Membrane virology of viral infection
We are interested in studying how viruses interact with cellular membranes and lipids during infection. We use cryo-electron microscopy techniques in conjunction with other imaging methods, such as fluorescence microscopy and imaging mass spectrometry, to structurally characterize influenza A and Ebola virus protein-membrane interactions during entry.
Influenza A virus (IAV) and Ebola virus (EBOV) are human pathogens responsible for acute respiratory inflammation and highly lethal hemorrhagic fever syndrome, respectively. The Ebola virus outbreaks of 2013 and 2018, as well as the annual epidemics and occasional pandemics due to influenza A virus underscore the need for unraveling mechanistic aspects of the virus replication cycle and the development of novel virus inhibitors. Both viruses form long filamentous membrane enveloped virions that must enter the host cell and undergo membrane fusion in order to establish a successful infection. The mechanism of IAV and Ebola virus disassembly and membrane fusion are not completely understood and have not been structurally analyzed inside the cells.
We apply cryo-electron microscopy techniques to provide structural details of IAV and Ebola virus disassembly and membrane fusion in vitroand in situ. We use a cryo-correlative light and electron microscopy workflow that allows us to study IAV and EBOV entry and membrane fusion at high resolution inside the cells under native conditions. Our lab studies (i) viral protein conformational changes occurring during entry; (ii) the role of cholesterol in viral membrane fusion and (iii), the function of host membrane fusion restriction factors, such as interferon inducible transmembrane proteins.
Influenza A virus (A), Ebola virus-like particles (B) and a cytoplasm area of a lung cell with organelles imaged by cryo-electron microscopy and tomography (C). (MVB = Multivesicular body).