How do viruses assemble at the single-particle level?

What is this research project about?

Single-particle Tracking of HCMV envelopment.

What is this research project about?

Human Cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus of high clinical importance that establishes lifelong latent infection in humans. It is the leading cause of congenital disabilities in the developed world and a significant cause of disease in immunocompromised patients, such as transplant, AIDS, or cancer patients. It has been ranked high priority for vaccine development for over 20 years. Still, despite continuing efforts, no licensed vaccine exists so far, and antiviral therapy currently is the only treatment option, with the development of viral resistance being a significant concern.

What’s the current status?

HCMV assembles in a complex order of consecutive morphogenesis events that are poorly understood at the spatiotemporal level. Highly resolved data is needed to determine how viruses assemble at the single-particle level and identify potential bottlenecks in these processes as specific pharmacological target structures.

Light and electron microscopy of an HCMV infected cell with multiviral bodies.
©Flomm et al. In BioRxiv

What are the project goals?

Our research aims to illuminate the spatiotemporal regulation of HCMV morphogenesis at the single-particle level. We use correlative three-dimensional live-cell microscopy electron microscopy to quantify the kinetics and dynamics of viral macromolecular complexes in living cells at the single-particle level and create computational pipelines to analyze large image datasets. Using these tools, we aim to define novel targets for inhibiting HCMV.

How do we get there?

Together with our colleagues at the MHH as well as at the CSSB in Hamburg, we combine molecular virology with cutting-edge light- and electron microscopy tools as well as structural biology and the computational infrastructure available at the Center for Structural Systems Biology (CSSB) in Hamburg to analyze how viruses assemble at the single-particle level.

3D-rendering of HCMV multiviral body contents.
©Flomm et al. In BioRxiv

Projectleaders

Project title: Spatiotemporal orchestration of HCMV morphogenesis

Prof. Dr. Jens Bosse

Projects: D1, D2, D3

CV & VIDEO

Project D3 Publications

Publications 2022

Intermittent bulk release of human cytomegalovirus. Flomm FJ, Soh TK, Schneider C, Wedemann L, Britt HM, Thalassinos K, Pfitzner S, Reimer R, Grünewald K, Bosse JB. PLoS Pathog. 2022 Aug 4

The unconventional way out – Egress of HCMV through multiviral bodies. Wedemann L, Flomm FJ, Bosse JB. Mol Microbiol.

Herpesvirus Replication Compartments: Dynamic Biomolecular Condensates? Enrico Caragliano, Wolfram Brune, Jens B. Bosse, Viruses

Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication. Caragliano E, Bonazza S, Frascaroli G, Tang J, Soh TK,Grünewald K, Bosse JB*, Brune W* (*co-corresponding authors, equal contribution) Cell Reports

A Unique Role of the Human Cytomegalovirus Small Capsid Protein in Capsid Assembly. Borst EM, Harmening S, Sanders S, Caragliano E, Wagner K, Lenac Roviš T, Jonjić S, Bosse JB, Messerle M.  mBio. 2022 Oct 26;13(5):e0100722. doi: 10.1128/mbio.01007-22. Epub 2022 Sep 6.

Publications 2021

Infection-induced chromatin modifications facilitate translocation of herpes simplex virus capsids to the inner nuclear membrane, V Aho, S Salminen, S Mattola, A Gupta, F Flomm, B Sodeik, JB Bosse, Maija Vihinen-Ranta, PLoS pathogens 17 (12), e1010132

KIR3DS1 directs NK cell-mediated protection against human adenovirus infections. Jung J, Ching W, Baumdick M, Hoffmann-Sieber H, Bosse JB, Koyro TF, Moeller K, Wegner L, Niehrs A, Russu K, Ohms M, Zhang W, Ehrhardt A, Duisters K, Spierings E, Hoelzemer A, Koerner C, Jansen S, Peine S, Koenigs I, Luetgehetmann M, Perez D, Reinshagen K, Lindemanns AA, Altfeld M, Berlderbos ME, Dobner T, Bunders M, (2021), Science Immunology, https://doi.org/10.1126/sciimmunol.abe2942

Concatemeric Broccoli reduces mRNA stability and induces aggregates. Rink MR, Baptista MAP, Flomm FJ, Hennig T, Whisnant AW, Wolf N, Seibel J, Dölken L, Bosse JB, (2021), PLOS One, doi: 10.1371/journal.pone.0244166 Article PLOS ONE 3,2

Identification of African Elephant Polyomavirus in wild elephants and the creation of a vector expressing its viral tumor antigens to transform elephant primary cells. Pearson VR, Bosse JB, Koyuncu OO, Scherer J, Toruno C, Robinson R, et al. (2021)  PLoS ONE 16(2): e0244334.

Human Adenovirus Type 5 Infection Leads to Nuclear Envelope Destabilization and Membrane Permeability Independently of Adenovirus Death Protein. Pfitzner S, Bosse JB, Hofmann-Sieber H, Flomm F, Reimer R, Dobner T, Grünewald K, Franken LE, International Journal of Molecular Sciences (IJMS) 2021).

Egress of human cytomegalovirus through multivesicular bodies. Flomm F, Soh TK, Britt H, Schneider C, Reimer R, Thalassinos K, Grünewald K, Bosse JB. bioRxiv 2020

Publications 2020

Fluorescent Protein Tagging of Adenoviral Proeins PV and PIX Reveals ‘Late Virion Accumulation Compartment’. Sieber H, Bosse JB, Franken LE, Grünewald K, Dobner T, (2020), PLOS Pathogens

Publications of the Project D3