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Characterization of Norovirus strains and a seroprevalence study to understand the fluctuation of outbreak activity in Alberta, Canada Open Access


Other title
molecular epidemiology
next generation sequencing
RNA virus
transplant patients
Type of item
Degree grantor
University of Alberta
Author or creator
Hasing Rodriguez, Maria E
Supervisor and department
Pang, Xiaoli (Laboratory Medicine and Pathology)
Hazes, Bart (Medical Microbiology and Immunology)
Examining committee member and department
Lee, Bonita (Pediatrics)
Preiksaitis, Jutta (Medicine)
Robinson, Joan (Pediatrics)
Koopmans, Marion (Virology)
Medical Sciences-Laboratory Medicine and Pathology

Date accepted
Graduation date
2016-06:Fall 2016
Doctor of Philosophy
Degree level
Norovirus (NoV) is recognized as the leading agent causing gastroenteritis among individuals of all ages. Historical data of NoV outbreak surveillance in Alberta, Canada, from the period July 2000 to June 2008 demonstrated a biennial pattern of NoV outbreak activity, in which peaks of high outbreak activity appeared to be driven by the emergence of new phylogenetic clusters of NoV within genotype GII.4 (GII.4 variants). The work in this thesis aimed to analyze the outbreak activity of NoV in Alberta between July 2008 and June 2015 and examine novel NoV GII.4 variants as well as immune responses at the population level. Norovirus outbreak surveillance data since July 2008, showed that GII.4 continued to be the most predominant genotype in Alberta, and was responsible for 47.6% to 80.2% of all NoV outbreaks per year. The overall number of NoV outbreaks observed per year demonstrated a loss of the biennial pattern since July 2011 as well as a gradual decline in the number of NoV outbreaks. Two novel GII.4 variants emerged in the 7-year period, New Orleans 2009 and Sydney 2012. Genotype GII.17 was also detected in November 2014. Unlike previous years, peaks of high outbreak activity were not always associated with the emergence of novel GII.4 variants, suggesting that, in addition to antigenic change of NoV GII.4, other factors also contributed to the high levels of NoV outbreak activity in Alberta. Since NoV strain genotyping for outbreak surveillance in the province has been performed based on a small 320bp region within the major capsid gene (ORF2) that provides limited information about the genetic diversity of NoV, a near-full length genome characterization was performed on a group of NoV strains representing 7 different GII.4 variants that have circulated in the province since 2002. A phylogenetic comparison demonstrated that most of the strains found in Alberta were similar to strains that had been described in global pandemics. Furthermore, recombination detection analysis as well as an assessment of the intra-host genetic diversity of NoV during chronic infection suggested that genetic changes in other genes besides the major capsid gene (ORF2), such as p22 (ORF1) and VP2 (ORF3) might improve the fitness of NoV GII.4. In order to examine if waning of herd immune response over time could be a factor in the annual fluctuations of outbreak activity levels, archived sera collected in 2008 and 2012-2014 from two different populations of Alberta, pregnant women and individuals receiving virology-serology testing, were tested for anti-NoV GII.4 IgG in a cross-sectional study. A high seroprevalence of 84.2% and 76.7%, respectively, were observed in each group. No significant differences in prevalence or geometric mean titers were identified across time points in these populations. In summary, the findings from this study suggest that, in addition to antigenic change of NoV at ORF2, other factors also affect the outbreak activity in Alberta and that ORF1 and ORF3 phylogenetic analysis should be included while monitoring the evolution of pandemic NoV strains. The results from this study provide useful data regarding the seroprevalence of NoV GII.4 in Alberta and the variability of anti-NoV GII.4 IgG responses within a large group of individuals, including pregnant women, providing a framework for further studies of immune responses at the population level.
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
Citation for previous publication
Hasing ME, Hazes B, Lee BE, Preiksaitis JK, Pang XL. Analysis of the intra-host genetic diversity of norovirus in patients with acute and chronic infection using next generation sequencing. BMC Genomics. 2016 Jul;17:480.Hasing ME, Hazes B, Lee BE, Preiksaitis JK, Pang XL. Detection and analysis of recombination in GII.4 norovirus strains causing gastroenteritis outbreaks in Alberta. Infect Genet Evol. 2014 Oct;27:181-92.Hasing ME, Lee BE, Preiksaitis JK, Tellier R, Honish L, Senthilselvan A, Pang XL. Emergence of a New Norovirus GII.4 Variant and Changes in the Historical Biennial Pattern of Norovirus Outbreak Activity in Alberta, Canada, from 2008 to 2013. J Clin Microbiol. 2013 Jul;51(7):2204-11.

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