBV DN constructs inhibited wild- type DHBV replication by 98%. Recombinant retroviral and adenoviral vectors containing the HBV and DHBV DN complementary DNAs (cDNAs) were used to transiently and stably transduce hepatoma-derived cell lines constitutively expressing replicating wild-type virus. These investigations show that the DN core mutants were powerful inhibitors of HBV and DHBV replication when delivered intracellularly and appear as promising antiviral agents for gene therapy of persistent vital infection of the liver.

UR - http://www.scopus.com/inward/record.url?scp=0029953004&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029953004&partnerID=8YFLogxK

U2 - 10.1053/jhep.1996.v24.pm0008903368

DO - 10.1053/jhep.1996.v24.pm0008903368

M3 - Article

VL - 24

SP - 1010

EP - 1017

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 5

ER -