Norovirus

Norovirus, also known as Norwalk virus and sometimes referred to as the winter vomiting disease, is the most common cause of gastroenteritis. Infection is characterized by non-bloody diarrhea, vomiting, and stomach pain. Fever or headaches may also occur. Symptoms usually develop 24 hours after being exposed, and recovery typically occurs within one to three days. Complications are uncommon, but may include dehydration, especially in the young, the old, and those with other health problems.
The virus is usually spread by the fecal–oral route. This may be through contaminated food or water or person-to-person contact. It may also spread via contaminated surfaces or through air from the vomit of an infected person. Risk factors include unsanitary food preparation and sharing close quarters. Diagnosis is generally based on symptoms. Confirmatory testing is not usually available but may be performed by public health agencies during outbreaks.
Prevention involves proper hand washing and disinfection of contaminated surfaces. There is no vaccine or specific treatment for norovirus. Management involves supportive care such as drinking sufficient fluids or intravenous fluids. Oral rehydration solutions are the preferred fluids to drink, although other drinks without caffeine or alcohol can help. Hand sanitizers based on alcohols tend to be ineffective against noroviruses due to their being non-enveloped, although some virus genotypes are more susceptible.
Norovirus results in about 685 million cases of disease and 200,000 deaths globally a year. It is common both in the developed and developing world. Those under the age of five are most often affected, and in this group it results in about 50,000 deaths in the developing world. Norovirus infections occur more commonly during winter months. It often occurs in outbreaks, especially among those living in close quarters. In the United States, it is the cause of about half of all foodborne disease outbreaks. The virus is named after the city of Norwalk, Ohio, where an outbreak occurred in 1968.

Signs and symptoms

Norovirus infection is characterized by nausea, vomiting, watery diarrhea, abdominal pain, and in some cases, loss of taste. A person usually develops symptoms of gastroenteritis 24 hours after being exposed to norovirus. General lethargy, weakness, muscle aches, headaches, and low-grade fevers may occur. The disease is usually self-limiting, and severe illness is rare. Although having norovirus can be unpleasant, it is not usually dangerous, and most who contract it make a full recovery within two to three days.
Norovirus can establish a long-term infection in people who are immunocompromised, such as those with common variable immunodeficiency or with a suppressed immune system after organ transplantation. These infections can be with or without symptoms. In severe cases, persistent infections can lead to norovirus‐associated enteropathy, intestinal villous atrophy, and malabsorption.

Virology

Transmission

Noroviruses are transmitted directly from person to person and indirectly via contaminated water and food. Transmission can be aerosolized when those stricken with the illness vomit or by a toilet flush when vomit or diarrhea is present; infection can follow eating food or breathing air near an episode of vomiting, even if cleaned up. The viruses continue to be shed after symptoms have subsided, and shedding can still be detected many weeks after infection.
Vomiting, in particular, transmits infection effectively and appears to allow airborne transmission. In one incident, a person who vomited spread the infection across a restaurant, suggesting that many unexplained cases of food poisoning may have their source in vomit. In December 1998, 126 people were dining at six tables; one person vomited onto the floor. Staff quickly cleaned up, and people continued eating. Three days later others started falling ill; 52 people reported a range of symptoms, from fever and nausea to vomiting and diarrhea. The cause was not immediately identified. Researchers plotted the seating arrangement: more than 90% of the people at the same table as the sick person later reported becoming ill. There was a direct correlation between the risk of infection of people at other tables and how close they were to the sick person. More than 70% of the diners at an adjacent table fell ill; at a table on the other side of the restaurant, the infection rate was still 25%. The outbreak was attributed to a Norwalk-like virus. Other cases of transmission by vomit were later identified.
In one outbreak at an international scout jamboree in the Netherlands, each person with gastroenteritis infected an average of 14 people before increased hygiene measures were put in place. Even after these new measures were enacted, an ill person still infected an average of 2.1 other people. A US Centers for Disease Control and Prevention study of 11 outbreaks in New York State lists the suspected mode of transmission as person-to-person in seven outbreaks, foodborne in two, waterborne in one, and one unknown. The source of waterborne outbreaks may include water from municipal supplies, wells, recreational lakes, swimming pools, and ice machines.
Shellfish and salad ingredients are the foods most often implicated in norovirus outbreaks. Ingestion of shellfish that has not been sufficiently heatedunder poses a high risk for norovirus infection. Foods other than shellfish may be contaminated by infected food handlers. Many norovirus outbreaks have been traced to food that was handled by only one infected person.
From March and August 2017, in Quebec, Canada, there was an outbreak of norovirus that sickened more than 700 people. According to an investigation by Canada's CFIA Food Control Agency, the culprit was frozen raspberries imported from Harbin Gaotai Food Co Ltd, a Chinese supplier. Canadian authorities subsequently issued a recall on raspberry products from Harbin Gaotai.
According to the CDC, there was a surge in norovirus cases on thirteen cruise ships in 2023, which marks the highest number of outbreaks since 2012.

