My current research project aims at understanding lipid binding properties of the Marburg virus matrix protein-VP40 (MARV VP40). Marburg Virus is categorized as a class A pathogen by NIH. The matrix protein of Marburg virus is located underneath the lipid envelope of the virus and inside infected host cell, this protein interacts with host cell plasma membrane and facilitate the subsequent budding of the newly formed viral particles from the membrane. When I first started to work on this research project there was little known about lipid-protein interaction between VP40 protein and cell membranes. With my research I was able to obtain a comprehensive understanding of how Marburg VP40 protein mediate its host cell membrane interactions and the study was published in the Journal of Virology in 2015. With this study I was able to fill in some of the gaps in our understanding of this viral matrix protein. I’m currently focused further investigating how this membrane binding protein is able to change membrane structure of the plasma membrane to cause the budding of nascent viral particles. I plan to pursue an academic career where I will be able to conduct research and also participate in undergraduate teaching.
Marburg Virus matrix protein-VP40 is a non-specific anionic charge sensor
Marburg virus (MARV) is a lipid-enveloped filamentous virus from the Filoviridae family. Similar to its close relative Ebola virus (EBOV), MARV can cause often fatal hemorrhagic fever in humans and non-human primates. MARV harbors a negative-sense RNA genome, which encodes seven 7 genes. The matrix protein-VP40 of the MARV is the most abundantly expressed protein in the viral proteome. This protein is located underneath the lipid envelope of the virus providing structural stability to the viral particle and in an infected host cell MARV VP40 associate with the inner leaflet of the plasma membrane, facilitating budding of nascent viral particles. Until very recently crystal structure of MARV VP40 was not available and its cell membrane binding properties were poorly understood. We have used in vitro lipid binding assays and cellular analysis to investigate how MARV VP40 protein interacts with lipid membranes. Our studies show that MARV VP40 associate with cell membranes using non-specific electrostatic interactions in a highly charge dependent manner functioning as an anionic charge sensor. These electrostatic interactions occur between anionic phospholipids that are abundant in the inner leaflet of the plasma membrane and side chains of basic amino acid residues. Our studies are consistent with the recent crystal structure solved for MARV VP40 which shows that the protein is a dimer and has flat and extensive cationic lipid binding interface which is ideal to mediate non-specific electrostatic interactions.