Seminar

Endemic and epidemic viral gastroenteritis: Mechanism of virus evolution and persistence in the human population.

Miren Iturriza, PhD

Gastroenteritis remains one of the major causes of morbidity and mortality worldwide, and viruses have been recognised in recent years as major contributors to the burden of infectious intestinal disease. Among viruses, rotavirus and noroviruses are globally distributed, with rotaviruses being associated with endemic disease and high morbidity and mortality in infants. Noroviruses are typically associated with milder disease and less attributable mortality, but with high burden of both endemic and epidemic disease. At present, effective vaccines for the prevention of rotavirus disease exist, and rotavirus vaccination programs are successfully reducing the burden of rotavirus disease in those countries that have implemented them. In contrast norovirus vaccines are not yet available, although recent trials with norovirus virus like particles (VLPs) show promising results. Advances in understanding the biology and mechanisms of disease and prevention as well as in the production of effective vaccines have been hindered by the lack of an in vitro system for norovirus replication, and of suitable animal models. Molecular epidemiology studies have revealed the great extent of norovirus diversity circulating in the human population, however, the distribution of virus genotypes differs according to age group and setting (eg, sporadic cases vs outbreaks), and to date it has not been possible to correlate genetic diversity with phenotypic diversity. These differences are likely to be the result of several factors, unlike rotaviruses in which animal reservoirs play an important role in the emergence of new strains, there appears not to be an animal reservoir for noroviruses. Therefore, diversity and persistence in the human population will be determined by virus and host factors including pre-existing immunity, herd immunity and virus-host interaction that are likely to be influenced by host genetic determinants. Human blood group antigens are known to bind to noroviruses, and regions within the virus capsid responsible for this interaction have been mapped. Though sequence analysis and in silico modeling, norovirus-specific strain putative epitopes have been determined and tested through the use of VLPs and specific monoclonal antibodies. However, detailed mapping of epitopes recognised by strain-specific antibodies, as well as identification of the molecules responsible for virus entry remain to be identified and characterized.