Herpes viruses is a large group of viruses infecting multicellular organisms ranging from molluscs to man. Herpes viruses cause disease with serious consequences in humans and live-stock and they constitute a threat to endangered species in captivity as well as in the wild. The successful strategy adopted by herpes viruses involves an initial infection followed by establishment of a latent state in the infected individual. At variable intervals the virus may reactivate and cause a productive infection. For this reason most humans carry more than one out of the eight different herpes viruses specific for man. In individuals undergoing immunosuppressive therapy the frequency of reactivation is drastically increased and may lead to life-threatening disease.
Our research is focussed on Herpes simplex virus type I which replicates efficiently in peripheral tissue and establishes latency in neuronal cells. The virus has a 150 kbp double-stranded DNA genome encoding approximately 80 genes. Upon infection the linear genome is delivered to the nucleus and it becomes circular due to the action of DNA ligase IV. The circular genome is replicated by a machine consisting of seven proteins encoded by the virus. This molecular machine, referred to as the replisome, is assembled at specific site on the virus chromosome, the origins of DNA replication. The reaction is dependent on the initiator protein OBP encoded by the UL9 gene. The remaining components of the replisome, the UL30/UL42 DNA polymerase, the UL5/UL8/UL52 helicase-primase and the UL29 single-strand DNA-binding protein (ICP8) perform coupled synthesis of leading and lagging strands thereby generating concatemers of virus genomes which can be processed and encapsidated.
Our current research concerns the structure and assembly of the replisome and how the activated replisome interacts with cellular mechanism for DNA repair, recombination and transcription. We believe that such transactions, which are highly active during a productive infection, must be tightly regulated during establishment of and reactivation from latency. We wish to identify such regulatory mechanisms in order to complete our understanding of the HSV-1 life-cycle at molecular resolution.
Muylaert, I., Tang, K.-W., and Elias, P. (2011) Replication and recombination of herpes simplex virus DNA. J. Biol. Chem. 286, 15619-15624.