Many of the world's deadliest flu outbreaks--including those that killed over 100,000 Americans alone in 1957 and 1968--did the viral version of the triple jump, passing from birds to pigs to finally infecting people. Now researchers know why pigs are the baneful middlemen. A new study in the September Journal of Virology shows that pig cells have two kinds of receptors: one targeted by flu strains that infect birds, the other by flu strains that infect people. The study provides the first molecular evidence that pigs can serve as "mixing bowls" where avian and human flu strains swap genetic material to form new bugs to which humans have little defense.
Influenza viruses infect many animal species, but birds appear to be the largest reservoir for new flu varieties. Strains that infect birds, however, only rarely jump directly to people, as happened in Hong Kong last year. Flu strains owe this specificity to the particular type of bond between sugars on the receptors of cells they infect. Flu strains that infect human cells, for example, recognize receptors with so-called a2,6 linkages, while the ones that infect birds recognize a2,3 bonds.
University of Wisconsin, Madison, virologist Yoshihiro Kawaoka and his colleagues wondered what kind of sugar bonds are present in pig cell receptors. To find out, his group unleashed a pair of sugar-seeking missiles: two lectin molecules, one of which binds only to sugars in an a2,3 bond, the other to sugars in an a2,6 bond. They attached fluorescent labels to the lectins, squirted the hybrids one at a time to pig trachae cells, and then washed the cells to remove anything that didn't bind. The cells lit up in both cases, confirming that each lectin was binding to its preferred sugar. The researchers concluded that the pig cells have both receptors--those targeted by flu viruses that infect humans and those targeted by flu viruses that infect birds. This supports the widespread speculation that it's here, in pigs, where separate viuses swap genetic material and breed dangerous new strains.
"This is a very nice piece of work" that confirms the central role of pigs in the transmission of new flu strains, says Nancy Cox, who heads the influenza branch at the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia. She says the findings suggest that public health officials should consider launching systematic surveillance programs of flu strains infecting pigs, so they have a better idea what sort of new flu strains may emerge to strike people.