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APPROACHING VIRUS LIFE CYCLE WITH ELECTRON MICROSCOPY
Dr. Li Xing
US Air Force Research Lab
Monday, April 24, 2017, Colloquia Auditorium
Electron microscopy has been one of the robust tools in characterizing the life cycle of viruses, such as Semliki Forest Virus (SFV), an alphavirus that belongs to Togavirus family and causes encephalitis in human. The viral particle of SFV is composed of a nucleocapsid enclosed by a lipid-anchored glycoprotein spikes and infects cell through clathrin-dependent endocytosis pathway where it releases the nucleocapsid into the cytoplasm after membrane fusion at the late endosome. Cryo-electron microscopy and single particle reconstruction revealed the structure of SFV virion that both the nucleocapsid and surface spikes adapted into icosahedral symmetry with T4 surface lattice and that the connection between nucleocapsid protein and C-terminal tail of the glycoprotein stabilizes the particle integrity. Mutation at nucleocapsid does not changed the assembly of the viral particle although truncation at the RNA-binding domain inhibits the formation of nucleocapsid in cytoplasm. SFV replication induces rearrangement on the membrane system and results in formation of large cytopathic vesicles in host cell. We studied the cytopathic vesicle in cyro-fixed cells with electron tomography and revealed the spindle shape of vesicles that contains viral glycoproteins. Therefore the cytopathic vesicle act as the vehicle for glycoprotein transportation from Golgi complex to plasma membrane for virus budding. Our work demonstrates the important role of electron microscopy in the capacity of function analysis by adding on the structure of macromolecular complexes and the morphology of the surrounding environments.
Biography of Li Xing
Li Xing received her PhD in Structural Biochemistry from Karolinska Institute, Sweden in 2002. From there, she worked as a Research Scientist in Karolinska Institute for three years, studying virus-cell interactions with cryo-electron microscopy and image processing. During that time, Li Xing was rewarded a research award from Swedish Research Council for the study of Hepatitis E virus-like particles. She then moved to University of California at Davis and continue studying on virus-cell interactions and also performed research on microscopic characterization of drug delivery in cancer cells. Li Xing moved to Air Force Research Laboratory in 2015 as a contractor performing the research of biosensor with focus on the characterization of peptide-peptide interactions on graphene-based FET sensor.
Date:
Monday, April 24, 2017 - 11:00