TY - JOUR
T1 - Characterization of antiviral activity of lactoferrin against hepatitis C virus infection in human cultured cells
AU - Ikeda, Masanori
AU - Nozaki, Akito
AU - Sugiyama, Kazuo
AU - Tanaka, Torahiko
AU - Naganuma, Atsushi
AU - Tanaka, Katsuaki
AU - Sekihara, Hisahiko
AU - Shimotohno, Kunitada
AU - Saito, Masaki
AU - Kato, Nobuyuki
N1 - Funding Information:
We are grateful to T. Mizutani (Graduate School of Veterinary Medicine, Hokkaido University), K. Sekine and H. Tsuda (Chemotherapy Division, National Cancer Center Research Institute) for helpful suggestions and discussion. M.I. is a recipient of Postdoctoral Fellowship from Drug ADR Relief, R&D Promotion and Product Review of Japan. Two A.N. are recipients of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research, Japan. This work was supported by grants from Grants-in-Aid for Cancer Research and for the Second-Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare, and Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, and the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Drug ADR Relief, R&D Promotion and Product Review of Japan.
PY - 2000/1
Y1 - 2000/1
N2 - We recently found that bovine lactoferrin (bLF), a milk glycoprotein belonging to the iron transporter family, prevented hepatitis C virus (HCV) infection in human hepatocyte PH5CH8 cells, that are susceptible to HCV infection, and demonstrated that the anti-HCV activity of bLF was due to the interaction of bLF and HCV. In this study we further characterized the anti- HCV activity of bLF and the mechanism by which bLF prevents HCV infection. We found that bLF inhibited viral entry to the cells by interacting directly with HCV immediately after mixing of bLF and HCV inoculum. The anti-HCV activity of bLF was lost by heating at 65°C, and other milk proteins (mucin, β-lactoglobulin and casein) did not prevent HCV infection, indicating that bLF prevented HCV infection in a rather specific manner. Furthermore, we found that bovine lactoferricin, a basic N-terminal loop of bLF that is an important region for antibacterial activity, did not exhibit any anti-HCV activity, suggesting that some other region is involved in anti-HCV activity. We confirmed that prevention of HCV infection by bLF was a general phenomenon, because bLF inhibited HCV infection with all five inocula examined, and bLF inhibited HCV infection in human MT-2C T-cells, that were susceptible to HCV infection. In addition, infection with hepatitis G virus, which is distantly related to HCV, was prevented also by bLF. In conclusion, lactoferrin is a natural glycoprotein which effectively protects against HCV infection in hepatocytes and lymphocytes by neutralizing the virus. (C) 2000 Elsevier Science B.V.
AB - We recently found that bovine lactoferrin (bLF), a milk glycoprotein belonging to the iron transporter family, prevented hepatitis C virus (HCV) infection in human hepatocyte PH5CH8 cells, that are susceptible to HCV infection, and demonstrated that the anti-HCV activity of bLF was due to the interaction of bLF and HCV. In this study we further characterized the anti- HCV activity of bLF and the mechanism by which bLF prevents HCV infection. We found that bLF inhibited viral entry to the cells by interacting directly with HCV immediately after mixing of bLF and HCV inoculum. The anti-HCV activity of bLF was lost by heating at 65°C, and other milk proteins (mucin, β-lactoglobulin and casein) did not prevent HCV infection, indicating that bLF prevented HCV infection in a rather specific manner. Furthermore, we found that bovine lactoferricin, a basic N-terminal loop of bLF that is an important region for antibacterial activity, did not exhibit any anti-HCV activity, suggesting that some other region is involved in anti-HCV activity. We confirmed that prevention of HCV infection by bLF was a general phenomenon, because bLF inhibited HCV infection with all five inocula examined, and bLF inhibited HCV infection in human MT-2C T-cells, that were susceptible to HCV infection. In addition, infection with hepatitis G virus, which is distantly related to HCV, was prevented also by bLF. In conclusion, lactoferrin is a natural glycoprotein which effectively protects against HCV infection in hepatocytes and lymphocytes by neutralizing the virus. (C) 2000 Elsevier Science B.V.
KW - Bovine lactoferrin
KW - Hepatitis C virus
KW - Hepatitis G virus
KW - MT-2C cells
KW - PH5CH8 cells
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U2 - 10.1016/S0168-1702(99)00121-5
DO - 10.1016/S0168-1702(99)00121-5
M3 - Article
C2 - 10653917
AN - SCOPUS:0033956354
VL - 66
SP - 51
EP - 63
JO - Virus Research
JF - Virus Research
SN - 0168-1702
IS - 1
ER -