Epizootic activity of Murray Valley encephalitis and Kunjin viruses in an aboriginal community in the Southeast Kimberley region of Western Australia: Results of mosquito fauna and virus isolation studies

We undertook annual surveys of flavivirus virus activity in the community of Billiluna of Western Australia in the southeast Kimberley region between 1989 and 2001. Culex annulirostris was the dominant mosquito species, particularly in years of above average rains and flooding. Murray Valley encephalitis (MVE) virus was isolated in 8 of the 13 years of the study from seven mosquito species, but more than 90% of the isolates were from Cx. annulirostris. The results suggest that MVE virus is epizootic in the region, with activity only apparent in years with average or above average rainfall and increased numbers of Cx. annulirostris. High levels of MVE virus activity and associated human cases were detected only once (in 1993) during the survey period. Activity of MVE virus could only be partially correlated with wet season rainfall and flooding, suggesting that a number of other factors must also be considered to accurately predict MVE virus activity at such communities.

Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency

Glucocorticoids are pivotal for adipose tissue development. Rodent studies suggest that corticosteroid-binding globulin (CBG) modulates glucocorticoid action in adipose tissue. In humans, both genetic CBG deficiency and suppressed CBG concentrations in hyperinsulinemic states are associated with obesity. We hypothesized that CBG deficiency in humans modulates the response of human preadipocytes to glucocorticoids, predisposing them to obesity. We compared normal preadipocytes with subcultured preadipocytes from an individual with the first ever described complete deficiency of CBG due to a homozygous null mutation. CBG-negative preadipocytes proliferated more rapidly and showed greater peroxisome proliferator-activated receptor-gamma-mediated differentiation than normal preadipocytes. CBG was not expressed in normal human preadipocytes. Glucocorticoid receptor number and binding characteristics and 11beta-hydroxysteroid dehydrogenase activity were similar for CBG-negative and normal preadipocytes. We propose that the increased proliferation and enhanced differentiation of CBG-negative preadipocytes may promote adipose tissue deposition and explain the obesity seen in individuals with genetic CBG deficiency. Furthermore, these observations may be relevant to obesity occurring with suppressed CBG concentrations associated with hyperinsulinemia.

Distribution of Sugarcane mosaic virus in sugarcane plants

Variation in the concentration of virus in different parts of the plant has implications for virus-indexing programs. To allow more reliable detection of Sugarcane mosaic virus (SCMV), the distribution of the virus in sugarcane plants after artificial inoculation was studied using a reverse transcription polymerase chain reaction (RT-PCR) assay. Leaves of susceptible and moderately resistant sugarcane were mechanically inoculated with SCMV 6 weeks after planting. Weekly for 8 weeks after inoculation, plants were examined for mosaic symptoms and samples of leaves, roots and tillers were tested by RT-PCR to detect virus. SCMV moved from the point of inoculation to younger leaves, roots and tillers and eventually to leaves that emerged prior to inoculation. The pattern of SCMV distribution in moderately resistant and susceptible cultivars was not substantially different. However, the virus moved more slowly in the moderately resistant than in the susceptible cultivar. Young leaves proved to be the most suitable tissue for testing.

Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors. (C) 2003 Elsevier Science (USA). All rights reserved.