Some strains of Rotavirus find their way into the cells of the gastrointestinal tract by recognizing antigens associated with the type A blood group.

Histo-blood group antigens are known to promote binding of Norovirus and Helicobacter pylori cells to intestinal cells, but this had never been demonstrated in Rotavirus, a major intestinal pathogen that is the leading cause of severe dehydration and diarrhea in infants around the world.

Scientists at Baylor College of Medicine (Houston, TX, USA) examined the structure of a key part of a strain of the virus known as P[14] which provides a clue to how the virus infects human cells. The scientists used various techniques including protein expression and purification, crystallization, glycan array screening, inhibition and infectivity assays, and hemagglutination assays.

In strains of Rotavirus that infect animals, the top of a spike on the virus attaches to the cell via a glycan, one of many sugars linked together to form complex branched-chain structures with a terminal molecule of sialic acid. The same did not appear to be true of virus strains that infect humans, and scientists believed the human Rotavirus strains were bound to glycans with an internal sialic acid molecule, but they did not know how this occurs.

The investigators determined the structure of the top of the virus spike domain, known as VP8*, and found that the type A glycan bound to the Rotavirus spike protein at the same place as the sialic acid would have in an animal Rotavirus. They used crystallography, to show subtle changes in the structure of the VP8* domain of the virus that allowed it to use the histo-blood group antigen A as a receptor. An antibody to the histo-blood group antigen A blocked infection by the virus into human intestinal cells in culture. The authors found humans infected with the P[14] strain had type A blood, but more studies are needed to confirm the connection.

B. V. Venkataram Prasad, PhD, the lead author and professor of biochemistry and molecular biology at Baylor College of Medicine, said, "We wondered how this genotype of Rotavirus recognized a cellular glycan. We did a glycan array analysis to see which glycans interacted with the top of the virus spike, called VP8*. No one expected this. Is there an emerging theme here with these intestinal pathogens? Do other viruses use these blood group antigens as a door to enter the cell? The question now is do different strains use other histo-blood group antigens in this way?" Further studies identified a second Rotavirus strain P[9] that uses the histo-blood group antigen as a receptor. The study was published online on April 15 2012 in the journal Nature.

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