Until now, virology experts believed that human noroviruses, a leading cause of acute gastroenteritis, infect human cells by interacting with antigenic sugars that define human blood types. A research team now reports that they also bind to a different class of cell-surface carbohydrates found on gangliosides.
The work could aid development of antiviral agents or vaccines for human norovirus, which infects millions of people and kills more than 200,000 worldwide each year. No therapeutics or preventives are available to treat the infections.
The study was carried out by John S. Klassen and coworkers at the University of Alberta with Ming Tan and Xi Jiang at Cincinnati Children’s Hospital Medical Center (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja505272n). Mouse norovirus is known to bind to gangliosides and not to blood-group antigens. The new study shows the human version of norovirus binds to both.
Jacques Le Pendu of the University of Nantes, in France, whose group discovered human norovirus/blood-group-antigen binding, says scientists had already assumed that other ligands or receptors were at play. That’s because expression of blood-group antigens is not sufficient to allow infection in vitro, and some rare human norovirus strains do not appear to attach to the antigens. “Discovering that several gangliosides are ligands of at least two norovirus strains therefore constitutes a very important step in norovirus research,” he says.
Klassen and coworkers used electrospray ionization mass spectrometry to show that capsid proteins of two human-infecting norovirus strains bind to the oligosaccharides of gangliosides with affinities similar to that of human norovirus/blood-group-antigen binding. They are now trying to establish whether the finding applies to other human noroviruses, the diversity of which is large and keeps evolving.
Molecular virologist Stefan Taube of the University of Lübeck, in Germany, a member of the group that discovered that mouse norovirus binds gangliosides, says the new finding “is surprising and raises many important questions” about the mechanism of human norovirus cell entry. Klassen and coworkers plan to study whether infection requires that the virus bind both classes of carbohydrates in a particular order or if binding either one will do.
Le Pendu notes that human rotaviruses, the other major type of enteric virus, bind the same two classes of cell-surface carbohydrates. He says the new finding suggests that binding to both ligands “is required for an efficient human enteric infection and that the two types of viruses evolved similar mechanisms of attachment and possibly of cell entry. This opens up new lines of enquiry for both noroviruses and rotaviruses.”