The Role of Viral Population Diversity in Adaptation of Bovine Coronavirus to New Host Environments

The high mutation rate of RNA viruses enables a diverse genetic population of viral genotypes to exist within a single infected host. In-host genetic diversity could better position the virus population to respond and adapt to a diverse array of selective pressures such as host-switching events. Multiple new coronaviruses, including SARS, have been identified in human samples just within the last ten years, demonstrating the potential of coronaviruses as emergent human pathogens. Deep sequencing was used to characterize genomic changes in coronavirus quasispecies during simulated host-switching. Three bovine nasal samples infected with bovine coronavirus were used to infect human and bovine macrophage and lung cell lines. The virus reproduced relatively well in macrophages, but the lung cell lines were not infected efficiently enough to allow passage of non lab-adapted samples. Approximately 12 kb of the genome was amplified before and after passage and sequenced at average coverages of nearly 950×(454 sequencing) and 38,000×(Illumina). The consensus sequence of many of the passaged samples had a 12 nucleotide insert in the consensus sequence of the spike gene, and multiple point mutations were associated with the presence of the insert. Deep sequencing revealed that the insert was present but very rare in the unpassaged samples and could quickly shift to dominate the population when placed in a different environment. The insert coded for three arginine residues, occurred in a region associated with fusion entry into host cells, and may allow infection of new cell types via heparin sulfate binding. Analysis of the deep sequencing data indicated that two distinct genotypes circulated at different frequency levels in each sample, and support the hypothesis that the mutations present in passaged strains were “selected” from a pre-existing pool rather than through de novo mutation and subsequent population fixation.     

Cancer incidence and mortality in people aged less than 75 years: Changes in Australia over the period 1987–2007

BackgroundAustralia has one of the highest rates of cancer incidence worldwide and, despite improving survival, cancer continues to be a major public health problem. Our aim was to provide simple summary measures of changes in cancer mortality and incidence in Australia so that progress and areas for improvement in cancer control can be identified.MethodsWe used national data on cancer deaths and newly registered cancer cases and compared expected and observed numbers of deaths and cases diagnosed in 2007. The expected numbers were obtained by applying 1987 age–sex specific rates (average of 1986–1988) directly to the 2007 population. The observed numbers of deaths and incident cases were calculated for 2007 (average of 2006–2008). We limited the analyses to people aged less than 75 years.ResultsThere was a 28% fall in cancer mortality (7827 fewer deaths in 2007 vs. 1987) and a 21% increase in new cancer diagnoses (13,012 more diagnosed cases in 2007). The greatest reductions in deaths were for cancers of the lung in males (?2259), bowel (?1797), breast (?773) and stomach (?577). Other notable falls were for cancers of the prostate (?295), cervix (?242) and non-Hodgkin lymphoma (?240). Only small or no changes occurred in mortality for cancers of the lung (female only), pancreas, brain and related, oesophagus and thyroid, with an increase in liver cancer (267). Cancer types that showed the greatest increase in incident cases were cancers of the prostate (10,245), breast (2736), other cancers (1353), melanoma (1138) and thyroid (1107), while falls were seen for cancers of the lung (?1705), bladder (?1110) and unknown primary (?904).ConclusionsThe reduction in mortality indicates that prevention strategies, improvements in cancer treatment, and screening programmes have made significant contributions to cancer control in Australia since 1987. The rise in incidence is partly due to diagnoses being brought forward by technological improvements and increased coverage of screening and early diagnostic testing.     

Legionella pneumophila Effector RomA Uniquely Modifies Host Chromatin to Repress Gene Expression and Promote Intracellular Bacterial Replication

1. Download : Download high-res image (266KB)
2. Download : Download full-size image

Highlights? Upon infection, L. pneumophila secretes RomA, a SET domain-containing methyltransferase ? RomA triggers H3K14 trimethylation, causing a switch from gene activation to repression ? ChIP-seq identified 4,870 H3K14 methylated promoter regions, including innate immune genes ? RomA SET domain is required for efficient intracellular replication of L. pneumophila     

The Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative Escherichia coli Infection

Background

Enteroaggregative Escherichia coli (EAEC) is recognized as an emerging cause of persistent diarrhea and enteric disease worldwide. Mucosal immunity towards EAEC infections is incompletely understood due in part to the lack of appropriate animal models. This study presents a new mouse model and investigates the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the modulation of host responses to EAEC in nourished and malnourished mice.

