BK virus (BKV) is a human naked polyomavirus respon-sible for productive, persistent, and latent infections of the urinary tract. The presence of its DNA has been revealed in various tumors. The severity of BKV infection in immuno-compromised hosts has improved the search for selective antiviral agents, but hitherto only few effective compounds have been identified. Lactoferrin (Lf), a member of the transferrin family, is a biglobular iron-binding glycoprotein found in milk, exocrine secretions of mammals, and in sec-ondary granules of polymorphonuclear neutrophiles. Lf was established as playing an important role in the defence against various pathogenic microorganisms. Previously, we demonstrated that Lf is a potent inhibitor of infection by some enveloped and naked viruses in different cell systems. In this research, we investigated the effect of this glycopro-tein on BKV infection. The experiments were carried out synchronizing infection by a temperature shift and viral rep-lication in Vero cells and was monitored measuring BKV DNA synthesis by semiquantitative PCR assay of the TAG region. The results showed that inhibition of BKV replica-tion already occurred when Lf was added during viral ad-sorption. Moreover, pre-incubation of Lf with BKV before infection inhibited viral replication by 98%, suggesting a specific binding of Lf to the virions. Finally, the direct inter-action of Lf to BKV particles was demonstrated by hemag-glutination inhibition assays and visualized by transmission electron microscopy. These results demonstrated that, simi-larly to data obtained with other viruses, Lf inhibits the early steps of infection through a direct interaction with vi-ral structures. Further studies will be carried out to better clarify the effects of Lf on human polyomavirus replication.
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