Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus

Ammendolia, Maria Grazia; Agamennone, Mariangela; Pietrantoni, Agostina; Lannutti, F; Siciliano, Rosa Anna; Giulio, Beatrice De; Amici, Carla; Superti, Fabiana

doi:10.1179/2047773212y.0000000004

Cited by 55 publications

(61 citation statements)

References 49 publications

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“…Bovine lactoferrin (bLF) inhibits the viral entry into hepatocytes and lymphocytes via neutralizing the virion and blocking the invasion of the cell, but showed no antiviral activity after HCV internalization into the cells [92]. However, N-lobe of camel lactoferrin mostly exerts its action on HCV through the intracellular pathway, therefore supporting the hypothesis that antiviral activity of LF depend on the virus type, protein structure, and bioassay system used [92,93]. In line with this view, camel lactoferrin and its C-lobe showed weaker potency than N-lobe in the case of the HCV infection, whereas the inhibition of influenza virus heagglutination and cell infection of all major influenza virus subtypes were entirely attributed to the C-lobe of bovine lactoferrin only [94].…”

Section: Discussionmentioning

confidence: 93%

Screening the anti infectivity potentials of native N- and C-lobes derived from the camel lactoferrin against hepatitis C virus

Redwan

El‐Fakharany

Uversky

et al. 2014

BMC Complement Altern Med

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BackgroundHepatitis C virus (HCV) infection represents a worldwide health threat that still needs efficient protective vaccine and/or effective drug. The traditional medicine, such as camel milk, is heavily used by the large sector of HCV patients to control the infection due to the high cost of the available standard therapy. Camel milk contains lactoferrin, which plays an important and multifunctional role in innate immunity and specific host defense against microbial infection. Continuing the analysis of the effectiveness of camel lactoferrin against HCV, the current study aimed to separate and purify the native N- and C-lobes from the proteolytically cleaved camel lactoferrin (cLF) and to compare their in vitro activities against the HCV infection in Huh7.5 cells in order to determine the most active domain.MethodsLactoferrin and its digested N- and C-lobes were purified by Mono S 5/50 GL column and Superdex 200 5/150 column. The purified proteins were assessed through three venues: 1. To inhibit intracellular replication, HCV infected cells were treated with the proteins at different concentrations and time intervals; 2. The proteins were directly incubated with the viral particles (neutralization) and then such neutralized viruses were used to infect cells; 3. The cells were protected with proteins before exposure to the virus. The antiviral potentials of the cLf and its lobes were determined using three techniques: 1. RT-nested PCR, 2. Real-time PCR, and 3. Flow cytometry.ResultsN- and C-lobes were purified in two consecutive steps; using Mono-S and Superdex 200 columns. The molecular mass of N- and C-lobes was about 40 kDa. cLF and its lobes could prevent HCV entry into Huh 7.5 cells with activity reached 100% through direct interaction with the virus. The inhibition of intracellular viral replication by N-lobe is 2-fold and 3-fold more effective than that of the cLF and C-lobe, respectively.ConclusionGenerated native N- and C-lobes from camel lactoferrin demonstrated a range of noticeably different potentials against HCV cellular infectivity. The anti-HCV activities were sorted as N-lobe > cLf > C-lobe.

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Section: Discussionmentioning

confidence: 93%

Screening the anti infectivity potentials of native N- and C-lobes derived from the camel lactoferrin against hepatitis C virus

Redwan

El‐Fakharany

Uversky

et al. 2014

BMC Complement Altern Med

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“…[67] Citation: Luna-Castro S, Samaniego-Barrón L, Serrano-Rubio LE, Ceballos-Olvera I, Avalos-Gómez C, et al -bLf-derived peptides were better inhibitors than the entire protein. The inhibition of replication in bovine herpesvirus 1 by bLf has been demonstrated; this is an alphaherpesvirus responsible for abortion, infertility, genital disease, and respiratory infection in cattle.…”

Section: In Vitro Assaysmentioning

confidence: 99%

“…The inhibition of influenza virus haemagglutination was demonstrated, and cell infection is entirely attributed to the bLf C-lobe. By far-Western blotting and sequencing, the strong binding of the bLf C-lobe to the HA2 region of viral HA has been well demonstrated, and three C-lobe fragments of bLf have been identified as virus haemagglutination and infection inhibitors at femtomolar concentrations [67].…”

