Computational analysis of mumps surface proteins reveals their interaction mechanism

No: 1521 Presentation at ESCV 2015: Poster 1 Computational analysis of mumps surface proteins reveals their interaction mechanism T. Vermeire1,∗, S. Vermaere2, S. Van Gucht3, V. Hutse3, L. Martens2, E. Vandermarliere2 1 WIV-ISP/VIB/UGent, Belgium 2 VIB/UGent, Belgium 3 WIV-ISP, Belgium Background: Mumps is a contagious childhood disease caused by the mumps virus (Paramyxoviridae). The virus is transferred via droplets and the disease is characterized by swelling of the parotid gland. Two major surface proteins, the haemaggluttininneuraminidase (HN) and the fusion (F) protein, play a key role in the infectious cycle of the virus. Even though little is known about the interaction between the two proteins, several studies suggest that a physical interaction between both proteins is necessary for fusion promotion. Recently, Welch et al. [1] identified an electronegative ring in the stalk domain of HN in Parainfluenza virus 5 (PIV5) (Paramyxoviridae), which interacts with a positively charged region on the F protein. Additionally, Bose et al. [2] found that domain II of the F protein might be involved in HN-F interaction.We have investigatedwhether this electronegative ring in HN is also present in the mumps virus HN protein, and if the positive region can be found on the F protein of mumps virus and coincides with domain II of the PIV5 F protein. Methods: We have built homology models of the HN and F protein of the mumps virus with the aid of FoldX. The templates usedwere 4JF7 and 4GIP, respectively. We have subsequently used PDB2PQR and the APBS tools in Pymol to visualize the electrostatic surface of both proteins. Results: For both the HN and F protein, we have used homology models tovisualize theelectrostatic solvent accessible surfaces. The visualization indicates that the region that correlates to the electronegative ring in PIV5 HN is also present in the mumps virus HN protein. Furthermore, in a comparative analysis of this region across 35members of the Paramyxoviridae,we found that the electronegative band is present in this region and is highly conserved. Moreover, through visualization of the electrostatic surface of the F protein, we found an electropositive region in the area that coincides with domain II of the F protein. Conclusion: Within this research, we have identified an electronegative and an electropositive region in the mumps virus HN and F proteins respectively, as seen previously for PIV5. Moreover, these regions seem to be conserved across the members of the Paramyxoviridae which indicates that the proposed mechanism of viral entry of PIV5 applies to all members of the Paramyxoviridae.