How Noroviruses cause repeated outbreaks of gastroenteritis
Posted by ajcann on April 9, 2008
Noroviruses are the leading cause of viral gastroenteritis (stomach flu), the symptoms of which include nausea, vomiting, and diarrhoea. There is no treatment for infection with these highly contagious viruses. While most people recover within a few days, the very young and old may experience severe disease. Like influenza, large outbreaks (epidemics) of Norovirus infection occur periodically (often in closed communities such as cruise ships), and most people have several Norovirus infections during their lifetime. Currently, many people are being infected each week in England with a new GII.4 variant. There are several reasons for this pattern of infection and reinfection. First, the immune response induced by a Norovirus infection is short-lived in some people, but not all. Second, there are many different noroviruses. Based on their genomes, noroviruses belong to five genogroups, which are further subdivided into genotypes. An immune response to one Norovirus provides little protection against noroviruses of other genogroups or genotypes. Third, like influenza viruses, noroviruses frequently acquire small changes in their genome. This process is called antigenic drift. Norovirus epidemics occur when virus variants emerge to which the human population has no immunity.
It is unknown exactly how noroviruses change over time or how they persist in human populations. In addition, little is known about susceptibility to Norovirus infections except that secretor-positive individuals people who express histoblood group antigens (HBGA) on the cells that line their mouths and guts are more susceptible than secretor-negative people, who express these antigens only on red blood cells. Information of this sort is needed to devise effective intervention strategies, therapies, and vaccines to reduce the illness and economic costs associated with norovirus outbreaks. In this study, the researchers investigate the molecular mechanisms governing the emergence and persistence of epidemic norovirus strains in human populations by analyzing how GII.4 Norovirus strains (the genotype usually associated with epidemics) have changed over time.
These findings suggest that the part of the Norovirus capsid protein that binds to sugars on host cells is under heavy immune selection and evolves over time by antigenic drift. They show that, like influenza viruses, GII.4 viruses evolve through serial changes in the capsid sequence that occur sporadically after periods of stability, probably to evade the build up of immunity within the human population. Variation in this region of the viral genome is possible because human populations express a great variety of HBGA molecules so there is always likely to be a subpopulation of people that is susceptible to the altered virus. Overall, these findings suggest that it should be possible to develop vaccines to protect against Norovirus infections but, just as with influenza virus, surveillance systems will have to monitor how the virus is changing and vaccines will need to be reformulated frequently to provide effective protection against Norovirus outbreaks.
Mechanisms of GII.4 Norovirus Persistence in Human Populations. PLoS Medicine 5, 2, e31
Our data suggest that the surface-exposed carbohydrate ligand binding domain in the Norovirus capsid is under heavy immune selection and likely evolves by antigenic drift in the face of human herd immunity. Variation in the capsid carbohydrate-binding domain is tolerated because of the large repertoire of similar, yet distinct HBGA carbohydrate receptors available on mucosal surfaces that could interface with the remodeled architecture of the capsid ligand-binding pocket. The continuing evolution of new replacement strains suggests that, as with influenza viruses, vaccines could be targeted that protect against Norovirus infections, and that continued epidemiologic surveillance and reformulations of Norovirus vaccines will be essential in the control of future outbreaks.
