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Steven van Beurden

Wednesday 22 August 2012

‘Molecular characterization of the alloherpesvirus anguillid herpesvirus 1’

Promotor: Prof.dr Rottier
Defence: 30 August 2012

All herpesviruses belong to the order Herpesvirales, which consists of the families Herpesviridae, Alloherpesviridae and Malacoherpesviridae. Although herpesviruses share unique morphological characteristics, only the gene encoding the ATPase subunit of terminase is detectably conserved throughout the order. The family Herpesviridae, which comprises mammalian, reptilian and avian herpesviruses, has been studied extensively, but much less knowledge is available for members of the families Alloherpesviridae and Malacoherpesviridae, which respectively comprise amphibian and fish, and invertebrate, herpesviruses. Since only a dozen genes are detectably conserved among fish and amphibian herpesviruses, the family Alloherpesviridae appears to be more divergent than the family Herpesviridae, among which more than 40 genes are conserved. We have studied the genome, transcriptome and proteome of an eel herpesvirus, anguillid herpesvirus 1 (AngHV1), as a model for the family Alloherpesviridae, and have related our findings to the general characteristics of the family Herpesviridae. AngHV1 has a genome of close to 250 kbp, including an 11 kbp terminal direct repeat. High-resolution transcriptome analysis based on deep sequencing revealed that RNA splicing is much more abundant than had been assumed, and this has major consequences for understanding gene content and predicted protein properties. A genome-wide expression study using qPCR showed that gene expression is regulated in a temporal fashion, similar to mammalian herpesviruses. The putative regulatory immediate-early genes of AngHV1 were identified. Mass spectrometric analyses of purified virions showed that, although no convincing sequence homology is apparent between the herpesvirus families for any of the structural proteins, virion composition shows many similarities. In addition, certain viral proteins, such as a putative immuno-modulatory IL-10 homolog, were shown to be acquired independently by different family members during the course of evolution. Overall, despite the virtual absence of detectable genetic similarities, the family Alloherpesviridae resembles the family Herpesviridae in many fundamental aspects.