apl. Prof. Dr. Barbara Müller
barbara.mueller
(at)med.uni-heidelberg.de
Phone: +49 6221 56–1325
Fax: +49 6221 56–5003
Dynamic Events in HIV‑1 Replication
Projects
We are interested in the biology of retroviruses, in particular the human immunodeficiency virus (HIV 1). With our work, we want to contribute to a detailed understanding of the intricate interactions of this important pathogen with its host cell during the viral replication cycle.
The interaction of a virus with its host cell is a highly dynamic process, involving ordered and regulated formation, transport, transformation and dissociation of (nucleo)protein complexes. Biochemical, electron microscopic and structural studies provide detailed images of HI virions and information about the composition of functionally important subviral complexes. However, these methods yield snapshots or ensemble data, which do not reflect the dynamics of individual events occurring in the infected cell. In contrast, modern fluorescence imaging techniques enable us to directly observe transport processes and protein interactions within living cells. Furthermore, super-resolution and correlative microscopy now bridge the gap between electron and light microscopy, allowing the visualization of subviral details via fluorescence microscopy. All these advanced imaging methods require attachment of fluorescent labels to the viral protein of interest.
Our aim is to analyze dynamic processes in HIV 1 replication in a quantitative manner. For this, we develop fluorescently labeled HIV 1 derivatives and fluorescent probes, which allow us to follow individual events in virus-cell interaction with high time resolution. These studies are combined with biochemical and virological analyses. In our current work, we particularly focus on the processes involved in the formation of the infectious HIV 1 capsid by assembly and proteolytic maturation, and on the fate and role of this capsid structure upon entry of the virus into a new host cell.
Responding to the COVID-19 pandemic, we are also involved in the development of novel assay systems and in several clinical studies. Although our main research field remains retrovirology, work on COVID-19 is currently continued.
Our main research interests are:
- HIV‑1 assembly and maturation
- Dynamics of post-entry events in retroviral replication