Interferon gene transfer by a hepatitis B virus vector efficiently suppresses wild-type virus infection.
Hepatitis B viruses specifically target the liver, where they efficiently infect quiescent hepatocytes. Here we show that human and avian hepatitis B viruses can be converted into vectors for liver-directed gene transfer. These vectors allow hepatocyte-specific expression of a green fluorescent protein in vitro and in vivo. Moreover, when used to transduce a type I interferon gene, expression of interferon efficiently suppresses wild-type virus replication in the duck model of hepatitis B virus infection. These data suggest local cytokine production after hepatitis-B-virus-mediated gene transfer as a promising concept for the treatment of acquired liver diseases, including chronic hepatitis B.
Protzer
U
U
Zentrum für Molekulare Biologie Heidelberg, University of Heidelberg, Im Neuenheimer Feld, D-69120 Heidelberg, Germany.
Nassal
M
M
Chiang
P W
PW
Kirschfink
M
M
Schaller
H
H
D000818:Animals; D002478:Cells, Cultured; D004372:Ducks; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006509:Hepatitis B / Q000517:prevention & control; D015611:Hepatitis B Virus, Duck / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007372:Interferons / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D010957:Plasmids / Q000378:metabolism; D013997:Time Factors
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D007372:Interferons