Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection

Abstract

Surfactant protein A (SP-A) and lactoferrin (LF) play important roles in innate immune systems in the respiratory mucous membranes. We investigated how SP-A and LF act against respiratory syncytial virus (RSV) infection. The present study indicated that RSV-induced IL-8 secretion from HEp-2 cells was up-regulated by SP-A (170% of control) but downregulated by LF (23% of control). RSV infectivity determined by viral titers and the uptake of FITC-labeled RSV were also increased by SP-A, but decreased by LF. To clarify the mechanism of these opposite effects, we examined the interactions of SP-A and LF with RSV F protein, the most important surface glycoprotein for viral penetration. RSV F protein was found to be the ligand for both SP-A and LF, but the manners of binding were different. LF directly interacted with the F 1 subunit, which involved antigenic sites of F protein. Contrarily, SP-A associated with the F 2 subunit, which was highly glycosylated. SP-A but not LF failed to interact with deglycosylated F protein. Moreover, SP-A initiated the hemolyzing fusion activity of F protein. These results suggest that SP-A and LF modulate RSV infection by different binding specificity to F protein.

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

“…11,12 Lf, an 80-kDa multifunctional cationic glycoprotein belonging to the transferrin family, possesses a variety of biological functions such as: influence on iron homeostasis, immunomodulation, and inhibitory activity towards different pathogens, including influenza viruses. 12,13 Bovine lactoferrin (bLf) is a potent inhibitor of different enveloped viruses [14][15][16][17][18][19][20][21][22][23] and, like lactoferrin of other mammalian species, is folded in two symmetric globular lobes, each one including two domains (N-lobe: N1 and N2; Clobe: C1 and C2). 24,25 It has been shown that the principal mechanism of bLf antiviral activity follows a direct binding to viral particles 20,[26][27][28] or to host cell receptor molecules.…”

Milk Derived Peptides with Immune Stimulating Antiviral Properties

“…Binding to cellular molecules interfering with viral attachment/entry [47,59] Hepatitis G virus lactoferrin Unknown [63] Respiratory syncytial virus lactoferrin, lactoperoxidase Binding to F1 subunit of RSV F protein to inhibit viral absorption [35,[44][45][46] Human immunodeficiency virus human and bovine lactoferrin, lactoperoxidase…”

“…Lactoferrin has also been demonstrated to inhibit the absorption and growth of respiratory syncytial virus in cell culture through direct interaction with the F(1) subunit of the viral F protein, which is the most important surface glycoprotein participating in viral penetration [44,45]. Blocking of viral entry like this, leads to downregulation of respiratory syncytial virus induced interleulin-8 secretion from the HEp-2 cells, which consequently leads to a dampening of the immune response as the low levels of interleukine-8 is inadequate to recruit neutrophils to phagocytose the viral antigen [46].…”

Collectins and Cationic Antimicrobial Peptides of the Respiratory Epithelia

“…This role can be explored by using SP-A 2/2 and SP-D 2/2 mice. The phenotypic features of SP-D 2/2 mice include Inhibits influenza virus hemagglutination and infectivity; binds high-mannose oligosaccharides present on HA of IAV 60,61 Binds to G and F proteins of RSV 82 Binds to F proteins of respiratory syncytial virus (RSV) 45,128 Hemagglutination inhibition and neutralization of bovine rotavirus 116 Fungi Binds glycoprotein gpA of cyst and trophozoite forms of Pneumocystic carinii, which enhances binding of organism to alveolar macrophages 27,68 Binds glycoprotein gpA of cyst and trophozoite forms of Pneumocystic carinii, which enhances binding of organism to alveolar macrophages 27,68 Binds to uncapsulated forms of Cryptococcus neoformans Binds to conidia and specific cell wall glycoproteins of Aspergillus fumigatus…”