Karl-Klaus Conzelmann (1955-2025)
04.04.2025
Klaus on one of the legendary Gene Center retreat hikes
(2005, ©KPH)
It is with great sadness that we received the news of the passing of our colleague and good friend, Professor Karl-Klaus Conzelmann. Klaus was a long-standing member of the Gene Center Munich and a former faculty member at the Max von Pettenkofer Institute. He was one of the pillars who shaped the Gene Center’s international reputation in molecular virology.
Klaus was not only a visionary scientist but also a dedicated mentor and a sought-after collaborator. He embodied a rare combination of intellectual rigor and deep understanding of his field of expertise, coupled with cross-disciplinary curiosity. His pioneering contributions to reverse genetics using rabies virus cDNA transformed the molecular manipulation of non-segmented RNA viruses, laid the groundwork for an entire generation of viral vector technologies, enabled synaptic tracing in neurobiology, and culminated in a promising vaccine design developed by his lab during the SARS-CoV-2 pandemic.
Karl-Klaus Conzelmann began his research career in virology at the Federal Research Center for Virus Diseases of Animals in Tübingen (now the Friedrich-Loeffler-Institute), where he studied viruses of veterinary and public health relevance. In parallel, Klaus pioneered reverse genetics for negative-strand RNA viruses. In a landmark study in 1994 (EMBO J), his lab reported the first recovery of infectious rabies virus from a full-length cDNA clone—a technique that initiated a whole new field of research. Today, every artificially created negative-strand RNA virus, including measles and influenza viruses, is based on the principles of Klaus’s technique. His deep interest in fundamental molecular mechanisms led him to investigate the assembly of rabies virus, demonstrating that virion budding could occur with core structural components alone and independently of the glycoprotein—a key insight published in Cell (1996). These findings informed the rational design of attenuated viral strains and vaccine vectors.
After joining the LMU Munich faculty in 1999, Klaus's research expanded into the molecular mechanisms underlying virus–host interactions. A defining moment in innate immunity research came in 2006, when Klaus co-authored a Science paper together with one of us (VH), demonstrating how cells discriminate viral RNA from self. My (VH) first contact with Klaus was as a young research associate, when I reached out to him for his virology expertise. I had a question about a reagent, and since it was the summer holiday season, I wasn’t expecting much of a response—especially after receiving an out-of-office reply. But it didn’t take long before Klaus got in touch—while still on vacation, I believe in Italy—and immediately offered his help. That generous gesture marked the beginning of what became a rewarding collaboration. We worked together to understand how viruses are sensed by innate immune cells, a field still emerging in the mid-2000s. At the time, there was only a hunch that cytosolic RNA sensing pathways existed, but the molecular players remained elusive. With the discovery of RIG-I by the Fujita lab in 2004, we finally had a clearer idea of where to look. Following our discovery that triphosphate RNA is a highly potent agonist for RIG-I, we were eager to connect this finding to the recognition of viruses in the cytosol—and Klaus immediately supported us by providing RNA from virus-infected cells to test our hypothesis. The resulting study resonated widely in the field and quickly became a foundational reference for understanding viral RNA sensing—something we could not have achieved without Klaus’s early and enthusiastic support.
Prior to this publication, I (KPH) vividly remember how Klaus, all secretive, came to my office just as we were beginning work on RIG-I structures. He told me that he and his collaborators had figured out how RIG-I can discriminate self from non-self. But, with a boyish smile, he continued that “unfortunately, he can’t really tell me any details”. He kindly agreed to a little guessing game—the outcome of which I’ll leave open here. In any case, the mechanism was officially revealed shortly thereafter in Science (2006), where Klaus and we (VH and the team around Gunther Hartmann and Stefan Endres) showed that uncapped 5′-triphosphate RNA is the natural ligand for the cytosolic receptor RIG-I to discriminate self from non-self RNA. Klaus's expertise in virology was instrumental in generating the defined viral RNA species and engineered viruses used in these studies.
Following this line of research, Klaus’s lab revealed viral immune evasion strategies across multiple pathogens, including rabies virus, measles virus, and respiratory syncytial virus—helping to explain how these viruses establish infection in humans. His favorite protein of the rabies virus was the P protein, now recognized as one of the strongest viral antagonists of human interferon responses. Another favorite of his was the V protein, which antagonizes MDA5-based RNA sensing. With his great enthusiasm, he incited us (KPH) and then collaborated to reveal its structural mechanism (Science, 2013).
On a clear day in early 2020, in the wake of the COVID-19 pandemic, I (KS) visited Klaus in an almost deserted Gene Center. Though physically distanced, we intensely discussed a novel emerging virus—SARS-CoV-2—and how we, as virologists, could help to combat this threat. These discussions sparked a series of interdisciplinary studies that clarified immune evasion strategies mediated by individual SARS-CoV-2 proteins (Science, 2020; Cell Reports, 2021). Klaus’s lab also applied his viral engineering expertise to vaccine development against SARS-CoV-2. His group created replication-deficient rhabdovirus replicons expressing heterologous antigens—a platform that enabled the development of a chimeric VSV/rabies vector presenting a SARS-CoV-2 minispike, which elicited robust neutralizing antibody responses in preclinical models (PLOS Pathogens, 2021). These works highlight Klaus's engagement with pressing biomedical challenges and his astonishing ability to flexibly apply his expertise to emerging threats.
Among Klaus's most transformative contributions was the engineering of glycoprotein-deleted rabies virus vectors for trans-synaptic tracing of neuronal circuits. In a stroke of genius, he and his collaborating neuroscientists recognized the potential of the exclusively synaptic spread of rabies virus for mapping the connectome of neurons in the brain. Together with his team and collaborators, Klaus developed recombinant rabies viruses capable of monosynaptic spread, enabling cell-type-specific mapping of neuronal inputs. These systems, described in Neuron and Nature Methods (2007), became cornerstone tools in systems neuroscience. This work highlights the power of interdisciplinary basic science to enable transformative technologies that reshape entire fields. Klaus's lab continued to refine these vectors, expanding their application to studies of pain, emotion, and behavior in animal models. His innovations provided unprecedented access to the architecture of neural circuits and remain essential in contemporary neurobiological research. Klaus Conzelmann’s trans-synaptic tracing of neuronal circuits through engineered rabies viruses stands among the Gene Center's most significant contributions to technology.
Klaus was a highly sought-after and active participant in many collaborative research initiatives spanning virology, innate immunity, and neurobiology. He contributed extensively to the scientific community through editorial service, peer mentorship, and interdisciplinary collaboration. He was an excellent teacher and supervisor, and I (KS) heard many times that his lectures at the Faculty of Chemistry and Pharmacy even transformed biology-skeptical chemistry students into passionate molecular virologists. Klaus guided many students to their PhDs and remained a friend and mentor to them thereafter.
We will remember Klaus as an extraordinary scientist, rigorous discussion partner, and inspiring mentor. He remained deeply curious about developments in virology, innate immunity, neurobiology and beyond, and his enthusiasm for science never waned. We will always remember the spark in his eyes whenever we exchanged ideas—he had a way of engaging with science that was both rigorous and joyful. Klaus also had a wonderful sense of perspective. There was often a twinkle in his eye and an easy smile—a lightness that made conversations with him a pleasure. In a world that often takes itself too seriously, Klaus brought light, laughter, and sincerity. His spirit left a mark on all of us—and his memory will stay with us always
He will be deeply missed.
Karl-Peter Hopfner
Veit Hornung
Konstantin Sparrer
Munich, April 4th 2025