Probe microscopy-based functional tracking of respiratory viruses to identify virus tropism
We aim to characterise virus tropism by identifying permissivecelltypesthatsupportcompletevirusrepli cation by using Tip-enhanced Raman Spectroscopy (TERS). TERS integrates atomic force microscopy (AFM) and near-field optical recordings with Raman spectroscopy, enabling direct, label-free characterisa tion of molecular organisation and thus visualisation of virus entry and exit at nanometer resolution.
Virus tropism is defined as the selective ability of a virus to infect specific host species, tissues, or cell types. It is determined by virus factors such as receptor binding and replication requirements, as well as by host determinants, including receptor availability and intracellular conditions.
Graphical overview of the three work packages: WP1: Experimental setup and model development. WP2: Nanoscale time-lapse study of virus and membrane samples, analysis of virus entry and exit. WP3: Correlative TERS, nanoIR, and AFM topography analysis of virus infection under the influence of ageing.
As a result, tropism ultimately defines whether productive replication occurs and thereby shapes virus pathogenesis, disease progression, and transmission. However, inferring tropism from virus properties alone remains difficult and typically requires elaborate infection experiments.
In this project, TERS will be employed to resolve virus entry and exit strategies with unprecedented spatial detail, Fig. C02.1. Beyondimaging, TERSprovidesmolecularfingerprintsandresolvesnanoscalesurfacestructures, thereby revealing chemical and conformational changes that accompany virus-cell interactions. Time-resolved nanoscale studies will further allow us to monitor replication at the level of single infection events and to detect heterogeneous infection patterns that are masked in bulk analyses. By combining structural and temporal information, we aim to precisely definethehostcellfactorsandphysiologicalstatesthatpermitorrestrictvirus replication, thus contributing directly to research goals G3 and G4. Our approach represents a novel, rapid, label-free, and phenotypic method to define virus tropism. In addition to TERS, we will employ nanoscale infrared spectroscopy (nanoIR), a technique that combines AFM with IR absorption to provide chemical composition and conformational information at nanometer resolution. The combination of nanoIR and TERS will yield complementary spectroscopic data to unravel structural changes during virus-cell interactions, potentially down to amino acid resolution. To further dissect the influence of host determinants on virus tropism, we will additionally apply a cellular senescence model.
This approach extends our nanoscale analyses by addressing how age-related cellular changes shape virus entry, replication, and release. Preliminary data indicate that virus load in senescent cells differs markedly from controls, thereby linking methodological innovation with a key biological question, as elderly populations are especially vulnerable in pandemics. Together, these technologies will enable dynamic, high-resolution visualisation of virus entry and budding, offering an innovative framework to redefine the study of virus tropism.
- WP 1: Experimental setup and model development (Deckert/Deinhardt-Emmer)
- WP 2: Nanoscale time-lapse study of virus and membrane samples (Deckert/Deinhardt-Emmer)
- WP 3: Correlative TERS, nanoIR, and topography analysis of virus infection (Deckert/Deinhardt-Emmer)
Team Members
N. N.
Doctoral Researcher
N. N.
Doctoral Researcher
Project-Specific Publications
2025
High-fat diet impairs microbial metabolite production and aggravates influenza A infection Journal Article
In: Cell Communication and Signaling, vol. 23, no. 1, pp. 359, 2025.
Sepsis in patients who are immunocompromised: diagnostic challenges and future therapies Journal Article
In: The Lancet Respiratory Medicine, vol. 13, no. 7, pp. 623–637, 2025.
Unraveling the Hierarchical Self-Assembly of Amphiphilic Block Copolymer-Peptide Conjugates by Tip-Enhanced Raman Spectroscopy Journal Article
In: Small, pp. 2502157, 2025.
2024
Tip-enhanced Raman scattering Journal Article
In: Nature Reviews Methods Primers, vol. 4, no. 1, pp. 47, 2024.
2023
Influenza virus-induced paracrine cellular senescence of the lung contributes to enhanced viral load Journal Article
In: Aging and disease, vol. 14, no. 4, pp. 1331, 2023.
Identification of RNA-containing virus particles using a triple correlative morphological and microscopic approach Journal Article
In: 2023.
Inside block copolymer micelles—tracing interfacial influences on crosslinking efficiency in nanoscale confined spaces Journal Article
In: Small, vol. 19, no. 20, pp. 2206451, 2023.
2021
Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and the correlation with tissue damage Journal Article
In: Elife, vol. 10, pp. e60361, 2021.
2020
Laser spectroscopic technique for direct identification of a single virus I: FASTER CARS Journal Article
In: Proceedings of the National Academy of Sciences, vol. 117, no. 45, pp. 27820–27824, 2020.
2015
A manual and an automatic TERS based virus discrimination Journal Article
In: Nanoscale, vol. 7, no. 10, pp. 4545–4552, 2015.