Norovirus (NoV) is a leading causative agent of non-bacterial gastroenteritis in humans worldwide. NoV is genetically classified into five distinct genogroups in which genogroups I (GI), II, and rarely IV infect humans. Each genogroup is further subdivided into different genotypes. Previous local surveillance studies demonstrated that NoV GII, in particular the genotype 4 (GII/4) strain, is the predominant genogroup circulating in Hong Kong since 2001. Similar epidemiologic observations were also reported in the US, Europe, UK, Australia, and Japan, highlighting the enormous pandemic and epidemic potential of this genogroup. However, explanation for its predominance has been lacking. In this study, we demonstrated that NoV GII, comprised mostly of the GII/4 strain, showed an increased median viral RNA level in fecal specimens which was at least 100-fold higher than that of GI. The high level of viral shedding may confer greater opportunity for transmission of GII strains through the fecal-oral route. We also demonstrated that fecal viral RNA level correlated positively and independently with diarrhea duration in NoV GII/4 infections. The median fecal viral level in patients with protracted (last for ≥4 days) diarrhea was 100-fold higher than that in patients with only limited diarrhea. Longer infectivity period may also confer greater opportunity for virus transmission through the fecal-oral route. Higher chance of transmission may result in more efficient person-to-person transmission and rapid dissemination, maintaining a high level of NoV GII persistence in the community. In summer 2006, a territory-wide gastroenteritis outbreak attributed to NoV has occurred with more than 3,000 cases of laboratory-confirmed NoV infections in Hong Kong. Phylogenetic analysis showed that the virus causing this unprecedented outbreak was a novel NoV GII/4 variant distinct from all previously reported global pandemic and local epidemic strains. In this 2006 variant, we identified two hypervariable regions when compared with previous local epidemic strains in 2005: protruding domain 2 (P2 domain) of viral protein 1 (VP1) and VP1-binding domain of VP2. We mapped frequent amino acid substitutions to the modeled antigenic loop regions of P2 domain. We also identified in carboxyl-terminus of VP1 an epidemiologically important, putative conformational epitope that alternates between two 3-amino acid signatures during pandemic NoV GII/4 strains evolution since 1995. Our findings reflect the rapid evolution of NoV GII/4 under immunological pressure and suggest that immune evasion might be a potential mechanism for pandemic NoV GII/4 strains emergence. Taken together, high level of fecal viral shedding, longer infectivity period, and periodic emergence of novel variant may underlie the global predominance of NoV GII. Further investigations are warranted to better understand the public health and biological importance of NoV GII. / Chan, Chi Wai. / Adviser: Wai K. Leung. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0818. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 124-143). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / School code: 1307.
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344436 |
| Date | January 2007 |
| Contributors | Chan, Chi Wai Angus., Chinese University of Hong Kong Graduate School. Division of Medical Sciences. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, theses |
| Format | electronic resource, microform, microfiche, 1 online resource (xiv, 147 leaves : ill.) |
| Coverage | China, Hong Kong, Hong Kong |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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