Section: In Vitro Assaysmentioning

confidence: 99%

Lactoferrin: A Powerful Antimicrobial Protein Present in Milk

Luna-Castro¹,

Samaniego-Barrón²,

Serrano-Rubio³

et al. 2017

J Adv Dairy Res

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Lactoferrin (Lf) is an iron-chelating glycoprotein present in milk and mucosal secretions, a component of the mammalian innate immune system. Lf is microbiostatic and microbicidal. Lf can reduce the bacterial expression of virulence factors, such as those involved in biofilm production and protease secretion. The high identity among mammalian Lf sequences facilitates its use in human and veterinary medicine. Lf of bovine origin is the principal Lf used due to its commercial availability through purification from milk whey; recombinant Lfs (bovine, human, and porcine) have been used as well. Lf is a stable protein that retains its physicochemical characteristics under gastric pH conditions, and in most cases it is bioactive even after digestion; thus, the incorporation of Lf into diets facilitates its administration to animals. The aim of this review is to examine original research in which the effects of bovine and porcine Lf on pathogens of domestic animals have been demonstrated through in vitro and in vivo assays, with the purpose of ascertaining the benefits that Lf provides in the treatment of infectious diseases.

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“…It was recently suggested that Lf is closely related to therapeutics (Ammendolia et al, 2012;Kido et al, 2012;Ordaz-Pichardo et al, 2012;Paesano et al, 2012), and it improved some physiological and immunological parameters (Eslamloo et al, 2012;Liao et al, 2012;Langhorst and Boone, 2012). In malignant mammary epithelial cells, Lf has been suggested to have antiproliferative effects to protect from local and distant metastasis, and downregulated Lf expression has been reported in breast cancer (Campbell et al, 1992;Benaïssa et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Paesano et al (2012) provided strong evidence for a role of Lf in preterm delivery treatment, thus extending the therapeutic potential of this multifunctional natural protein. Besides explaining the broad anti-influenza activity of Lf, Ammendolia et al (2012) lay the foundations for exploiting Lf fragments as a source of potential anti-influenza therapeutics. Ordaz-Pichardo et al (2012) suggested that Lf may aid in the therapy of amoebiasis, likely without producing undesirable effects in patients.…”

Section: Introductionmentioning

confidence: 99%

Lactoferrin mRNA expression in mouse mammary glands during pregnancy and lactation

Li¹,

Jiao²,

Wang³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Lactoferrin (Lf) is an iron-binding glycoprotein that is produced by mucosal epithelial cells in mammals. Lf has non-immune natural defense functions and biological functions in addition to and distinct from its role in regulating inflammatory responses. Lf also improved some physiological and immunological parameters. Lf is a biomarker for monitoring medical treatment in inflammatory bowel diseases. Current LF research focuses on iron absorption, antimicrobial activity, and the modulation of iron metabolism during inflammation.No systematic research about Lf expression levels in mouse mammary glands during pregnancy and lactation exists. We investigated Lf mRNA expression levels in mouse mammary glands by collecting samples on days 1, 6, 12, and 18 of pregnancy and lactation (six mice per group). The expression levels of Lf mRNA were measured by semi-quantitative reverse transcription polymerase chain reaction using GAPDH as an internal control. Lf mRNA was not expressed in mammary glands on days 1, 6, and 12 of pregnancy, but it was expressed on day 18 (IOD: integrated optical density; Lf IOD /GAPDH IOD = 0.46). Lf expression levels were higher during lactation stages than during pregnancy stages, and it stabilized at 0.71-0.73 (Lf IOD /GAPDH IOD ) from day 1 to 12 of lactation; however, the difference was not significant (P > 0.05). At day 18 of lactation, Lf expression began to decline (Lf IOD /GAPDH IOD = 0.61), but the difference was not significant (P > 0.05). Based on these results, the variation in Lf expression levels during developmental stages may be related to its regulatory role in mouse mammary gland immunity.

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Bovine lactoferrin-derived peptides as novel broad-spectrum inhibitors of influenza virus

Cited by 55 publications

References 49 publications

Screening the anti infectivity potentials of native N- and C-lobes derived from the camel lactoferrin against hepatitis C virus

Screening the anti infectivity potentials of native N- and C-lobes derived from the camel lactoferrin against hepatitis C virus

Lactoferrin: A Powerful Antimicrobial Protein Present in Milk

Lactoferrin mRNA expression in mouse mammary glands during pregnancy and lactation

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