A Study of Norovirus Molecular Epidemiology: impact, prevalence, diversity and genetic adaptation

Halfway into the past century molecular biology emerged as a science, and it has evolved and grown very rapidly since. As a result of their very nature, infectious diseases have always had the attention of physicians and scientists, and the possibilities for research offered by molecular biology were pre-eminently suitable for studying the causative agents of these infectious diseases, and especially for studying viruses. Noroviruses cause sudden onset gastro-intestinal illness in humans. Their ability to cause large scale outbreaks of debilitating illness, even if of quickly passing nature, has made them into a relevant topic of study. Rapid developments in molecular biology have generated diagnostic tools which enabled many labs in the world to perform norovirus diagnostics, and to perform sequence analyses of the detected strains. These sequence data form a very valuable basis for studies of the molecular epidemiology of noroviruses. By linking the sequence data to classical epidemiological data, such as time and place of illness, number of people affected, etc., a platform is made for unveiling information describing for example the spread of the virus, the impact, and the prevalence. The work presented in this thesis aims to further current knowledge of norovirus by studying its molecular epidemiology, to better enable taking public health actions aimed at decreasing the impact of disease

Gastroenteritis Caused by Norovirus GGII.4, the Netherlands, 1994–2005

From 1994 through 2005, gastroenteritis outbreaks caused by norovirus generally increased in the Netherlands, with 3 epidemic seasons associated with new GGII.4 strains. Increased percentages of GGII.4 strains during these epidemics, followed by a sharp decrease in their absolute and relative numbers, suggest development of immunity

An Integrated Approach to Identifying International Foodborne Norovirus Outbreaks1

Surveillance gaps can be bridged through analysis of combined molecular and epidemiologic data

Emergence of New Norovirus Variants on Spring Cruise Ships and Prediction of Winter Epidemics

A reporting system could provide early warning

Phylodynamic Reconstruction Reveals Norovirus GII.4 Epidemic Expansions and their Molecular Determinants

Noroviruses are the most common cause of viral gastroenteritis. An increase in the number of globally reported norovirus outbreaks was seen the past decade, especially for outbreaks caused by successive genogroup II genotype 4 (GII.4) variants. Whether this observed increase was due to an upswing in the number of infections, or to a surveillance artifact caused by heightened awareness and concomitant improved reporting, remained unclear. Therefore, we set out to study the population structure and changes thereof of GII.4 strains detected through systematic outbreak surveillance since the early 1990s. We collected 1383 partial polymerase and 194 full capsid GII.4 sequences. A Bayesian MCMC coalescent analysis revealed an increase in the number of GII.4 infections during the last decade. The GII.4 strains included in our analyses evolved at a rate of 4.3–9.0×10−3 mutations per site per year, and share a most recent common ancestor in the early 1980s. Determinants of adaptation in the capsid protein were studied using different maximum likelihood approaches to identify sites subject to diversifying or directional selection and sites that co-evolved. While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication. We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant. While norovirus infections are generally mild and self-limiting, more severe outcomes of infection frequently occur in elderly and immunocompromized people, and no treatment is available. The observed pattern of continually emerging novel variants of GII.4, causing elevated numbers of infections, is therefore a cause for concern