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Tracing the Lineage of the New H1N1 Strain

H1N1 is simply one combination of two of these subtypes that give the virus an appearance recognizable to the immune system -- say, short black hair and a long nose. Within these subtypes, however, there are subtle -- and sometimes not so subtle -- variations. They arise from mutations in the genes governing the H and N proteins.

Over time, an H1N1 influenza A virus can change its appearance significantly through random mutation. It can streak its short black hair and put a gold stud in its long nose one year, and shave its hair into a Mohawk and add a diamond stud in the other nostril the next. Pile up enough of these, and pretty soon the immune system no longer recognizes it as the virus with the short black hair and the long nose it once knew -- even though it still fits that description.

That is why the Spanish flu virus, the new swine flu virus and some of the human flu viruses circulating in recent winters can all be H1N1 viruses and yet look and behave so differently.

Research in the past few years on the Spanish flu virus -- which has been reconstructed from fragments extracted from lung-tissue samples from people who died in 1918 -- has revealed that much but not all of its killing potential resided in the H protein. One of the reassuring things about the new swine flu strain is that it does not have those same "virulence factors," even though it shares the same broad H1N1 features.

Studies done in the past two weeks suggest that people who have received flu shots in the past few years -- shots that protect against the most common human H1N1 strain in circulation -- are not protected against this swine flu strain, even though it also is H1N1. Why? Because it looks so different to the immune system that the virus-killing antibodies do not react.

Such is the importance of looks, immunologically speaking.

The human H1N1 flu virus -- and it's "human" only because it is in us -- that circulates each winter changes a little bit year to year in a phenomenon called "antigenic drift" as mutations creep into the H and N genes. But it can also change much more rapidly through something called "antigenic shift," which happens when entire H or N proteins (or both) are swapped out wholesale for new versions.

This is possible because influenza's genes are on eight separate strands, or "gene segments." One or two or more can be replaced, like cards in draw poker.

That's a rare event, however, and requires that two flu strains invade a single cell, replicate and then get their products mixed up in the packaging. The result is a virus dramatically different in immunological appearance, and sometimes in disease-causing capability, from either parent.

One way or another, a new influenza virus with the identity of H2N2 appeared in 1957. Because it was a new combination, nobody had immunity. It was called "Asian flu," and it spread everywhere, outcompeting H1N1 strains, which disappeared in people but remained in pigs.

In 1968, another strain, an H3N2 combination, appeared on the scene. Nobody had immunity to it either. It had a world's worth of susceptible victims and caused the "Hong Kong flu" pandemic that year and the next.

In 1977, a strange thing happened. The H1N1 virus, absent for years in people, reappeared. Curiously, it was almost exactly like the last strains in the 1950s. It was so close, in fact, that many people suspect it was released into the world by mistake from 1950s samples kept in a lab freezer.

Whatever the source, it spread widely as the "Russian flu," infecting lots of people born after the disappearance of H1N1 two decades earlier.

Since then, H1N1 and H3N2 strains have been circulating, mutating in small ways, and infecting new victims year to year. At the moment, the dominant H1N1 strain is one called A/Brisbane/59/2007. By chance, the dominant H3N2 strain was also found in Brisbane, Australia, in 2007 and is named A/Brisbane/10/2007. Influenza B, which has caused about one-third of infections in the United States this flu season, is dominated by a strain called B/Florida/04/2006.

But now comes a whole new H1N1 virus. It is formally labeled A/California/04/2009 (see graphic), and it was taken from a 10-year-old boy in San Diego who came down with the flu on March 30. It has an H from an H1N2 virus circulating in American pigs and an N from an H1N1 virus found mostly in Eurasian ones.

Our immune systems, familiar with other H's and N's, do not know what to make of it. We have no antibodies against the combination, so we have no protection against it. And we will generate antibodies only if we get infected by the virus or vaccinated with a killed version of it; either way will teach the immune system what it looks like.

This is the swine flu or, as the federal government likes to call it, confusingly but inoffensively, the H1N1 strain.

It's coming soon to a neighborhood near you. But we don't yet know how this tale will end.

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