Program Areas

The two coordinated program areas (PB) Molecular Mechanisms of Viral Pathogenesis (PB1) and Innovative Antiviral Therapies (PB2) represent the HPI’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.

 

Overarching Focus Topics

Another building block in the research profile of the HPI are the internal key topics ‘Determinants of the host spectrum’, ‘Immune control of viruses’, ‘Viral latency’ and ‘Structure and dynamics of viral morphogenesis’.

The concept of the overarching topics is to bundle the broad virological expertise of the HPI 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 HPI, network the HPI program areas and thus sustainably strengthen the research profile of the HPI. 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.

 

Determinants of the host spectrum

Under the first overarching focus topic, projects of several HPI research units will be presented in order to jointly identify and characterize determinants of various human pathogenic viruses (cytomegalovirus (CMV), Kaposi sarcoma-associated herpes virus (KSHV), Epstein-Barr virus (EBV), influenza A virus and HCV). In this context, a better understanding of cellular restriction mechanisms and viral antagonists during chronic latent and acute infections in permissive and non-permissive host cells should be achieved. It also examines which countermeasures viruses of different species have developed in the course of evolution in order to adapt to their new host. Using the expertise available at HPI and the available infrastructure, the mechanisms and factors with regard to their influence on pathogenesis in infection models are examined in detail in the Technology Platform Small Animal Models.

 

Immune control of viruses

The aim of this overarching focus topic is the development of immunotherapeutic approaches that reinforce or re-induce antiviral immune responses. The joint research work on the overarching topic focuses on the investigation of cellular factors of intrinsic and innate immunity in various in vitro model systems and on the humanized mouse models established at HPI as a basis for preclinical studies of various acute and persistent viral infections (Ebola virus, human adenovirus (HAdV), Human CMV, HIV and HCV). In addition, samples from patient cohorts are used to investigate virus-specific and vaccine-induced immune responses. On the basis of this work, the relevance of the findings from in vitro and animal experiments in clinical studies will be validated in the medium term. To test antiviral therapy concepts in pre- and clinical studies on site, conditions will be created in the long term.

 

Viral latency

The third overarching focus topic is devoted to chronic and latent research of persistent viruses such as HIV, herpes simplex virus (HSV), KSHV, EBV or CMV. Its aim is to use suitable model systems to identify factors and mechanisms that are relevant for the establishment and control of latent infections, pathogenic mechanisms during chronic latent infections and to develop new methods of combating chronic and latent infections. In particular, the focus is on the question of which cellular reservoirs of viral latency are formed and which therapeutic options are available for their eradication.

 

Structure and dynamics of viral morphogenesis

The fourth focus topic of the HPI 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 various virus models (including HAdV, EBOV, corona viruses and various herpes, noroviruses and retroviruses), specific features of host interaction are to be characterized and cross-species principles derived. The investigation of critical and comparatively short-lived transition states of basic mechanisms is of particular interest. In addition, HPI's expertise and infrastructures in a broad spectrum of microscopic and mass spectrometric methods will be used and further developed. The basic information obtained in this way is essential for a targeted structure-based drug development.