Effects of the Cellular SUMOylation System on the Influenza Nuclear Export Protein (NEP)

The high genetic compatibility between the 2009 H1N1 pandemic swine flu and the highly pathogenic H5N1 bird flu viruses indicates that the odds of a deadly bird flu strain mingling its genetic material with a human virus and becoming easily transmissible among humans are at an all-time high. This fact stresses the urgent need for new treatment and prevention methods to combat influenza. Our current anti-influenza weapons include vaccination and two type of antivirals that target specific viral components (the so-called M2 ion channel inhibitors and the neuraminidase inhibitors). However, the high genetic variability of the virus enables it to easily circumvent by favoring the development of mutations that either, change the antigenic makeup of the virus making it unrecognizable by the immune effectors stimulated by vaccination, or confer resistance against the antivirals indicated above. A promising new alternative for the development of broad-spectrum antivirals is to develop small molecules capable of either, decreasing the activity or abundance of cellular components essential for viral replication, or increasing the activity or abundance of cellular components endowed with antiviral activity. In this project we aim to further characterize the role played by the so-called cellular SUMOylation system during influenza virus infections, to determine whether it may provide new targets for the development of innovative anti-influenza therapies. Specifically, my work focuses on delineating the molecular effects mediated by the SUMOylation of the viral protein NEP, an essential viral factor required for the export of viral components from the cell nucleus