Biomedical subjects

Lucilla Seganti

Publications and source records attributed to Lucilla Seganti.

9 recordsLinked to original sources

PubMed2006

Lactoferrin inhibits early steps of human BK polyomavirus infection.

Lactoferrin, a member of the transferrin family, is a bi-globular iron binding glycoprotein, found in milk, exocrine secretions of mammals, and in secondary granules of polymorphonuclear neutrophiles that plays an important role in the defence against various pathogenic microorganisms. Previous studies in different virus-cell systems showed that lactoferrin is a potent inhibitor of different enveloped and naked virus infection. In this research we studied the effect of lactoferrin on BK polyomavirus, a human naked double-stranded DNA virus responsible for productive, persistent, and latent infections of the urinary tract. Results obtained demonstrate that lactoferrin treatment prevents early steps of BK virus infection in Vero cells, at the level of the adsorption phase, probably through the interaction with capsidic structures, although a lactoferrin-BK virus competition for cell plasma-membrane receptors cannot be ruled out.

Animals↗

PubMed2004

Antiviral activity of lactoferrin towards naked viruses.

It is well known that lactoferrin (Lf) is a potent inhibitor towards several enveloped and naked viruses, such as rotavirus, enterovirus and adenovirus. Lf is resistant to tryptic digestion and breast-fed infants excrete high levels of faecal Lf, so that its effect on viruses replicating in the gastrointestinal tract is of great interest. In this report, we analysed the mechanism of the antiviral action of this protein in three viral models which, despite representing different genoma and replication strategies, share the ability to infect the gut. Concerning the mechanism of action against rotavirus, Lf from bovine milk (BLf) possesses a dual role, preventing virus attachment to intestinal cells by binding to viral particles, and inhibiting a post adsorption step. The BLf effect towards poliovirus is due to the interference with an early infection step but, when the BLf molecule is saturated with Zn+2 ions, it is also capable of inhibiting viral replication after the viral adsorption phase. The anti-adenovirus action of BLf takes place on virus attachment to cell membranes through competition for common glycosaminoglycan receptors and a specific interaction with viral structural polypeptides. Taken together, these findings provide further evidence that Lf is an excellent candidate in the search of natural agents against viral enteric diseases, as it mainly acts by hindering adsorption and internalisation into cells through specific binding to cell receptors and/or viral particles.

Adenoviridae↗

PubMed2004

Lactoferrin functions: current status and perspectives.

Lactoferrin, an iron-binding glycoprotein synthesized by neutrophils and exocrine glands, plays an important role in human innate defense mechanisms against bacteria, fungi, and viruses. First, a bacteriostatic activity of lactoferrin, depending on iron withholding to bacteria, and successively a bactericidal iron-independent effect, related to its binding on bacterial surfaces, was recognized. Many other functions have been ascribed to this cationic protein, including the inhibiting action toward bacterial adhesion and invasion of target host cells. Recent research also reported the lactoferrin influence on bacterial aggregation and biofilm development of Pseudomonas aeruginosa and Streptococcus mutans. The different lactoferrin functions can be justified by different physicochemical properties of the molecule, which include the iron-binding capability, the binding to anionic cell surfaces and molecules, and serine protease activity.

Anti-Bacterial Agents↗

PubMed2004

Lactoferricin influences early events of Listeria monocytogenes infection in THP-1 human macrophages.

Bovine lactoferrin (BLf) and its derivative peptide lactoferricin B (LfcinB) are known for their antimicrobial activity towards several pathogens, including Listeria monocytogenes, a food-borne Gram-positive invasive bacterium that infects a wide variety of host cells, including professional phagocytes. To add further information on the antibacterial effects of these compounds, the influence of BLf, LfcinB and the antimicrobial centre of LfcinB, the hexapeptide LfcinB(4-9), on the invasive behaviour of L. monocytogenes was analysed in IFN-gamma-activated human macrophagic cells (THP-1). Significant inhibition of bacterial entry in THP-1 cells was observed at LfcinB concentrations that were unable to produce any bacteriostatic or bactericidal effect, compared with BLf and LfcinB(4-9) peptide. This inhibition occurred when LfcinB was incubated during the bacterial infection step and was not due only to competition for common glycosaminoglycan receptors. Assays performed through a temperature shift from 4 to 37 degrees C showed that inhibition of invasion took place at an early post-adsorption step, although an effect on a different step of intracellular infection could not be ruled out.

Animals↗

PubMed2003

Heparin-interacting sites of bovine lactoferrin are involved in anti-adenovirus activity.

