In situ correlative cryo-electron tomography and spatial lipid mapping of Influenza A virus-infected cells

• Applicant: Dr. Petr Chlanda
• Subject Area: Structural Biology ; Virology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437060729

Influenza A virus (IAV) is an important human pathogen causing annual epidemics and occasional pandemics. Therefore, in addition to considerable effort to develop a universal vaccine that would elicit an immune response against conserved epitopes, novel inhibitors of IAV replication cycle are needed. IAV and other enveloped viruses interact with host membranes and lipids on multiple levels during the replication cycle and thus the lipid homeostasis is often altered to the benefit of the viral replication. Neither how viruses control the membranes lipid composition nor what is the functional role of cholesterol distribution in membrane architecture and in the viral replication cycle is yet fully understood. Here we propose to use cryo-electron tomography to study the membrane remodeling in IAV infection during the assembly and budding. This will be combined with a novel technology called cryo-secondary ion mass spectrometry to image cholesterol distribution at sub-20 nm resolution in influenza A virus-infected cells. This approach will allow the mapping of cholesterol distribution in the 3D context of cellular membranes in native conditions for the first time. In this project, we will shed light on the importance of cholesterol distribution and cholesterol nanodomains in cellular membranes modified by IAV infection.

• DFG Programme: Research Grants
• International Connection: Luxembourg
• Partner Organisation: Fonds National de la Recherche
• Cooperation Partner: Dr. Tom Wirtz