Adaptation of influenza virus to blocking and removing of sialic acids from epithelial cells

Influenza virus can escape the host immune response owing to high mutations rate and antigenic flexibility. The influenza virus is an enveloped virus that expresses two surface glycoproteins, the haemagglutinin (HA) and the neuraminidase (NA), which play a key role in the process of infection. The HA protein binds sialic acids, mediates the binding to host cells and initiates the infection. The NA cleaves sialic acids and mediates the budding of new progeny viruses from the infected cells. Fc-fusion proteins have unique structure–function properties and play role in therapeutic application. In this research, we aim to develop an engineering Fc fusion protein which will be used for treatment of influenza virus infection. For this, the soluble recombinant glycoproteins of interest which are haemagglutinin and neuraminidase will be converted to a fusion molecule, using gamma immunoglobulin (IgG) isotype as the basis for generating Fc-fusion proteins. The influenza virus haemagglutinin was genetically linked to the N-terminus of human Fc, the influenza virus neuraminidase was genetically linked to the C-terminus of murine Fc and subsequently expressed in large quantity using a mammalian cell expression system. We are currently testing the ability of the HA-Ig and the NA-Ig to prevent the entry of the virus to the cells. In addition, we will test the adaptation of the virus following the fusion proteins’ treatment by analyzing viral mutations. Altogether, this project will provide new insights on the ability of influenza virus to escape treatments that either block sialic acids or remove sialic acids.