Abstract
Toscana virus is an emerging sandfly-borne bunyavirus in Mediterranean Europe responsible for neurological diseases in humans. It accounts for about 80% of paediatric meningitis cases during the summer. Despite the important impact of Toscana virus infection-associated disease on human health, currently approved vaccines or effective antiviral treatments are not available. In this research, we have analyzed the effect of bovine lactoferrin, a bi-globular iron-binding glycoprotein with potent antimicrobial and immunomodulatory activities, on Toscana virus infection in vitro. Our results showed that lactoferrin was capable of inhibiting Toscana virus replication in a dose-dependent manner. Results obtained when lactoferrin was added to the cells during different phases of viral infection showed that lactoferrin was able to prevent viral replication when added during the viral adsorption step or during the entire cycle of virus infection, demonstrating that its action takes place in an early phase of viral infection. In particular, our results demonstrated that the anti-Toscana virus action of lactoferrin took place on virus attachment to the cell membrane, mainly through a competition for common glycosaminoglycan receptors. These findings provide further insights on the antiviral activity of bovine lactoferrin.
Highlights
Toscana virus (TosV) is an enveloped, negative-strandedRNA virus, with a genome consisting of three segments: small (S), medium (M), and large (L), encoding the nucleoprotein (N) and a non-structural protein (NSs), the envelope glycoproteins (GN and GC), and a non-structural protein (NSm), and the large protein (L, the viral RNA-dependent RNA polymerase), respectively [1,2]
Twofold serial dilutions of protein from 2 mg/mL in Dulbecco’s modified Eagle’s medium (DMEM) were incubated with Vero cells for 48 and 72 h at 37 °C
BLf did not affect any of the cytotoxicity parameters up to the highest dose
Summary
RNA virus, with a genome consisting of three segments: small (S), medium (M), and large (L), encoding the nucleoprotein (N) and a non-structural protein (NSs), the envelope glycoproteins (GN and GC), and a non-structural protein (NSm), and the large protein (L, the viral RNA-dependent RNA polymerase), respectively [1,2]. It was first isolated in 1971 from sandfly, Phlebotomus perniciosus, collected in the Toscana region of Central Italy [3,4]. Infections without central nervous system involvement have been described [15]
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