Structural-Evolutionary Investigation of Phenuiviridae Membrane Fusion Proteins

Arboviruses are evolving pathogens causing various illnesses in animals and plants which can lead to health crisis and significant economic burden. Unlike many insect-borne animal pathogens, there are many arboviruses that are restricted to their insect host. The viral envelope glycoproteins have a key role in recognizing the host-cell attaching and internalizing the virus particle into the host-cell, followed by a carefully orchestrated step of membrane fusion that releases the viral genome into the host cytoplasm. The structural basis of the evolutionary processes of virus host selection and restriction are poorly understood. Here we investigate the emerging insect-restricted virus Badu phasivirus (BADUV) belongs to the family of Phenuiviride order: Bunyavirales. BADUV is a ssRNA(-) virus, with a tripartite genome. The two enveloped glycoprotein G_N and G_C play an important role in the process of the virus’ cell entry. Using structural and functional approaches we will depict a detailed mechanistic narrative for the entry of BADUV and for the roles that G_N and G_C play in it. We characterized and measure the activity of these glycoproteins ability to perform cell membrane fusion process in different cell lines. In parallel, we were able to obtain crystals from purified sG_N(262-520) and in the foreseeable future, we will determine G_N’s structure unraveling the new aspects on the mechanism of virus host-range selection. Deciphering the structural basis of the mechanistic differences between human-infecting viruses and insect-restricted viruses will unravel novel evolutionary paths of virus host-range selection.