Fachbereich Veterinärmedizin



    Viral factors involved in Marek's disease virus (MDV) genome integration


    Some herpes viruses including Marek’s disease virus (MDV), a highly oncogenic alpha herpes virus, and human herpes virus 6 (HHV-6) integrate their genetic material into host telomeres during the latent stage of infection, which ensures viral genome maintenance in replicating host cells during the quiescent non-productive phase of infection 1, 2. MDV, HHV-6 and several other herpes viruses harbour telomeric repeats (TMRs) identical to host telomere sequences (TTAGGG)n at either end of their linear genomes 3, 4, which suggests a conserved integration mechanism. MDV harbours two sets of such telomeric repeats: a long telomeric repeat region (mTMR) with a variable length of 27 to 100 repeats and a short telomeric repeat region (sTMR) with a fixed number of 6 repeats. We recently demonstrated that the MDV mTMR region is essential for virus genome integration into host telomeres and that integration process is critical for efficient lymphomagenesis, but also for reactivation from the quiescent state of infection. However, the role of the sTMR region in MDV replication and integration remains unknown. Furthermore, MDV and other herpes viruses encode two proteins termed pUL12 and plCP8 that resemble the Red recombination system encoded by bacteriophages such as phage. The pUL12/lCP8 complex is thought to aid the replication of the herpes virus genome, a process requiring homologous recombination events. pUL12 and iCP8 of HSV-1 facilitate recombination in vitro, but the role of pUL12 and iCP8 in MDV replication and especially integration of the virus genome into host chromosomes remains elusive. We hypothesize that the sTMR region at the MDV genomic termini as well as the MDV encoded pUL12/lCP8 recombinases complex facilitates integration of the virus genome into host telomeres. We will test our hypothesis by two specific aims: 1) To determine the role of the sTMR region in MDV replication, integration and disease and tumour development. 2) To test if the MDV pUL12/lCP8 reco

    Projektleitung: Dr. Benedikt Kaufer
    Eintragende Einrichtung: Institut für Virologie
    Projektlaufzeit: 01.09.2011 bis 31.08.2014
    Projekttyp: Forschungsprojekt
    Mittelgeber: DFG - Sachbeihilfe