1. Molecular surveillance of norovirus and study of the evolutionary mechanisms of antigenic drift and shift
- Author
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Sitabkhan, Alefiya
- Subjects
Antigenic drift ,fluids and secretions ,viruses ,virus diseases ,Antigenic shift ,Norovirus epidemiology - Abstract
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.
- Published
- 2017
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