Antiadenovirus activity of milk proteins: lactoferrin prevents viral infection. Antiviral Res. 53, 153-158

Institute of Microbiology, University La Sapienza, Rome, Italy.
Antiviral Research (Impact Factor: 3.94). 03/2002; 53(2):153-8. DOI: 10.1016/S0166-3542(01)00197-8
Source: PubMed


Different milk proteins were analysed for their inhibitory effect on adenovirus infection in vitro. Proteins investigated were mucin, alpha-lactalbumin, beta-lactoglobulin, bovine lactoferrin, and human lactoferrin. Results obtained demonstrated that mucin, alpha-lactalbumin, and beta-lactoglobulin did not prevent the viral cytopathic effect, whereas lactoferrin was able to inhibit adenovirus replication in a dose-dependent manner. Further experiments were carried out in which lactoferrin was added to the cells during different phases of viral infection. Results obtained showed that lactoferrin was able to prevent viral replication when added both before, or during the viral adsorption step, or when present during the entire replicative cycle of adenovirus, demonstrating that its action takes place on an early phase of viral replication.

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    • "Lf possesses antiviral activity against numerous viruses , which cause a set of very dangerous diseases in humans [113]. Among established Lf targets are human herpes simplex virus (HSV) types 1 and 2 [116] [170] [171] [172] [173] [174], adenovirus [175], human immunodeficiency virus (HIV) [115] [176] [177], human hepatitis C virus (HCV) [104] [178], human hepatitis B virus (HBV) [179] [180] [181], human cytomegalovirus (HCMV) [115] [116] [177] [182], poliovirus [183] [184], hantavirus [185-187], enterovirus 71 (EV71) [188], polycythemiainducing strain of Friend virus complex [189, 190], respiratory syncytial virus (RSV) [191, 192], human parainfluenza virus type 2 [193], alphavirus [194], human papillomavirus (HPV) [195, 196], polyomavirus BK (BK) [197, 198], rotavirus [199, 200], feline calicivirus [184], and others. "
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    ABSTRACT: Lactoferrin or lactotransferrin is a multifunctional glycoprotein found in blood circulation, mucosal surfaces, neutrophils, and in various secretory fluids, such as milk, bile, tears, nasal secretion, pancreatic juice, and saliva. The lactoferrin content in milk varies between different mammalian species and, within one species, between lactation periods. Although lactoferrin is known to be involved with immunoprotection, its functions are not limited to the regulation of innate immunity, but extend to iron transfer to cells, control of the level of free iron in blood and external secretions, interaction with DNA, RNA, heparin, and polysaccharides, and pronounced antimicrobial and antiviral activities. This multifunctionality is determined by the fact that lactoferrin belongs to the class of hybrid proteins possessing both ordered domains and functionally important intrinsically disordered regions. Structurally, lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa consisting of two homologous domains known as N-terminal and C-terminal lobes. These lobes are unevenly glycosylated (with the C-lobe typically containing more N-linked glycosylation sites). Each lobe can bind a single ferric ion concomitantly with one bicarbonate anion. Lactoferrin and its lobes have a wide spectrum of antimicrobial and antiviral activities, with the antimicrobial and antiviral potentials dependent on the type of microbes and viruses. Often, the N-lobe possesses the majority of antimicrobial activities. In addition, lactoferrin and its lobes possess clear anti-cancer, wound healing, anti-inflammatory, and immunomodulation activities.
    Current Protein and Peptide Science 09/2014; 15(8). DOI:10.2174/1389203715666140919124530 · 3.15 Impact Factor
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    • "Rotavirus Apo-bLF 50 mg/ml HT-29 Inhibition of cytopathic effect [26] Desialylated bLF 12 mg/ml Feline calicivirus (FCV, norovirus surrogate) bLF 1000 mg/ml Crandell-Reese feline kidney (CRFK) Inhibition of cytopathic effect [27] LFcin B 50e200 mg/ml Murine norovirus (MNV) bLF 5e15 mg/well Murine macrophage (Raw264.7) Inhibition of cytotoxic damage [28] Summer cold Adenovirus bLF 80 mg/ml HEp-2 Inhibition of cytopathic effect [35] hLF 560 mg/ml Adenovirus bLF 0.78 mM HEp-2 Inhibition of cytopathic effect [36] hLF 6.25 mM LFcin B 6.25 mM Adenovirus bLF Interaction with viral III and IIIa structural proteins [37] "
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    ABSTRACT: Although lactoferrin has many biological functions, the host-protective effects against pathogenic microorganisms including bacteria, fungi, and viruses are regarded as one of the most important. Here, we review research on the protective role of lactoferrin administration against common viral infections. Many studies have shown the in vitro antiviral activity of lactoferrin against viral pathogens that cause common infections such as the common cold, influenza, gastroenteritis, summer cold, and herpes, where lactoferrin inhibits mainly viral attachment to the target cells. Recently, studies indicating the in vivo protective effects of lactoferrin by oral administration against common viral infections have been increasing. For instance, norovirus is an extremely important emerging human pathogen that causes a majority of gastroenteritis outbreaks worldwide that may be a target candidate for lactoferrin. Lactoferrin consumption reduced the incidence of noroviral gastroenteritis in children and a similar effect was observed in a wide range of ages in a preliminary survey. A recent in vitro study reported that lactoferrin inhibits both cellular attachment of the murine norovirus, a virus closely-related to the human norovirus, and viral replication in the cells by inducing antiviral cytokines interferon (IFN)-α/β. Lactoferrin administration also enhances NK cell activity and Th1 cytokine responses, which lead to protection against viral infections. In conclusion, lactoferrin consumption may protect the host from viral infections through inhibiting the attachment of a virus to the cells, replication of the virus in the cells, and enhancement of systemic immune functions.
    Journal of Infection and Chemotherapy 08/2014; 20(11). DOI:10.1016/j.jiac.2014.08.003 · 1.49 Impact Factor
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    • "Human lactoferrin (apo-or Fe 3+ ), α-lactalbumin, β-lactoglobulin, human lactadherin, mucin, and immunoglobulin from milk could prevent rotavirus infection through the binding to structural viral protein VP4 [30] [37] [38] [40] [107] [108]. Also, the antiviral activity of lactoferrin against adenovirus has been attributed to the interaction of the milk protein with viral capsid proteins [60] [61] [69]. "

    Milk Proteins, 1 edited by Walter L. Hurley, 01/2012: chapter 2: pages 45-82; InTech., ISBN: 978-953-51-0743-9
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