Search

BackgroundHuman cytomegalovirus (HCMV) is a betaherpesvirus that causes severe disease in situations where the immune system is immature or compromised. HCMV immediate early (IE) gene expression is stimulated by the virion phosphoprotein pp71, encoded by open reading frame (ORF) UL82, and this transactivation activity is important for the efficient initiation of viral replication. It is currently recognized that pp71 acts to overcome cellular intrinsic defences that otherwise block viral IE gene expression, and that interactions of pp71 with the cell proteins Daxx and ATRX are important for this function. A further property of pp71 is the ability to enable prolonged gene expression from quiescent herpes simplex virus type 1 (HSV-1) genomes. Non-human primate cytomegaloviruses encode homologs of pp71, but there is currently no published information that addresses their effects on gene expression and modes of action.ResultsThe UL82 homolog encoded by simian cytomegalovirus (SCMV), strain Colburn, was identified and cloned. This ORF, named S82, was cloned into an HSV-1 vector, as were those from baboon, rhesus monkey and chimpanzee cytomegaloviruses. The use of an HSV-1 vector enabled expression of the UL82 homologs in a range of cell types, and permitted investigation of their abilities to direct prolonged gene expression from quiescent genomes. The results show that all UL82 homologs activate gene expression, and that neither host cell type nor promoter target sequence has major effects on these activities. Surprisingly, the UL82 proteins specified by non-human primate cytomegaloviruses, unlike pp71, did not direct long term expression from quiescent HSV-1 genomes. In addition, significant differences were observed in the intranuclear localization of the UL82 homologs, and in their effects on Daxx. Strikingly, S82 mediated the release of Daxx from nuclear domain 10 substructures much more rapidly than pp71 or the other proteins tested. All UL82 homologs stimulated the early release of ATRX from nuclear domain 10.ConclusionAll of the UL82 homolog proteins analysed activated gene expression, but surprising differences in other aspects of their properties were revealed. The results provide new information on early events in infection with cytomegaloviruses.

This study investigated the views of parents, newborn hearing screeners and Telethon Speech and Hearing (TSH) professionals of the Western Australian Infant Screening for Hearing (WISH) Program. Three questionnaires were used to gather information from the participants. Sixteen responses to the questionnaire were obtained (five parents, five screeners and six TSH professionals) with an additional parent telephoning in her responses. Overall, results showed that families and staff involved in the WISH Program were satisfied with the hearing screening, audiological, early intervention and counselling services provided by the WISH Program and TSH. Recommendations were offered by participants to assist in improving services, as well as continuing the quality of services being offered. Major recommendations were to continue efforts to implement a statewide newborn hearing screening programme in Western Australia, to continue the WISH Program for the private sector, and to make this freely available to parents. Other suggestions included provision of consistent and clear information for parents; an enhanced database system and ongoing data entry; supply of feedback to screeners; and promotion of the WISH Program through improved education of hospital professionals and parents.