Our Research Profile

The two coordinated program areas (PB) Molecular Mechanisms of Viral Pathogenesis (PB1) and Innovative Antiviral Therapies (PB2) represent the LIV’s research principles and shape its research profile. The program areas highlight the applied aspect of the institute’s basic research in virology in which fundamental mechanisms of viral pathogenesis are to be identified across all virus species. Using the latest technologies and (small animal) infection models, multidisciplinary discoveries are to be converted into therapeutic approaches and tested in preclinical trials.

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Molecular Mechanisms of Viral Pathogenesis
Innovative Antiviral Therapies

Overarching Topics

Another building block in the research profile of the LIV are the internal overarching key topics:

Host Range Determinants
Immune Control of Viruses
Structure and Dynamics of Viral Morphogenesis
Viral Latency and Persistence

The concept of the overarching topics is to bundle the broad virological expertise of the LIV research teams into common questions and to investigate basic, universally valid mechanisms of virus multiplication, pathogenesis and cellular virus defense across laboratories and virus species.

The overarching topics make targeted use of the broad spectrum of virus systems investigated at the LIV, network the LIV program areas and thus sustainably strengthen the research profile of the LIV. In the medium to long term, the concept is intended to promote both the joint acquisition of third-party funds and the transfer of research results into therapeutic approaches and preclinical studies.

Linkage through Viral Data Science

The research field Viral Data Science interlinks the overarching focus topics as well as the technology platforms and scientific computing IT infrastructures of the LIV. It promotes the development of expertise required to address innovative scientific questions in complex biological systems and facilitates the implementation of central approaches for the integrative analysis of systemic data. The term Viral Data Science encompasses all steps involved in extracting knowledge from large amounts of data, from collection, storage and processing to computer-aided interpretation (data mining) of the data using advanced algorithms (machine learning, deep learning). Examples include the systemic analysis of high-dimensional flow cytometry, mass spectrometry and sequence data to correlate immunological parameters with viral evolution and host adaptation, or the linking of genomic and proteomic data sets to investigate geno-phenotype relationships during the pathogenesis of viral diseases.

Chart Focus topics wrapped in technology platforms and viral data science

The four overarching topics in detail

Host Range Determinants

The first overarching topic Host Range Determinants focuses on the joint identification and characterization of determinants of the host spectrum of various human pathogenic viruses (influenza viruses, SARS and MERS coronaviruses, arboviruses, Zika, hepatitis C viruses (HCV) and cytomegaloviruses (CMV)). The aim is to generate a better understanding of cellular restriction mechanisms and viral antagonists during acute and chronic infections in permissive and non-permissive host cells. The different stages of the infection cycle from receptor recognition to virus release as well as the triggered immune response will be investigated. The use of different viruses allows identifying common and differential mechanisms that define the viral host spectrum. Furthermore, we investigate which countermeasures viruses of different species have developed during evolution to break through intracellular host barriers and thus adapt to new hosts. Using the expertise and infrastructure available at LIV, the basic mechanisms and factors with respect to their influence on the pathogenesis in infection models are investigated in detail in the technology platform Small Animal Models.

Immune Control of Viruses

The aim of the second overarching topic Immune Control of Viruses is the development of immunotherapeutic approaches that enhance or newly induce antiviral immune responses. The joint research activities in the overarching topic focus on investigations of cellular factors of intrinsic, innate and adaptive immunity, using various in vitro model systems, including newly established organoid systems, as well as the humanized mouse models developed at the LIV.The third overarching topic, Viral Latency and Persistence, is devoted to research on latent or chronically persistent viruses (e.g. HIV-1, Herpes Simplex Viruses (HSV), Kaposi's Sarcoma Associated Herpes Virus (KSHV), Epstein-Barr Virus (EBV), CMV, Merkel Cell Polyoma Virus (MCPyV), BKV, or HAdV). The formation of viral persistence or latency reservoirs represents a particular challenge in the fight against these infections. The aim is to identify the molecular factors and mechanisms that are responsible for the establishment and control of latent or chronic infections with the help of suitable model systems, to investigate pathogenicity mechanisms of such infections and to develop new methods for eradicating viral reservoirs. In addition to virus-specific factors, the focus of this research area is on mechanisms of viral latency and persistence, e.g. with regard to the epigenetic regulation of viral and cellular chromatin. With these topics, the focus ties in with the research program of the overarching topic Immune Control of Viruses, both with respect to mechanisms of immune evasion during long-term persistence and with respect to virally induced pathogenesis in the immunodeficient host.

Viral Latency and Persistence

The third overarching topic Viral Latency and Persistence, is dedicated to research into latent or chronically persistent viruses (e.g. HIV-1, herpes simplex viruses (HSV), Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV), CMV, Merkel cell polyomavirus (MCPyV), BKV, or HAdV). The formation of viral persistence or latency reservoirs poses a particular challenge in combating these infections. The aim is to use suitable model systems to identify the molecular factors and mechanisms that are responsible for the establishment and control of latent or chronic infections, to investigate the pathogenicity mechanisms of such infections and to develop new methods for the eradication of viral reservoirs. In addition to virus-specific factors, the focus area also examines mechanisms of viral latency and persistence that are important in principle, for example with regard to the epigenetic regulation of viral and cellular chromatin. With these topics, the priority area ties in with the research program of the priority area of immune control of viruses both with regard to mechanisms of immune evasion during long-term persistence and with regard to viral-induced pathogenesis in the immunodeficient host.

Structure and Dynamics of viral Morphogenesis

The fourth overarching topic Structure and Dynamics of viral Morphogenesis deals with the structural changes in the assembly and disassembly of viral particles over time (morphogenesis). The focus is on quantitative approaches and the integration of data over a wide range of spatial and temporal resolution. Using different virus models (e.g. HAdV, HCV, as well as various corona, herpes, noro- and retroviruses), specifics of host interaction will be characterized and cross-species principles derived. Furthermore, the expertise and infrastructure available at the LIV in the field of a broad spectrum of microscopic and mass spectrometric methods will be used and further developed, for example in the field of correlative imaging or the use of novel radiation sources (European XFEL). Dynamic membrane modulations, specific lipid environments of membrane proteins or the influence of glycosylation patterns are further development areas of this overarching topic. A particular strength lies in the combination and integration of complementary data from different techniques, such as electron microscopy and mass spectrometry or molecular modeling, which allow a deeper understanding of the interrelationships.