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Noroviruses (NoVs) cause approximately one-fifth of acute gastroenteritis (AGE) worldwide, with NoV genotype GII.4 causing 70-80% of cases. NoV GII.4 variants have caused six pandemics since 1995 and novel variants emerge every two to three years. The recent pandemic variant, GII.4 Sydney 2012, has been the predominant genotype since 2013. Recently, a previously rare genotype, GII.17, was detected as the dominant genotype in Asia and in sporadic AGE cases around the world. This thesis aimed to evaluate NoV genotype distribution in the Oceania region between 2013 and 2015. Three comprehensive studies were performed in NSW (2014-2015), WA (2013-2014) and NZ (2013-2014). Collated sequence data was used for genotyping, recombination detection and to study capsid antigenic variation. Overall, 391 NoV outbreaks and 205 individual cases were identified in this study. The majority of outbreaks occurred in aged-care facilities (59.3%) followed by commercial food operators (10.9%), childcare centres (9.9%) and hospitals (7.2%). RT-PCR, sequencing and phylogenetic analyses revealed NoV GII.4 Sydney 2012 as the dominant genotype (54.7%-70.4%) in all three regions. Twenty non-GII.4 capsid genotypes were identified including GII.7 (13.8%), GII.6 (12.9%), GI.3 (11.9%) and GII.13 (11.5%). NZ reported majority of the NoV GI strains (94.6%). Co-circulation of different NoV genotypes increases the chances of coinfections and recombination, which is an important mechanism of NoV evolution. Recombination at the ORF1/ORF2 junction facilitates an exchange of non-structural (ORF1) and structural (ORF2) genes that can confer selective advantages on the virus. A total of 21 intergenotypic recombinants and one intragenotype recombinant (GII.P4 New Orleans 2009/GII.4 Sydney 2012) were detected. Two emerging epidemic strains, GII.P16/GII.4 Sydney 2012 and GII.P17/GII.17 were also identified. Variation in the GII.4 capsid sequence has been reported to alter viral antigenicity resulting in immune evasion. VP1 analyses of GII.4 Sydney 2012 (n=26) and GII.17 (n=1) strains showed mutations within the hypervariable P2 domain. These results highlight constant NoV evolution, which requires routine surveillance to effectively track it and predict potential pandemic-causing novel variants. In summary, this thesis described NoV molecular epidemiology in the Oceania region from 2013 to 2015 and explored the dynamic interplay of antigenic drift and shift in NoV evolution.

Norovirus (NoV) is the major cause of acute gastroenteritis across all age groups. In particular, variants of genogroup II, genotype 4 (GII.4) have been associated with epidemics globally, occurring approximately every three years. The pandemic GII.4 variant, Sydney 2012, was first reported in early 2012 and soon became the predominant circulating NoV strain globally. Despite its broad impact, both clinically and economically, our understanding of the fundamental diversity and mechanisms by which new NoV strains emerge remains limited. In this study, we describe the molecular epidemiological trends of NoV-associated acute gastroenteritis in Australia and New Zealand between January 2013 and June 2014.

Norovirus is estimated to cause 677 million annual cases of gastroenteritis worldwide, resulting in 210,000 deaths. As viral gastroenteritis is generally self-limiting, clinical samples for epidemiological studies only partially represent circulating noroviruses in the population and is biased towards severe symptomatic cases. As infected individuals from both symptomatic and asymptomatic cases shed viruses into the sewerage system at a high concentration, waste water samples are useful for the molecular epidemiological analysis of norovirus genotypes at a population level. Using Illumina MiSeq and Sanger sequencing, we surveyed circulating norovirus within Australia and New Zealand, from July 2014 to December 2016. Importantly, norovirus genomic diversity during 2016 was compared between clinical and waste water samples to identify potential pandemic variants, novel recombinant viruses and the timing of their emergence. Although the GII. 4 Sydney 2012 variant was prominent in 2014 and 2015, its prevalence significantly decreased in both clinical and waste water samples over 2016. This was concomitant with the emergence of multiple norovirus strains, including twoGII. 4 Sydney 2012 recombinant viruses, GII. P4 New Orleans 2009/GII.4 Sydney 2012 and GII. P16/GII.4 Sydney 2012, along with three other emerging strains GII. 17, GII. P12/GII.3 and GII. P16/GII.2. This is unusual, as a single GII.4 pandemic variant is generally responsible for 65-80% of all human norovirus infections at any one time and predominates until it is replaced by a new pandemic variant. In sumary, this study demonstrates the combined use of clinical and wastewater samples provides a more complete picture of norovirus circulating within the population.