The emergence and evolution of the novel epidemic norovirus GII.4 variant Sydney 2012

- Thorough surveillance of NoV activity between 2009 and 2012 in Australia and New Zealand was completed.
- The emergent GII.4 Sydney 2012, replaced New Orleans 2009 as the predominant NoV in circulation.
- Pre-epidemic ancestral forms of pandemic viruses were identified 2 years before their emergence.
- Adaptive changes in the viral capsid likely contributed to the emergence of Sydney 2012.

Norovirus is the leading cause of acute gastroenteritis with most infections caused by GII.4 variants. 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. Throughout the study GII.4 New Orleans 2009 was predominant; however, during 2012 it was replaced by an emergent GII.4 variant, Sydney 2012. 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. This revealed that both New Orleans 2009 and Sydney 2012 share a common ancestor with GII.4 Apeldoorn 2007. Furthermore, pre-epidemic ancestral variants of each virus were identified up to two years before their pandemic emergence. Adaptive changes at known blockade epitopes in the viral capsid were also identified that likely contributed to their emergence.