Classification

Noroviruses are a genetically diverse group of single-stranded positive-sense RNA, non-enveloped viruses belonging to the family Caliciviridae. According to the International Committee on Taxonomy of Viruses, the genus Norovirus has one species: Norwalk virus.
Noroviruses can genetically be classified into at least seven different genogroups, which can be further divided into other genetic clusters or genotypes.
Noroviruses commonly isolated in cases of acute gastroenteritis belong to two genogroups: genogroup I includes Norwalk virus, Desert Shield virus, and Southampton virus; and II, which includes Bristol virus, Lordsdale virus, Toronto virus, Mexico virus, Hawaii virus and Snow Mountain virus.
Most noroviruses that infect humans belong to genogroups GI and GII.
Noroviruses from genogroup II, genotype 4 account for the majority of adult outbreaks of gastroenteritis and often sweep across the globe.
Recent examples include US95/96-US strain, associated with global outbreaks in the mid- to late-1990s; Farmington Hills virus associated with outbreaks in Europe and the United States in 2002 and in 2004; and Hunter virus which was associated with outbreaks in Europe, Japan, and Australasia. In 2006, there was another large increase in NoV infection around the globe. Reports have shown a link between the expression of human histo-blood group antigens and the susceptibility to norovirus infection. Studies have suggested the capsid of noroviruses may have evolved from selective pressure of human HBGAs. HBGAs are not, however, the receptor or facilitator of norovirus infection. Co-factors such as bile salts may facilitate the infection, making it more intense when introduced during or after the initial infection of the host tissue. Bile salts are produced by the liver in response to eating fatty foods, and they help with the absorption of consumed lipids. It is not yet clear at what specific point in the Norovirus replication cycle bile salts facilitate infection: penetration, uncoating, or maintaining capsid stability.
The protein MDA-5 may be the primary immune sensor that detects the presence of noroviruses in the body. Some people have common variations of the MDA-5 gene that could make them more susceptible to norovirus infection.

Structure

Genus	Structure	Symmetry	Capsid	Genomic arrangement	Genomic segmentation
Norovirus	Icosahedral	T=1, T=3	Non-enveloped	Linear	Monopartite

Viruses in Norovirus are non-enveloped, with icosahedral geometries. Capsid diameters vary widely, from 23 to 40 nm in diameter. The larger capsids exhibit T=3 symmetry and are composed of 180 VP1 proteins. Small capsids show T=1 symmetry, and are composed of 60 VP1 proteins. The virus particles demonstrate an amorphous surface structure when visualized using electron microscopy.

Genome

Noroviruses contain a linear, non-segmented, positive-sense RNA genome of approximately 7.5 kilobases, encoding a large polyprotein which is cleaved into six smaller non-structural proteins by the viral 3C-like protease, a major structural protein of about 58~60 kDa and a minor capsid protein.
The most variable region of the viral capsid is the P2 domain, which contains antigen-presenting sites and carbohydrate-receptor binding regions.

Evolution

Groups 1, 2, 3, and 4 last shared a common ancestor in AD 867. The group 2 and group 4 viruses last shared a common ancestor in approximately AD 1443. Several estimates of the evolution rate have been made varying from 8.98 × 10⁻³ to 2.03 × 10⁻³ substitutions per site per year.
The estimated mutation rate in this virus is high even compared with other RNA viruses.
In addition, a recombination hotspot exists at the ORF1-ORF2 junction.