Cell Biology of Virus Infection
As obligate intracellular parasites viruses intimately rely on host cell factors for all stages of their replication. Our group is interested in deciphering the complex interactions that occur between poxviruses and their host cells during all stages of the infection cycle. We investigate how viruses initiate their internalization by endocytosis, and how they utilize transport within cellular endocytic systems to their advantage. We are also analyzing how the viral genome and accessory proteins escape into the cytosol, and how replication proceeds.
For these we combine cellular, molecular, and virological techniques with state-of-the-art technologies such as automated small compound and image-based siRNA screening, advanced proteomics, live cell microscopy, and electron microscopy. Our particular interests lie in uncovering novel mechanisms by which viruses subjugate host cell functions to facilitate their entry, replication, and spread.
Systematic analysis of the poxvirus lifecycle. Representative images of each of the stages of the virus lifecycle for which we have developed specific, quantitative, high- or medium- throughput assays.
Cell Reports on the cover: Vaccinia virus, the prototypic poxvirus, is complex in structure. Virions consist of a lipid bilayer surrounding a genome-containing core, which is flanked by two proteinaceous lateral bodies, the composition and function of which has remained enigmatic for over 40 years. The manuscript by Schmidt, Bleck et al. shows that poxvirus lateral bodies, akin to herpesvirus tegument, serve as delivery containers for viral immunomodulatory proteins. The cover image shows a collection of immunoelectron micrographs of vaccinia virions labeled for the viral protein F17, identified as a major lateral body component. Images by C.K.E. Bleck.
Traffic cover: The Great Escape Pictured are several vaccinia viruses (red) within LAMP1-positive (green) late macropinosomes. In the center a virus can been seen undergoing acid-mediate fusion from one of these late compartments. This image represents a still, from a live-cell imaging movie that accompanies the manuscript by Rizopoulos, Balistreri, et al. showing that vaccinia is a late penetrating virus that requires macropinosome maturation for productive infection. The original image has been rendered with saran wrap so that the macropinosomes appear to be floating in the cytoplasmic milieu.