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Infection Biology Unit

Infection Biology Unit

Influenza viruses pose a global health threat, particularly to infants and the elderly. The viruses constantly change. As a consequence, vaccines have to be constantly adapted and therapeutics may cease to be effective. Therefore, we seek to develop novel influenza therapies. One focus of our work is on the host cell protease TMPRSS2 since we obtained evidence that TMPRSS2 depend on the protease for acquisition of infectivity and spread in the host. Moreover, we are investigating how defective interfering particles (DIPs) can be generated in the absence of infectious virus and how DIPs inhibit influenza virus infection.

Emerging viruses that are transmitted from animals to humans may cause severe disease. Outbreaks frequently occur abroad but the responsible viruses might be imported into Germany due to infected travelers. We are investigating how emerging viruses interact with host cells and cause disease. A recently started project focuses on lymphocytic choriomeningitis virus (LCMV). LCMV is related to the highly pathogenic Lassa virus, circulates globally and is responsible for outbreaks of lethal hepatitis in marmoset colonies. Moreover, LCMV may cause severe disease in immunosuppressed patients and can constitute a threat to pregnant woman and their unborn children. In addition to LCMV and Ebola virus we are also investigating MERS coronavirus. The aim of our research is to develop cell culture systems that allow predicting transmissibility and thus pandemic potential of novel MERS coronavirus variants.

Another focus of our research is on primate herpesviruses. The transmission of herpes B virus from macaques to humans as well as transmission of related viruses among non-human primates can cause serve disease. We are investigating which viral and host factors determine whether infection will result in severe disease. Moreover, we are developing diagnostics for herpesvirus infections of non-human primates. Finally, we are offering diagnostics for many other viral infections of non-human primates, including a chip-based antibody detection system useful for screening of non-human primate colonies.

Recent publications summarized in three sentences

14.08.2019

Novel technique to analyze interactions between IFITM proteins

Interferon-induced transmembrane proteins (IFITM) are cellular proteins that can block infection by diverse viruses. It has been suggested that IFITM-IFITM interactions are required for antiviral activity but quantifying these interactions is technically challenging. This manuscript reports a fluorescence resonance energy transfer (FRET)-based system that allows quantification of IFITM-IFITM interactions in cells via fluorescence-activated cell scanning (FACS).

Winkler et al, Analysis of IFITM-IFITM Interactions by a Flow Cytometry-Based FRET Assay. Int J Mol Sci., 2019, 8;20(16). pii: E3859.

30.07.2019

MERS-coronaviruses from African dromedary camels can efficiently enter human cells

The MERS-coronavirus is endemic in the Middle East and is transmitted from camels, the natural reservoir, to humans, who may develop severe disease. Camels in Africa are also infected by the virus but seem to harbor viral variants with reduced capacity to spread in human cells, which might account for the absence of documented MERS cases in Africa. The present study provides evidence that viruses from African camels might enter human cells with high efficiency, indicating that a step in viral replication other than entry is limiting viral spread in human cells.

Kleine-Weber et al, Spike proteins of novel MERS-coronavirus isolates from North- and West-African dromedary camels mediate robust viral entry into human target cells. Virology. 2019 Jul 19;535:261-265..

01.03.2019

A system for production of defective interfering particles

Defective interfering particles (DIP) inhibit influenza virus infection and are being developed for influenza therapy. However, so far, DIPs can only be produced joinlty with infectious virus, which is associated with safety concerns. Here, we report that a cell line stably expressing the viral protein PB2 is suitable for production of segment 1-based DIPs in the absence of infectious virus.

Bdeir et al. A system for production of defective interfering particles in the absence of infectious influenza A virus. PLoS One. 2019 Mar 1;14(3):e0212757.

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