Norovirus and gastrointestinal disease
Norovirus is currently recognized as the most important non-bacterial pathogen causing gastroenteritis. It is believed that majority of gastroenteritis that occur throughout the globe is attributed to Norovirus. Norovirus was first recognised through immunoelectron microscopy (IEM) in 1972. However, it is only over the past decade that Norovirus has been of great interest to the basic scientists, virologists, epidemiologists and public health experts. There is no doubt that outbreaks or epidemics of Norovirus in the coming years will challenge the medical community to the limit. Globalisation has created a single, very mobile mega-population of people on earth in which more viruses can thrive, and, a highly infectious illness caused by Norovirus can spread rapidly, thus creating epidemics or even pandemics. The potential breakthrough in the development of Norovirus vaccine with the development of effective antigenic viral-like particles (VLP), and the recognition that Norovirus evolves with antigenic drift will pose exciting challenges to all stakeholders. The other challenges or obstacles which we face include understanding the pathogenesis of the Norovirus in the gastrointestinal tract and identifying the site in the gastrointestinal tract which the virus replicates. This knowledge will hopefully allow the development of targeted antiviral therapy and thus prevent manifestation of severe clinical symptoms.
This is a review of this very exciting, virus and I have chosen to amalgamate the current literatures into the following topics:
Virology- Classification and structure
Biology- Replication and infectivity
Epidemiology- Geographic and temporal distribution
Prevention and control
Recent knowledge on contamination/sanitation and personal hygiene
Treatments- Current and future
Health impact of Norovirus outbreaks in the coming era
Although Norovirus was first viewed in 1972, it was not until 1990 when it was classified. Classification of Norovirus could finally be performed due to the successful cloning of the viral genome (1). Molecular cloning and characterisation of Norovirus genome allowed this virus to be classified as a member of Caliciviridae family and it is known as a Group B Biodefense Pathogen. Caliciviruses are small (27-40nm), non-enveloped, icosahedral particles with single-stranded RNA of positive polarity. The name calicivirus comes from the Latin word calyx, meaning “cup” or “goblet”, which describes the cup-shaped depression, as observed under electron microscopy. Although they share similar features to that of the picornaviruses, caliciviruses are distinguished from their counterpart by having a larger genome and having distinctive spikes on the surface. Another example of calicivirus is the Hepatitis E virus (2). Currently, there are a few serotypes of Norovirus which were successfully identified through immunoelectron microscopy (IEM) and enzyme-linked immunosorbent essay (ELISA), which are represented by Norwalk virus (NV), Hawaii virus (HV), Snow Mountain agent (SMA), Desert Shield virus (DSV) and Southampton virus. (1).
Currently, there are five main genogroups of Norovirus being identified (GI, GII, GIII, GIV and GV). Noroviruses, which can be found in humans, are from three genogroups (GI, GII and GIV). However, those that are commonly isolated in cases of acute gastroenteritis in humans belong only to two genogroups (GI and GII), which can then be further divided into genetic cluster or genotypes (i.e GI.1, GII.15, GIV.2 etc). There are now, at least 25 genotypes of Norovirus which were successfully identified, with the prototype Norwalk virus being labelled as GI.1 (Genogroup I, genotype 1) (3) and present within this genotype are numerous subtypes. The presence of this diversity of Norovirus strains are mainly due to both the accumulation of point mutations associated with error-prone RNA replication and to recombination between two related viruses (4, 5). Genogroup I (GI) includes76 Norwalk virus, Desert Shield virus and Southampton virus and Genogroup II (GII), includes Bristol virus, Lordsdale virus, Toronto virus, Mexico virus, Hawaii virus and Snow Mountain virus. Norwalk virus (NV), Snow Mountain virus (SMV), and Hawaii virus (HV) are the prototype strains of genotypes GI.1, GII.2, and GII.1 and are the causative agents of an estimated 5%, 8%, and 7% of Norovirus outbreaks, respectively (6). Genogroups III and V (GIII and GV) have only been identified in animals.
Through structural studies and visualisation of Norovirus by electron microscopy, it is now proven that the Norovirus is composed of 90 dimers of the major capsid protein VP1 and one or two copies of the minor structural protein VP2 (7) which recognizes the histo-blood group antigens, which are regarded as receptors and host-susceptibility factors for infection (3).