Identification of cellular restriction factors against herpesviral infection

• Applicant: Dr. Florian Sebastian Full
• Subject Area: Virology
• Term: from 2012 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 232133718

Members of the TRIpartite Motif (TRIM) protein family of ubiquitin E3-ligases mediate antiviral activities against a variety of different viruses. Whereas some TRIM molecules directly target viral proteins and thus belong to the group of antiviral restriction factors, other TRIM proteins interfere with cellular signaling processes driving viral infection. However, only one TRIM restriction factor has so far been described to act against infections of herpesviruses, which stands in contrast to other viral families. TRIM19/PML was identified to inhibit the replication of various DNA viruses, including herpesviruses. The overall goal of this project is the identification of novel restriction factors against herpesviral infection, in particular infections with the Kaposis Sarcoma-Associated Herpesvirus (KSHV). KSHV belongs to the family of gamma-herpesviruses, and is one of eight human herpesviruses. KSHV is the etiologic agent of three human diseases: Kaposis Sarcoma, a skin tumor of endothelial origin, which is among the leading causes of death in AIDS patients, and two B-cell malignancies, the Primary Effusion Lymphoma and the Multicentric Castleman's Disease.The applicant will screen all human TRIM proteins for KSHV antiviral activity by a combination of different methods. This initial screen will be followed by defining the molecular mechanisms of the most potent restriction factor(s). Moreover, the identified TRIM restriction factor(s) will also be tested for its ability to restrict other members of the human herpesvirus family.The identification of a novel restriction factor against herpesviral infection may define novel molecular targets for therapeutic interventions and ultimatively lead to the development of new therapeutic agents against infections with herpesviruses.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Dr. Michaela Gack