The molecular epidemiology of norovirus outbreaks in Victoria, 2014 to 2015
.

Noroviruses are a leading cause of outbreaks of gastroenteritis. This study examined the incidence and molecular characteristics of norovirus outbreaks in healthcare and non-healthcare settings in Victoria, Australia, over 2 years (2014-2015). Norovirus was detected in 65.7% and 60.4% of gastroenteritis outbreaks investigated for the years 2014 and 2015 respectively. There was a significant decline in the number of norovirus outbreaks in the period 2014 to 2015 although in both years norovirus outbreaks peaked in the latter part of the year. Norovirus Open Reading Frame (ORF) 2 (capsid) genotypes identified included GI.2, GI.3, GI.4, GI.5, GI.6, GI.9, GII.2, GII.3, GII.4, GII.6, GII.7, GII.8, GII.13 and GII.17. GII.4 was the most common genotype detected. In addition, the following ORF 1/ORF 2 recombinant forms were confirmed: GII.P4_NewOrleans_2009/GII.4_Sydney_2012, GII.P12/GII.3, GII.Pb (GII.21)/GII.3, GII.Pe/GII.2 and GII.Pe/GII.4_Sydney_2012. A significant decline was noted in the chief norovirus strain GII.Pe/GII.4_Sydney_2012 between 2014 and 2015 but there was a re-emergence of a GII.P4_ NewOrleans _2009 norovirus strain. Outbreaks involving the GII.P17/GII.17 genotype were also detected for the first time in Victoria. GI genotypes circulating in Victoria for the 2 years 2014 and 2015 underwent a dramatic change between the 2 years of the survey. Many genotypes could occur in both healthcare and non-healthcare settings although GI.3, GII.6, and GII.4 were significantly more common in healthcare settings. The study emphasises the complex way in which norovirus circulates throughout the community.

The Comparative Molecular Epidemiology of GII.P7_GII.6 and GII.P7_GII.7 Norovirus Outbreaks in Victoria, Australia, 2012-2014.

The comparative molecular epidemiology of the related GII.P7_GII.6 and GII.P7_GII.7 noroviruses has not been examined in detail. ORF 1, ORF 2 and ORF 1/ORF 2 RT-PCR as well as sequencing and phylogeny analysis were carried out on faecal specimens from 873 gastroenteritis outbreaks in Victoria, Australia (2012-2014). There were 575 (66%) detected as positive for norovirus by means of ORF 1 RT-PCR and/or ORF 2 RT-PCR. Of these, 24 (4.2%) were GII.6 (ORF 2) outbreaks, 7 (1.2%) were GII.7 (ORF 2) outbreaks, and 1 outbreak (0.2%) involved both GII.6 (ORF 2) and GII.7 (ORF 2) noroviruses. The median age of patients identified with GII.6 (ORF 2) (84 years) was significantly different from that of patients identified with GII.7 (ORF 2) (39 years). ORF 2 GII.6 and ORF 2 GII.7 sequences were always associated with a GII.P7 ORF 1 sequence, and GII.P7 sequences fell into two clusters, with one corresponding to the GII.6 ORF 2 genotype and the other to the GII.7 ORF 2 genotype, thereby indicating that the ORF 1 has been evolving separately for the two viruses. Thus, two closely related noroviruses can have a markedly different incidence and epidemiology.

The Central Role of Wnt Signaling and Organoid Technology in Personalizing Anticancer Therapy.

The Wnt pathway is at the heart of organoid technology, which is set to revolutionize the cancer field. We can now predetermine a patient's response to any given anticancer therapy by exposing tumor organoids established from the patient's own tumor. This cutting-edge biomedical platform translates to patients being treated with the correct drug at the correct dose from the outset, a truly personalized and precise medical approach. A high throughput drug screen on organoids also allows drugs to be tested in limitless combinations. More recently, the tumor cells that are resistant to the therapy given to a patient were selected in culture using the patient's organoids. The resistant tumor organoids were then screened empirically to identify drugs that will kill the resistant cells. This information allows diagnosis in real-time to either prevent tumor recurrence or effectively treat the recurring tumor. Furthermore, the ability to culture stem cell-derived epithelium as organoids has enabled us to begin to understand how a stem cell becomes a cancer cell or to pin-point the genetic alteration that underlies a given genetic syndrome. Here we summarize these advances and the central role of Wnt signaling, and identify the next challenges for organoid technology.

Evolutionary changes in the capsid P2 region of Australian strains of the norovirus GII.Pe_GII.4.

PURPOSE: The protruding (P) 2 region of the norovirus capsid is thought to include hypervariable sites involved in receptor binding. This study examines the changes that occurred in the P2 region of GII.Pe_GII.4 norovirus in the course of its evolution from a precursor phase (2008-2009), to an intermediate phase (2010) and finally to an epidemic phase (2012-2015). METHODOLOGY: Twenty-two P2 region amino acid (aa) sequences (166 aa long) from all phases of the evolution of the virus were compared and the changes analysed.Results/key findings. Twenty sites in the P2 region underwent aa change and of these, 10 corresponded to previously proposed hypervariable sites and 10 to novel hypervariable sites. It was notable that aa changes at two sites, X and Y, only emerged as the epidemic phase progressed. 3D computer modelling of the P2 region indicated that neither X nor Y were in the uppermost 'crown', but further down in the 'neck' portion. The location of X and Y and the nature of aa change at Y suggest these sites were important in enhancing the structural integrity of the capsid, which in turn may have facilitated the longer term viability of the virus. CONCLUSION: The current study helps establish the validity of previously proposed hypervariable sites in the P2 region as well as indicating new ones. It also provides quantitative and qualitative data on how these sites changed over the evolutionary history of a particular norovirus strain.