Lactoferrin, a member of the transferrin family of approximately 80 kDa, consists of a single polypeptide chain folded in two symmetric, globular lobes (N- and C-lobes), each able to bind one ferric ion. This glycoprotein, found in physiological fluids of mammals, plays an important role in immune regulation and in defense mechanisms against bacteria, fungi, parasites, and viruses. Although the antiviral activity of lactoferrin is one of the major biological functions of such protein, the mechanism of action is still under debate. We have investigated both the role of tryptic fragments of bovine lactoferrin and the mechanism of lactoferrin antiviral effect toward adenovirus infection in HEp-2 cells. The results obtained demonstrated that the anti-adenovirus activity of lactoferrin is mediated by the N-terminal half of the protein as the N-lobe was able to inhibit adenovirus infection, even if at lower extent than undigested lactoferrin, whereas C-lobe was ineffective. The results also showed that the anti-adenovirus action of lactoferrin and of its N-terminal peptide lactoferricin took place on virus attachment to cell membrane, mainly through competition for common glycosaminoglycan receptors. The data provide evidence that the anti-adenovirus activity of lactoferrin is mediated mainly by the cluster of positive charges at the N-terminus of whole molecule and that the N-terminal peptide lactoferricin alone is sufficient to prevent infection.

Adenoviruses, Human↗

PubMed2003

Bovine lactoferrin inhibits adenovirus infection by interacting with viral structural polypeptides.

We recently demonstrated that lactoferrin, an antimicrobial glycoprotein, can inhibit adenovirus infection by competing for common glycosaminoglycan receptors. This study further characterizes the antiadenovirus activity of the protein, thus demonstrating that lactoferrin neutralizes infection by binding to adenovirus particles and that its targets are viral III and IIIa structural polypeptides.

Adenoviridae↗

PubMed2002

Antiadenovirus activity of milk proteins: lactoferrin prevents viral infection.

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.

Adenovirus Infections, Human↗

PubMed2002

Effect of acid adaptation on the fate of Listeria monocytogenes in THP-1 human macrophages activated by gamma interferon.

In Listeria monocytogenes the acid tolerance response (ATR) takes place through a programmed molecular response which ensures cell survival under unfavorable conditions. Much evidence links ATR with virulence, but the molecular determinants involved in the reactivity to low pHs and the behavior of acid-exposed bacteria within host cells are still poorly understood. We have investigated the effect of acid adaptation on the fate of L. monocytogenes in human macrophages. Expression of genes encoding determinants for cell invasion and intracellular survival was tested for acid-exposed bacteria, and invasive behavior in the human myelomonocytic cell line THP-1 activated with gamma interferon was assessed. Functional approaches demonstrated that preexposure to an acidic pH enhances the survival of L. monocytogenes in activated human macrophages and that this effect is associated with an altered pattern of expression of genes involved in acid resistance and cell invasion. Significantly decreased transcription of the plcA gene, encoding a phospholipase C involved in vacuolar escape and cell-to-cell spread, was observed in acid-adapted bacteria. This effect was due to a reduction in the quantity of the bicistronic plcA-prfA transcript, concomitant with an increase in the level(s) of the monocistronic prfA mRNA(s). The transcriptional shift from distal to proximal prfA promoters resulted in equal levels of the prfA transcript (and, as a consequence, of the inlA, hly, and actA transcripts) under neutral and acidic conditions. In contrast, the sodC and gad genes, encoding a cytoplasmic superoxide dismutase and the glutamate-based acid resistance system, respectively, were positively regulated at a low pH. Morphological approaches confirmed the increased intracellular survival and growth of acid-adapted L. monocytogenes cells both in vacuoles and in the cytoplasm of interferon gamma-activated THP-1 macrophages. Our data indicate that preexposure to a low pH has a positive impact on subsequent challenge of L. monocytogenes with macrophagic cells.

Adaptation, Physiological↗

PubMed2002

Antiviral activity of ovotransferrin discloses an evolutionary strategy for the defensive activities of lactoferrin.

Ovotransferrin (formerly conalbumin) is an iron-binding protein present in birds. It belongs to the transferrin family and shows about 50% sequence homology with mammalian serum transferrin and lactoferrin. This protein has been demonstrated to be capable of delivering iron to cells and of inhibiting bacterial multiplication. However, no antiviral activity has been reported for ovotransferrin, although the antiviral activity of human and bovine lactoferrins against several viruses, including human herpes simplex viruses, has been well established. In this report, the antiviral activity of ovotransferrin towards chicken embryo fibroblast infection by Marek's disease virus (MDV), an avian herpesvirus, was clearly demonstrated. Ovotransferrin was more effective than human and bovine lactoferrins in inhibiting MDV infection and no correlation between antiviral efficacy and iron saturation was found. The observations reported here are of interest from an evolutionary point of view since it is likely that the defensive properties of transferrins appeared early in evolution. In birds, the defensive properties of ovotransferrin remained joined to iron transport functions; in mammals, iron transport functions became peculiar to serum transferrin, and the defensive properties towards infections were optimised in lactoferrin.

Animals↗