Homology between HBV-DNA and a sequence regulating the interferon-induced antiviral system: possible mechanism of persistent infection.

Treatment of hepatitis B virus (HBV)-infected hepatocytes with lymphoblastoid alpha-interferon (IFN) leads to an increased expression of the core antigen (HBcAg) and reduced expression of surface antigen (HBsAg). We have identified the presence of a nucleotide sequence at the start of the HBc gene in the hepatitis B virus genome similar to a consensus sequence known to occur upstream from genes induced by IFN in mammalian cells. It is possible that interferon influences the expression of the viral genes because of the presence of this homologous sequence. This sequence in the viral genome may determine the site of integration of the virus and could influence the ability of the cell containing the integrated viral sequence to respond to interferon. This "neutralisation" of the interferon system by viral integration might not only facilitate persistent infection but might also adversely affect response to alpha-interferon therapy.