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 - Chowdhury, Jayanta Roy
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.
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U2 - 10.1053/jhep.1996.v24.pm0008903368
DO - 10.1053/jhep.1996.v24.pm0008903368
M3 - Article
C2 - 8903368
AN - SCOPUS:0029953004
SN - 0270-9139
VL - 24
SP - 1010
EP - 1017
JO - Hepatology
JF - Hepatology
IS - 5
ER -