The Human Cytomegalovirus UL76 Gene Regulates the Level of Expression of the UL77 Gene

Human cytomegalovirus (HCMV) can be reactivated under immunosuppressive conditions causing several fatal pneumonitis, hepatitis, retinitis, and gastrointestinal diseases. HCMV also causes deafness and mental retardation in neonates when primary infection has occurred during pregnancy. In the genome of HCMV at least 194 known open reading frames (ORFs) have been predicted, and approximately one-quarter, or 41 ORFs, are required for viral replication in cell culture. In contrast, the majority of the predicted ORFs are nonessential for viral replication in cell culture. However, it is also possible that these ORFs are required for the efficient viral replication in the host. The UL77 gene of HCMV is essential for viral replication and has a role in viral DNA packaging. The function of the upstream UL76 gene in the HCMV-infected cells is not understood. UL76 and UL77 are cistons on the same viral mRNA and a conventional 5' mRNA for UL77 has not been detected. The vast majority of eukaryotic mRNAs are monocistronic, i.e., they encode only a single protein.To determine whether the UL76 ORF affects UL77 gene expression, we mutated UL76 by ORF frame-shifts, stop codons or deletion of the viral gene. The effect on UL77 protein expression was determined by either transfection of expression plasmids or infection with recombinant viruses. Mutation of UL76 ORF significantly increased the level of UL77 protein expression. However, deletion of UL76 upstream of the UL77 ORF had only marginal effects on viral growth.While UL76 is not essential for viral replication, the UL76 ORF is involved in regulation of the level of UL77 protein expression in a manner dependent on the translation re-initiation. UL76 may fine-tune the UL77 expression for the efficient viral replication in the HCMV- infected cells

A case study of physical and social barriers to hygiene and child growth in remote Australian Aboriginal communities

Background\ud Despite Australia's wealth, poor growth is common among Aboriginal children living in remote communities. An important underlying factor for poor growth is the unhygienic state of the living environment in these communities. This study explores the physical and social barriers to achieving safe levels of hygiene for these children.\ud \ud Methods\ud A mixed qualitative and quantitative approach included a community level cross-sectional housing infrastructure survey, focus groups, case studies and key informant interviews in one community.\ud \ud Results\ud We found that a combination of crowding, non-functioning essential housing infrastructure and poor standards of personal and domestic hygiene underlie the high burden of infection experienced by children in this remote community.\ud \ud Conclusion\ud There is a need to address policy and the management of infrastructure, as well as key parenting and childcare practices that allow the high burden of infection among children to persist. The common characteristics of many remote Aboriginal communities in Australia suggest that these findings may be more widely applicable