Characterization of antiviral activity of lactoferrin against hepatitis C virus infection in human cultured cells

We recently found that bovine lactoferrin (bLF), a milk glycoprotein belong ing to the iron transporter family, prevented hepatitis C virus (HCV) infec tion in human hepatocyte PH5CH8 cells, that are susceptible to HCV infectio n, and demonstrated that the anti-HCV activity of bLF was due to the intera ction of bLF and HCV. In this study we further characterized the anti-HCV a ctivity of bLF and the mechanism by which bLF prevents HCV infection. We fo und that bLF inhibited viral entry to the cells by interacting directly wit h HCV immediately after mixing of bLF and HCV inoculum. The anti-HCV activi ty of bLF was lost by heating at 65 degrees C, and other milk proteins (muc in, beta-lactoglobulin and casein) did not prevent HCV infection, indicatin g that bLF prevented HCV infection in a rather specific manner. Furthermore , we found that bovine lactoferricin, a basic N-terminal loop of bLF that i s an important region for antibacterial activity, did not exhibit any anti- HCV activity, suggesting that some other region is involved in anti-HCV act ivity. We confirmed that prevention of HCV infection by bLF was a general p henomenon, because bLF inhibited HCV infection with all five inocula examin ed, and bLF inhibited HCV infection in human MT-2C T-cells, that were susce ptible to HCV infection. In addition, infection with hepatitis G virus, whi ch is distantly related to HCV, was prevented also by bLF. In conclusion, l actoferrin is a natural glycoprotein which effectively protects against HCV infection in hepatocytes and lymphocytes by neutralizing the virus. (C) 20 00 Elsevier Science B.V. All rights reserved.