Novel Insights on the Recognition of Sialylated Glycans by Hn Protein of Mump Virus Revealed by NMR and Molecular Modeling

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Novel Insights on the Recognition of Sialylated Glycans by Hn Protein of Mump Virus Revealed by NMR and Molecular Modeling

Rosa Ester Forgione 1 , Antonio Molinaro 1 , Roberta Marchetti 1 , Alba Silipo 1

1 University of Naples ''Federico II'', Naples, Italy

Protein– glycans interactions set the basis of several molecular recognition processes and are implicated in events like cell–cell interactions, signal transduction, inflammation, viral entry and host bacteria recognition, thereby participating in disease, defense and symbiosis [1,2]. Of particular interest is the role of sialylated glycans in mediating bacterial and viral infections [3], acting as receptors for many pathogens, including paramyxoviruses as Mumps virus [4] (MuV).

MuV represents the main cause of mumps disease, a systemic viral illness characterized by painful swelling the salivary glands, typically the parotid glands [5]. The pathogenesis of the virus in humans is a long-standing question. Although several vaccines have been developed, unexpectedly, MuV still causes outbreaks, even in highly vaccinated populations worldwide [6].

Within this frame, the present work is focused on the study of the molecular recognition between the MuV attachment protein hemagglutinin-neuraminidase (MuV-HN) and sialylated ligands. The MuV-HN protein displays several functions essential for virus entry and infection, since is located on the surface of the MuV and mediates the viral attachment to the host cell surface. Actually, MuV-HN recognizes sialic acid-containing glycoconjugates on cell surfaces, thus assisting the fusion activity of the viral cell surface F protein, leading to the penetration of MuV into the host cell. In combination to that, the HN neuraminidase activity removes the sialic acid from progeny virus particles thereby avoiding viral self-agglutination [7].

Nuclear magnetic resonance (NMR) techniques combined with computational studies were applied to dissect the interaction between HN protein and sialylated ligands. Novel insights on the kinetic of the hydrolisis reaction at the basis of the neuraminidase activity of HN have been provided; moreover, the definition of the bioactive conformation and of the binding epitope of the sialylated ligands allowed a deeper comprehension of the biological processes at the basis of MuV- HN infectivity. Our results represent a first step toward the development of more effective antiviral vaccines to prevent MuV infection and reinfection globally.

Schnaar, R. L. J. Allergy Clin. Immunol. 2015, 135, 609–615.

Rabinovich, G. A. and Croci, D. O. Immunity 2012, 36, 322–335.

Stehle, T. and Khan, ZM. J. Virol. 2014; 88(14).

Kubota, M. et al. Proc. Natl. Acad. Sci. 2016, 113, 11579–11584.

Latner, D.R. and Hickmann, C.J. PLoS Pathog. 2015, 11(5).

Rubin, S.A. et al. J Virol. 2012, 86(1), 615–620.

Kelm, S. and Schauer, R. Int. Rev. Cytol. 1997, 175, 137–240.

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