ABSTRACT
The interaction of the rubella virus (RV) capsid (C) protein and the mitochondrial p32 protein is believed to participate in virus replication. In this study, the physiological significance of the association of RV with mitochondria was investigated by silencing p32 through RNA interference. It was demonstrated that downregulation of p32 interferes with microtubule-directed redistribution of mitochondria in RV-infected cells. However, the association of the viral C protein with mitochondria was not affected. When cell lines either pretreated with respiratory chain inhibitors or cultivated under (mild) hypoxic conditions were infected with RV, viral replication was reduced in a time-dependent fashion. Additionally, RV infection induces increased activity of mitochondrial electron transport chain complex III, which was associated with an increase in the mitochondrial membrane potential. These effects are outstanding among the examples of mitochondrial alterations caused by viruses. In contrast to the preferential localization of p32 to the mitochondrial matrix in most cell lines, RV-permissive cell lines were characterized by an almost exclusive membrane association of p32. Conceivably, this contributes to p32 function(s) during RV replication. The data presented suggest that p32 fulfills an essential function for RV replication in directing trafficking of mitochondria near sites of viral replication to meet the energy demands of the virus.
Subject(s)
Host-Pathogen Interactions , Microtubules/metabolism , Mitochondria/metabolism , Mitochondria/virology , Mitochondrial Proteins/metabolism , Rubella virus/pathogenicity , Viral Core Proteins/metabolism , Animals , Carrier Proteins , Cell Line , Electron Transport , Gene Silencing , Humans , Membrane Potential, Mitochondrial , Mitochondrial Proteins/antagonists & inhibitors , RNA InterferenceABSTRACT
A prospective comparison of peritoneal dialysis to hemodialysis was undertaken to identify advantages and disadvantages of either treatment relative to the other. Hematologic, biochemical, lipid, and neurobehavioral parameters were followed. Careful controls were imposed to assure that the treatment groups were comparable. Patients on peritoneal dialysis proved to have more normal concentrations of BUN, hemoglobin, potassium, bicarbonate, and high-density lipoproteins. Hemodialysis patients had more normal concentrations of albumin, total protein, and calcium. Hypertriglyceridemia was only minimally greater in peritoneal patients. Neurobehavioral results documented multiple abnormalities in both. The profile of results obtained provides preliminary criteria for selecting either form of dialysis for a particular patient.