Methods/Principal Findings

Wild-type and T cell-specific PPARγ null C57BL/6 mice were fed protein-deficient diets at weaning and challenged with 5×10⁹cfu EAEC strain JM221 to measure colonic gene expression and immune responses to EAEC. Antigen-specific responses to E. coli antigens were measured in nourished and malnourished mice following infection and demonstrated the immunosuppressive effects of malnutrition at the cellular level. At the molecular level, both pharmacological blockade and deletion of PPARγ in T cells resulted in upregulation of TGF-β, IL-6, IL-17 and anti-microbial peptides, enhanced Th17 responses, fewer colonic lesions, faster clearance of EAEC, and improved recovery. The beneficial effects of PPARγ blockade on weight loss and EAEC clearance were abrogated by neutralizing IL-17 in vivo.

Conclusions

Our studies provide in vivo evidence supporting the beneficial role of mucosal innate and effector T cell responses on EAEC burden and suggest pharmacological blockade of PPARγ as a novel therapeutic intervention for EAEC infection.     

Effect of Game Management on Wild Red-Legged Partridge Abundance

The reduction of game and fish populations has increased investment in management practices. Hunting and fishing managers use several tools to maximize harvest. Managers need to know the impact their management has on wild populations. This issue is especially important to improve management efficacy and biodiversity conservation. We used questionnaires and field bird surveys in 48 hunting estates to assess whether red-legged partridge Alectoris rufa young/adult ratio and summer abundance were related to the intensity of management (provision of supplementary food and water, predator control and releases of farm-bred partridges), harvest intensity or habitat in Central Spain. We hypothesized that partridge abundance would be higher where management practices were applied more intensively. Variation in young/adult ratio among estates was best explained by habitat, year and some management practices. Density of feeders and water points had a positive relationship with this ratio, while the density of partridges released and magpies controlled were negatively related to it. The variables with greatest relative importance were feeders, releases and year. Variations in post-breeding red-legged partridge abundance among estates were best explained by habitat, year, the same management variables that influenced young/adult ratio, and harvest intensity. Harvest intensity was negatively related to partridge abundance. The other management variables had the same type of relationship with abundance as with young/adult ratio, except magpie control. Variables with greatest relative importance were habitat, feeders, water points, releases and harvest intensity. Our study suggests that management had an overall important effect on post-breeding partridge abundance. However, this effect varied among tools, as some had the desired effect (increase in partridge abundance), whereas others did not or even had a negative relationship (such as release of farm-reared birds) and can be thus considered inefficient or even detrimental. We advise reconsidering their use from both ecological and economical points of view.     

<Emphasis Type="Italic">Bruguiera hainesii</Emphasis>, a critically endangered mangrove species,is a hybrid between <Emphasis Type="Italic">B. cylindrica</Emphasis> and <Emphasis Type="Italic">B. gymnorhiza</Emphasis> (Rhizophoraceae)

Bruguiera hainesii (Rhizophoraceae) is one of the two Critically Endangered mangrove species listed in the IUCN Red List of Threatened Species. Although the species is vulnerable to extinction, its genetic diversity and the evolutionary relationships with other Bruguiera species are not well understood. Also, intermediate morphological characters imply that the species might be of hybrid origin. To clarify the genetic relationship between B. hainesii and other Bruguiera species, we conducted molecular analyses including all six Bruguiera species using DNA sequences of two nuclear genes (CesA and UNK) and three chloroplast regions (intergenic spacer regions of trnL-trnF, trnS-trnG and atpB-rbcL). For nuclear DNA markers, all nine B. hainesii samples from five populations were heterozygous at both loci, with one allele was shared with B. cylindrica, and the other with B. gymnorhiza. For chloroplast DNA markers, the two haplotypes found in B. hainesii were shared only by B. cylindrica. These results suggested that B. hainesii is a hybrid between B. cylindrica as the maternal parent and B. gymnorhiza as the paternal one. Furthermore, chloroplast DNA haplotypes found in B. hainesii suggest that hybridization has occurred independently in regions where the distribution ranges of the parental species meet. As the IUCN Red List of Threatened Species currently excludes hybrids (except for apomictic plant hybrids), the conservation status of B. hainesii should be reconsidered.