Institute of Virology

Research Interests:

Duxdrugs – Development of DUX4-inhibitors for therapy of herpesviral infections

 

Herpesviridae are DNA viruses that can cause a variety of diseases in humans and animals. The family comprises nine human members, which are further classified into the three subfamilies of alpha-, beta- and gamma-herpes viruses. One hallmark of herpesviruses is the lifetime persistence in the infected host. The persistent viruses are normally controlled by the immune system to remain silent. Upon weakening of the immune system herpesviruses can reactivate and cause symptoms, which is associated with significant morbidity and mortality. As the variety of antiviral drugs is quite limited and resistance mutations arise fequently there is an urgent need for broad-acting antivirals that can be used to treat herpesviral infection and reactivation.

We previously found that the germline transcription factor DUX4 is induced upon herpesviral infection. DUX4 is critical for a process during the early embryonic development, called zygotic genome activation. After the expression in the early development, DUX4 is normally silenced. The ectopic expression of DUX4 by herpesviruses induces a transcriptional program that is essential for herpesviral replication.

Our current research is focused on the rational design of novel anti-herpesviral drugs targeting DUX4. We attempt to identify an inhibitor of DUX4 that can prevent herpesviral zygotic genome activation and therefore can act against herpesviruses of all subfamilies. Simultaneously, we investigate the detailed mechanisms of DUX4 induction upon herpesviral infection.

 

Collaboration Partners:

• Dr. Emanuel Wyler and Dr. Vedran Franke (Berlin Institute of Medical Systems Biology, Berlin, Germany)
• Dr. Alexander Hahn (DPZ, Göttingen, Germany)
• Prof. Dr. Thomas Stamminger (Ulm, Germany)
• Prof. Dr. Armin Ensser (Erlangen, Germany)
• Prof. Dr. Thomas Gramberg (Erlangen, Germany)

 

Team Leader

Dr. rer. nat. Florian Full

Phone: +49 (0)761 203-6587

 

 

Current lab members:

Tatjana Gremelspacher (B.Sc. student, HiWi)

Eva Neugebauer, M.Sc. (Ph.D. student, phone -6607)

Melanie Anna Schächtle, M.Sc. (Ph.D. student, phone -6617)

Jiang Tan, Ph.D (Postdoc, phone -6617)

Pia Veratti, B.Sc. (Technician, phone -6617)

Isabelle Welker (Med student, phone -6607)

 

Selected Publications:
Walter S, Franke V, Drayman N, Wyler E, Tay S, Landthaler M, Akalin A, Ensser A and

Full F. (2021) Herpesviral induction of germline transcription factor DUX4 is critical for

viral gene expression. BioRxiv https://doi.org/10.1101/2021.03.24.436599

 

Full F, Ensser A. (2019) Early Nuclear Events after Herpesviral Infection. J Clin Med. 2019

Sep 7;8(9). pii: E1408. doi: 10.3390/jcm8091408. Review

 

Full F, van Gent M, Sparrer KMJ, Chiang C, Zurenski MA, Scherer M, Brockmeyer NH,

Heinzerling L, Stürzl M, Korn K, Stamminger T, Ensser A and Gack MU. (2019)

Centrosomal protein TRIM43 restricts herpesvirus infection by regulating nuclear

lamina integrity. Nature Microbiology, 2019 Jan;4(1):164-176.

 

Full F, Jungnickl D, Reuter N, Bogner E, Brulois K, Scholz B, Stürzl M, Myoung J, Jung JU,

Stamminger T, Ensser A. (2014) Kaposi's sarcoma associated herpesvirus tegument

protein ORF75 is essential for viral lytic replication and plays a critical role in the

antagonization of ND10-instituted intrinsic immunity. PLoS Pathog. 10(1):e1003863.