The norovirus, a highly contagious source of food poisoning, has been successfully grown in the lab for the first time, report US researchers.
A constant threat to the food chain, in the US alone foodborne illness annually costs the country €5.79 billion. By bringing a greater understanding of the virus, this latest development in the laboratory may lead to improved tools to control the outbreaks.
"By looking at the mouse virus we have grown in the lab, we were able to identify a part of the capsid, the virus' protein shell, that is essential to its ability to cause disease," said senior author Skip Virgin, professor of pathology, immunology and molecular microbiology at the Washington University school of medicine in the US.
The US Centers for Disease Control and Prevention estimates that 23 million cases of acute gastroenteritis are due to norovirus infection, and it is now thought that at least 50 per cent of all foodborne outbreaks of gastroenteritis can be attributed to noroviruses. Most foodborne outbreaks of norovirus illness are likely to arise though direct contamination of food by a food handler immediately before its consumption.
Outbreaks have frequently been associated with the consumption of cold foods, including various salads, sandwiches, and bakery products. Liquid items - salad dressing or cake icing - that allow virus to mix evenly are often implicated as a cause of outbreaks.
Food can also be contaminated at its source, and oysters from contaminated waters have been linked to widespread outbreaks of gastroenteritis. Other foods, including raspberries and salads, have been contaminated before widespread distribution and subsequently caused extensive outbreaks.
Although such infections rarely lead to serious or life-threatening illness in Western countries, they spread rapidly, are difficult to prevent from spreading and can create considerable discomfort. In the developing world, these viruses are a major cause of human illness.
All previous attempts to culture human noroviruses in tissues in the laboratory have been unsuccessful.
"As a group, noroviruses have defied characterisation for decades because there just has not been a way to get the virus to grow outside of a human host," said Virgin.
In 2003, Christianne Wobus and Stephanie Karst, two postdoctoral fellows in Virgin's lab, identified MNV-1, the first known mouse norovirus. Virgin's group showed that the mice's ability to fight MNV-1 relied heavily on the innate immune system, the branch of the immune system that attacks invaders soon after they enter the body.
In the new paper, Virgin's group reveals that MNV-1 likes to infect cells of the innate immune system. In tests in mice, the researchers found the virus thrived in macrophages, immune system cells that normally engulf and destroy pathogens, and in dendritic cells, sentry-like cells that pick up and display proteins from pathogens.
To grow the virus in the lab, researchers took dendritic cells and macrophages from mice with defective innate immune systems and exposed them to the virus.
"The virus grew beautifully," commented Virgin.
While comparisons of MNV-1 and human noroviruses have revealed many similarities in gene sequence, structure and overall arrangement of the genome, Virgin acknowledges that differences between mouse and human physiology may significantly alter MNV-1's interactions with its host. For example, mice do not appear to be able to vomit.
Additionally, researchers are not sure yet whether MNV-1 can make mice with normal immune systems sick.
"The bottom line is that this mouse model provides us with a very useful way to examine certain similar aspects of the noroviruses," added Virgin.
Full findings of the study are published today in the 30 November issue of Public Library of Science Biology.