ABSTRACT

Lactoferrin (LF), which is a milk protein belonging to the iron transporter family, is known to be a primary defense protein against pathogenic microorganisms. Recently, several groups have reported that human and/or bovine LF has inhibitory activity against pathogenic viruses including human herpes simplex virus-1, human cytomegalovirus, human immunodeficiency virus-1 and simian rotavirus, although the inhibitory mechanisms have not been clarified. Recently, we also found that both human and bovine LFs effectively and specifically prevented hepatitis C virus (HCV) infection in cultured human hepatocytes, which were susceptible to HCV infection and supported HCV replication. The HCV inhibitory activity of LF was found to be due to a direct interaction between LF and HCV. In addition, infection with hepatitis G virus, which is distantly related to HCV, was also prevented by LF. Further in vitro analysis using recombinant proteins demonstrated a direct interaction between LF and HCV E2 envelope protein, and identified the binding regions of LF. In clinical trials of LF in patients with chronic hepatitis C, some patients receiving LF showed improvement of hepatitis and a decrease in serum HCV RNA levels. The possible application of LF for further clinical therapy is discussed.