Virus Structure & Assembly
2/5/2013 1:45:00 PM
ELUCIDATING THE MECHANISM OF EBOLA VIRUS ASSEMBLY AND BUDDING
, Smita P. Soni
, Robert V. Stahelin
Dep't of Chemistry and Biochemistry,University of Notre Dame, Notre Dame, IN, USA,
Eck Institute for Global Health, Notre Dame, IN, USA,
Dep't of Biochemistry and Molecular Biology, IUSM-SB, South Bend, IN, USA.
Ebola virus from the filoviridae family is characterized by internal and external bleeding in primates due to coagulation abnormalities induced by the virus at the onset of the infection. With no vaccines or treatment, Ebola is classified as bio-safety level IV agent with the potential to be used as a biological weapon. Details of virus assembly are poorly understood. Evidence suggests that matrix protein VP40 is the main driving force for assembly and budding. Generation of new virus involves a cascade of cellular events that recruit the viral genome, the matrix proteins and subsequent acquisition of the viral envelope from the host cell. The new virus like particle (VLP) forms at a bud site at the inner leaflet of the plasma membrane and can serve as a primary therapeutic target for inhibiting Ebola virus replication. Preliminary results demonstrate that VP40 alone assembles in mammalian cells into VLPs independent of other viral proteins. It binds to the plasma membrane with nanomolar affinity and possesses the ability to modify membrane structure. VP40 induces membrane curvature changes, an important step for bud formation and egress of the newly formed virus. This project is aimed at elucidating the mechanistic details of VP40 assembly on the plasma membrane using an interdisciplinary approach. Specifically, we have employed in vitro lipid binding and curvature assays with cellular scanning and single molecule microscopy to investigate the basis of VP40 lipid binding, membrane bending and viral egress. Our results further demonstrate that VP40 oligomerizes on the plasma membrane in a PS-dependent manner and also remodels actin network for assembly and maturation. Our results represent a key step to understanding the general principles governing the remodeling of membrane by matrix proteins from lipid enveloped viruses such as Ebola and HIV.
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