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 journalArticlepeer-review

66 Scopus citations

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

ASJC Scopus subject areas

  • Hepatology

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