We are studying negative strand RNA viruses (Mononegavirales) including the neurotropic rabies virus (Rhabdoviridae) and the haematotropic measles virus (Paramyxoviridae) to learn how they exploit the cellular machineries and how they trick the host immune system. Recombinant viruses with defined gene defects or mutations are being used to reveal the contribution of individual virus proteins to virus replication host cell interplay, and viral spread. Our initial observation that the rabies virus G protein is dispensable for virus budding and can be replaced by other viral glycoproteins (pseudotyping) but is essential for the typical transsynaptic spread of the virus provided the basis for the establishment of the first viral mono-transsynaptic tracing system (Wickersham et al., Neuron, 2007). Pseudotyped delta G rabies viruses (ΔG RABV) have emerged as gold standard for mapping of direct synaptic connections and analysis of neuronal circuits in the central and peripheral nervous system, which is a fundamental pillar of modern neuroscience (Ghanem and Conzelmann, 2016). In combination with optogenetics and in vivo imaging methods such tracers are opening entirely new avenues of investigation in neuroscience and help in answering major outstanding questions of connectivity and function of the nervous system.
Ghanem A, Conzelmann KK (2016). G gene-deficient single-round rabies viruses for neuronal circuit analysis. Virus Res 216:41-54.
Wertz A, Trenholm S, Yonehara K, Hillier D, Raics Z, Leinweber M, Szalay G, Ghanem A, Keller G, Rózsa B, Conzelmann KK, Roska B (2015). Single-cell-initiated monosynaptic tracing reveals layer-specific cortical network modules. Science 349(6243):70-74
Foster E, Wildner H, Tudeau L, Haueter S, Ralvenius WT, Jegen M, Johannssen H, H&uoml;sli L, Haenraets K, Ghanem A, Conzelmann KK, Bösl M, Zeilhofer HU(2015). Targeted Ablation, Silencing, and Activation Establish Glycinergic Dorsal Horn Neurons as Key Components of a Spinal Gate for Pain and Itch. Neuron 85(6):1289-1304.
Bergami M, Masserdotti G, Temprana SG Motori E, Eriksson T, Göbel J, Yang SM, Conzelmann KK, Schinder AF, Götz M, Berninger B(2015). A critical period for experience-dependent remodelling of adult-born neuron connectivity. Neuron 85(4):710-717.