Virologist Virgina Hinshaw studies flu virus in little piggies.
© 1994, University of Wisconsin-Madison Office of News and Public Affairs. Photo by Jeff Miller.
To evade the immune system, flu virus "drifts" from one form to another. But it's also got a faster, more threatening way to change its stripes: "antigenic shift."
Remember those viral surface protein, "H" and "N"? It turns out that "H" comes in 15 varieties, and "N" in nine. So like diners in a Chinese restaurant, flu could, theoretically, choose one from column "H" and one from column "N". (But just as chow mein does not go with chop suey, not every H and N combination might work.)
Today's human flus are mainly H1N1 and H3N2.
Even more drastic is a process called "reassortment," the mixing of genes from different flu strains. Reassortment can cause a shift in surface proteins, producing new strains with new H and N numbers.
This all must seem totally irrelevant, but there's a kicker: After a shift or a reassortment, the human immune system will have no antibodies to the new strain, and therefore no power to fight it.
Reassortment is rare, but it can translate into a pandemic -- a global outbreak of flu. That's what probably happened in 1918 (we'd know for sure if good viral samples were available). And that's what caused the Hong Kong flu (H3N2) pandemic of 1968.
Flu has another trick -- "jumping" the species barrier without reassortment. The Hong Kong boy who died this year was infected by an avian flu with H5 characteristics, apparently the first fatal transmission to a human of a totally "birdlike" virus. (The boy may have been infected at his preschool, which had on-premises chickens.)
H5 has a bad reputation. In the 1980s, after an outbreak of H5 flu, millions of chickens died (or were killed to prevent a spread of infection), says virologist Virginia Hinshaw. Although not all H5s are that deadly, "if a virus with that potential in birds got loose in people, you'd have a huge problem. That's why everybody gets a bit antsy [nervous] about H5."
Pork cocktail, anyone?
Where are flu genes blended into the new concoction we call antigenic shift? In what scientists call the "pig mixer." No, pigs don't operate test tubes or wet bars. But they can get three kinds of flu: swine, bird (avian) and human. (Achoo! No wonder they look so miserable...)
Let's say a human and a bird flu infect the same cell in a pig. It's unlikely, but possible. Each virus, doing its thing, 
would direct the cell to make more of its genes. Normally, the genes would then be reassembled into a new set of viral genes.
But pity the lowly viruses -- they get confused when two viruses are cranking out new genes inside the same cell, and the resulting virus particles can contain a mixture of genes from the different viruses. In fact, two viruses infecting the same cell can produce 256 different viruses.
Reassortment happens. The deadly 1957 Asian flu, for example, contained five human and three bird genes.
Because the genes determine the surface proteins, these proteins (antigens) will be different, and the human immune system will not recognize the new hybrid. The blended virus may not be able to infect humans, but if it can, it could carry new virulence, courtesy of its non-human genes.
At worst, antigenic shift can lead to a flu virus that can infect not just the respiratory tract, but also other parts of the body -- with serious consequences. That happens with many bird versions of the flu, says Hinshaw, and may explain the 1918 epidemic.
Sniffling, griping, laid up in bed? Is it a cold or a flu?
