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The human norovirus (also known as the winter vomiting bug) is a major cause of gastroenteritis worldwide and is responsible for the deaths of many children in developing countries. Norovirus infections are estimated to have an economic cost of over 60 billion US dollars per year, yet there are no vaccines or drugs to prevent or limit the spread of outbreaks. In most cases norovirus infections last only a few days but, in people with weakened immune systems, infections can last from months to years.
A norovirus particle consists of a molecule of ribonucleic acid (or RNA for short), which contains the genome of the virus, surrounded by a coat of proteins. The virus is unable to multiply on its own and so it infects the cells of its host and hijacks them to make new viral proteins and RNA. Host cells have their own RNA molecules, which provide the instructions that cellular machines called ribosomes need to make proteins. Recent work reported that a norovirus protein called VPg interacts with the host cells’ ribosomes to recruit them to produce proteins from the viral genome. However, it remained unclear which host proteins were important for this key stage of the norovirus life cycle.
Hosmillo, Lu, McAllaster et al. combined three different molecular biology and genetic approaches to search for host proteins that help noroviruses to multiply in cells. Any proteins identified in these experiments would be fundamental for the norovirus life cycle, making them potential drug targets for future treatments. The experiments revealed that a protein called G3BP1 was required for noroviruses to multiply efficiently. Previous studies have shown that G3BP1 is a member of a family of proteins that can bind to RNA and play many roles in healthy cells, including helping the cells to adjust the proteins they produce in response to stress. Hosmillo, Lu, McAllister et al. found that G3BP1 helped VPg to recruit ribosomes and the other host components needed to make new proteins from the viral RNA genome.
These findings reveal a new role for G3BP1 in allowing noroviruses to multiply within cells and identifies a potential weakness in the norovirus life cycle. In the future, this work may help researchers to identify new drugs that could control norovirus outbreaks or treat long-term norovirus infections in humans.