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SUMMARY:Integration of herpesvirus DNA into host chromosomes - where\, whe
 n and why - Professor Klaus Osterrieder\, Free University\, Berlin
DTSTART:20100422T110000Z
DTEND:20100422T120000Z
UID:TALK23745@talks.cam.ac.uk
CONTACT:Sue Griffin
DESCRIPTION:Research Interests: Our group is interested in the replication
  and pathogenesis of animal herpesviruses such as equine herpesvirus type 
 1 (EHV-1)\, Marek's disease virus (MDV) and varicella zoster virus (VZV). 
 \n\nEquine herpes virus 1 (EHV-1) Immunomodulatory proteins: Our aim is to
  evaluate the role of EHV-1 glycoproteins in the pathogenesis of this viru
 s. Some of these glycoproteins have been shown to have immunomodulatory pr
 operties\, such as glycoprotein G (gG) which binds chemokines with high af
 finity. Furthermore\, the UL49.5 product\, which has TAP inhibitory activi
 ty\, i.e. it prevents transport of proteasome-generated peptides into the 
 ER and thereby their presentation by MHC class molecules. \n\nWe cloned EH
 V-1 isolates as bacterial artificial chromosomes (BAC)\, which we will use
  to make mutants that are either unable to express gG or unable to produce
  its secreted form. The mutant viruses will be tested in vivo for their gr
 owth properties and virulence in the natural host. We will also test the g
 rowth properties of a UL49.5-negative mutant in horses and examine the mol
 ecular mechanism underlying TAP inhibition by the UL49.5 product. \n\nDeve
 lopment of EHV-1 as an immunization and/or gene therapy vector: We investi
 gate the possibilities of using EHV-1 as a vector to deliver foreign genes
  to equines and other mammals\, including humans. We have generated mutant
 s expressing antigens from West Nile virus\, equine and avian influenza vi
 rus\, Venezuelan equine encephalitis virus\, or the human pathogen hepatit
 is C virus. These constructs have already been tested in mice and we plan 
 to administer them to either the target species (animals) or primates for 
 the induction of insert-specific and sustained immune responses. \n\nMarek
 's Disease Virus (MDV) MHC class I down-regulation and production of mutan
 t MDV random mutagenesis: We have identified proteins that may play an imp
 ortant role in MHC class I downregulation\, but we expect several proteins
  to be involved in this targeted interference with the host's immune respo
 nse to infection. We plan at identifying the mechanism underlying this imm
 une evasion mechanism by several different approaches\, including MHC clas
 s I maturation studies and studies of protein-protein interactions. \n\nRo
 le of glycoprotein C (gC) in tumor formation: We were able to show that MD
 V gC is expressed as three different moieties\, one cell associated\, two 
 secreted\, which are generated by a splicing event. The hypothesis to be t
 ested is that gC expression is involved in MDV tumor formation and horizon
 tal virus spread. \n\nRole of telomerase RNA and telomeric repeat sequence
 s in MDV pathogenesis: MDV induces a highly malignant T cell lymphoma in i
 ts primary host\, the chicken. Telomerase performs an important function i
 n the cellular survival program by maintaining the integrity of chromosome
 s through amplification of telomeric repeats. MDV harbors in its genome tw
 o copies of a viral telomerase RNA (vTR)\, which appears to play a direct 
 role in lymphomagenesis and tumor metastasis. Our long-term goal is to elu
 cidate in detail the mechanisms of the tumor-promoting effects of telomera
 se. This natural small animal model of virus-induced lymphoma allows us to
  interfere with telomerase activity by specifically altering the structure
  and/or levels of (v)TR in infected cells. \n\nVaricella zoster virus Gene
 ration of a BACs and preliminary testing of selected mutant viruses: The u
 nderstanding of VZV pathogenesis and the development of novel well-charact
 erized vaccines have been complicated by the difficulties in mutant virus 
 generation. We introduced BAC technology to VZV research and first analyse
 d the structural function of the VZV ORF9 product\, a putative tegument pr
 otein. This protein was shown to be essential for virus growth. In future 
 studies\, we will analyze open reading frames that are involved in immune 
 evasion and localized at genomic termini.
LOCATION:Sackler Lecture Theatre\, Level 7\, CIMR\, Addenbrooke’s Hospit
 al
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