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

Ikeda, Masanori; Nozaki, Akito; Sugiyama, Kazuo; Tanaka, Torahiko; Naganuma, Atsushi; Tanaka, Katsuaki; Sekihara, Hisahiko; Shimotohno, Kunitada; Saito, Masaki; Kato, Naoya

doi:10.1016/s0168-1702(99)00121-5

Cited by 132 publications

(118 citation statements)

References 39 publications

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“…This is consistent with the findings of Ikeda et al (2000) who reported that while lactoferrin displayed anti-HCV activity, lactoferricin B displayed no anti-HCV activity. In addition, Yi et al (1997) reported that both intact lactoferrin and lactoferrin devoid of the N-terminal, bactericidal domain (encompassing the lactoferricin B sequence), bound to HCV envelope proteins, suggesting that this domain was not essential for the binding and antiviral activity of lactoferrin against HCV.…”

Section: Discussionsupporting

confidence: 93%

The effect of bovine lactoferrin and lactoferricin B on the ability of feline calicivirus (a norovirus surrogate) and poliovirus to infect cell cultures

et al. 2003

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Aims:To characterize the effect of bovine lactoferrin and lactoferricin B against feline calicivirus (FCV), a norovirus surrogate and poliovirus (PV), as models for enteric viruses. Methods and Results: Crandell-Reese feline kidney (CRFK) cells were used for the propagation of FCV and monkey embryo kidney (MEK) cells for PV. The assays included visual assessment of cell lines for cytopathic effects and determination of the percentage cell death using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium] dye reduction assay. Incubation of bovine lactoferrin with CRFK cells either prior to or together with FCV inoculation substantially reduced FCV infection. In contrast, the interference of lactoferrin with the infection of cells with PV was demonstrated only when lactoferrin was present with cell lines and virus for the entire assay period. Using indirect immunofluorescence, lactoferrin was detected on the surface of both CRFK and MEK cells, suggesting that the interference of viral infection may be attributed to lactoferrin binding to the surfaces of susceptible cells, thereby preventing the attachment of the virus particles. Lactoferricin B, a cationic antimicrobial peptide derived from the N-terminal domain of bovine lactoferrin, reduced FCV but not PV infection. Conclusion: Lactoferrin was shown to interfere with the infection of cells for both FCV and PV. However, lactoferricin B showed no interference of infection with PV and interference with infection for FCV required the presence of lactoferricin B together with the cell line and virus. Significance and Impact of the Study: An in vitro basis is provided for the effects of bovine lactoferrin and lactoferricin B in moderating food-borne infections of enteric viruses.

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Section: Discussionsupporting

confidence: 93%

The effect of bovine lactoferrin and lactoferricin B on the ability of feline calicivirus (a norovirus surrogate) and poliovirus to infect cell cultures

et al. 2003

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“…Bactericidal (Bellamy et al, 1992;Zagulski et al, 1998), anti-inflammatory (Nuijens et al, 1996), antiviral (Swart et al, 1998;Ikeda et al, 2000;Murphy et al, 2000) and antioxidative activities (Gutteridge et al, 1981;Baldwin et al, 1984;Davidson & Lonnerdal, 1989) were discovered previously. Concomitant ingestion of lactoferrin together with indomethacin may protect against indomethacin-induced gastroenteropathy.…”

Section: Introductionmentioning

confidence: 98%

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

2003

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Objective: To determine whether recombinant human lactoferrin ingestion inhibits nonsteroidal antiinflammatory drugs (NSAID)-induced gastroenteropathy in vivo in healthy volunteers as a model for disorders associated with a rise in permeability of the stomach and the small intestine. Design: A randomized crossover dietary intervention. Subjects and interventions: In all, 15 healthy volunteers (age 2371.4 y) were tested. A sucrose and a lactulose/rhamnose (L/R) permeability test was performed to assess gastroduodenal and small intestine permeability as indicator of NSAID-induced gastroenteropathy. All subjects consumed standardized meals for 2 days. On the second day at time ¼ À24 h each subject ingested a drink containing 5 g recombinant human lactoferrin or placebo during breakfast. At t ¼ À9 h, subjects ingested the same drink with 75 mg of the NSAID indomethacin and after an overnight fast at t ¼ À1 h subjects consumed the drink and 50 mg indomethacin. After 1 h, at t ¼ 0, a permeability test was performed. Results: Small intestine permeability after indomethacin and placebo was significantly higher (L/R ratio ¼ 0.036; 0.014-0.092, Po0.05) compared to the permeability observed after ingestion of indomethacin and lactoferrin (0.028; 0.015-0.056), whereas gastroduodenal permeability did not differ between the two interventions (P ¼ 0.3). Conclusion: Oral recombinant human lactoferrin supplementation during a short-term indomethacin challenge reduced the NSAID-mediated increase in small intestinal permeability and hence may provide a nutritional tool in the treatment of hyperpermeability-associated disorders. Sponshorship: Grant and human recombinant lactoferrin donated from Agennix Inc., Houston, TX.

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“…Therefore, LF is postulated to be involved in the innate host defense against infection and severe inflammation, most notable at mucosal surfaces such as those of the gastrointestinal tract (33). Antimicrobial properties of LF include bacteriostasis by iron deprivation (34), bactericidal activity by destabilization of the cell wall (7,10), and antiviral activity by inhibition of viral infection (35). Besides antimicrobial activity, LF has been shown to promote the growth of Bifidobacterium species, the predominant bacteria of the intestinal flora of healthy breast-fed newborns (36).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Porcine Lactoferrin Expressed in the Milk of Transgenic Mice Enhances Offspring Growth Performance

Chen

Yen

et al. 2007

J. Agric. Food Chem.

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The European Commission has proposed a permanent ban on the use of antibiotics as an ingredient in animal feed to promote growth. Lactoferrin is a globular multifunctional protein that has been shown to play a role in iron absorption and to have antimicrobial and anti-inflammatory activities. Therefore, lactoferrin may serve as a nontherapeutic alternative to antibiotics in livestock husbandry. As a pilot study toward this goal, transgenic mice have been generated harboring a porcine lactoferrin (pLF) gene driven by the mammary gland-specific promoter of the bovine R-lactalbumin (RLA) gene. The RLA-pLF hybrid gene was confirmed to have been successfully integrated and transmitted stably through the germ-line in 9 (5 females and 4 males) of 14 transgenic founders. In the female progenies of six lines analyzed, the transgene copy numbers ranged from 1 to 20 with 1-4 integration sites. Significant levels of pLF protein in milk ranging from 40 to 106 µg/mL with physical characteristics similar to those of native pLF in sow's milk were achieved in three of the transgenic lines obtained. Tissue-and stage-specific pLF expressions were restricted to the mammary gland of the transgenic female mice during lactation. It was further demonstrated that the growth performance of animal pups is enhanced by directly feeding the genetically engineered milk containing enriched pLF protein in transgenic mice. Furthermore, this enhanced growth performance in suckling mice was proportional to the concentration of pLF present in milk.

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

Cited by 132 publications

References 39 publications

The effect of bovine lactoferrin and lactoferricin B on the ability of feline calicivirus (a norovirus surrogate) and poliovirus to infect cell cultures

The effect of bovine lactoferrin and lactoferricin B on the ability of feline calicivirus (a norovirus surrogate) and poliovirus to infect cell cultures

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers

Recombinant Porcine Lactoferrin Expressed in the Milk of Transgenic Mice Enhances Offspring Growth Performance

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