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* The emergence and evolution of the novel epidemic norovirus GII.4 variant Sydney 2012 Keywords: Norovirus Gastroenteritis Emergence Evolution Sydney 2012 1.Norovirus is the leading cause of acute gastroenteritis with most infections caused by GII.4 variants. 2. To understand the evolutionary processes that contribute to the emergence of GII.4 variants, we examined the molecular epidemiology of norovirus-associated acute gastroenteritis in Australia and New Zealand from 893 outbreaks between 2009 and 2012. 3. Throughout the study GII.4 New Orleans 2009 was predominant; however, during 2012 it was replaced by an emergent GII.4 variant, Sydney 2012 4. An evolutionary analysis of capsid gene sequences was performed to determine the origins and selective pressures driving the emergence of these recently circulating GII.4 variants. 5. This revealed that both New Orleans 2009 and Sydney 2012 share a common ancestor with GII.4 Apeldoorn 2007. 6. Furthermore, preepidemic ancestral variants of each virus were identified up to two years before their pandemic emergence. 7. Adaptive changes at known blockade epitopes in the viral capsid were also identified that likely contributed to their emergence. abstract Introduction New Orleans 2009 and Sydney 2012 share a common ancestor with GII.4 Apeldoorn 2007 1.Overall, 32 variable positions in the GII.4 capsid sequence were identified whe comparing the GII.4 variants of the Apeldoorn lineage, that is, Apeldoorn 2007, Orange 2008, New Orleans 2009,Auckland 2010 and Sydney 2012. These variable sites mostlylocalised to the external surface of the capsidprotein . 2. Importantly, four of these sites, amino acid positions 294, 368, 373 and 376 , were found to be under significant positive selection using all three methods employed–iFEL, FUBAR and MEME. The dN/dS values were 3.40, 3.60, 1.61 and 3.30 for positions 294, 368, 373 and 376, respectiv
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