Old antibodies help some people ward off infection by the swine flu virus. Credit: Pasieka / Science Photo Library

As far as your immune system is concerned, the pandemic H1N1 (swine) flu virus currently circling the globe bears an uncanny resemblance to an influenza virus that wreaked havoc nearly a century ago, researchers have found.

For months, it has been apparent that swine flu strikes the young more often than the old — an unusual pattern that suggests older patients could have been exposed to similar viruses in the past. A new study released today by Nature suggests that people alive during the infamous 1918 influenza outbreak have the greatest protection against the current swine flu1.

The study also included experiments in a veritable menagerie of animals, including mice, miniature pigs, ferrets and macaques. In all but the pig, the virus yields an infection in the lungs that is more severe than would be expected from an average seasonal flu, according to Yoshihiro Kawaoka of the University of Wisconsin-Madison and his colleagues, who conducted the study.

Of mice and macaques

Kawaoka's team also confirmed that some commercially available antiviral drugs, including oseltamivir (marketed by Roche as Tamiflu) and zanamivir (marketed by GlaxoSmithKline as Relenza), are effective against the new pandemic virus in human cells grown in the lab. These drugs are already being used to treat some infected patients.

Meanwhile, Kawaoka's studies generally echo the findings of two Science papers released last week, which reported that swine flu reproduces more aggressively and produces more severe disease in ferrets than seasonal flu (see Swine flu reaches into the lungs and gut). Kawaoka's team observed this virulence in mice and macaques as well, but pigs showed no outward signs of disease even though the virus reproduced capably in the swine respiratory system. This, the authors suggest, could explain why farmers have not reported an outbreak of sick pigs.

The animal studies used higher doses of virus than humans would normally encounter — a practice that is common for such experiments. Nevertheless, one alarming feature of the macaque results was the development of severe pneumonia that extended throughout the lungs, notes Earl Brown, a virologist at the University of Ottawa. "Pneumonias are normally more localized," he says. "When you start to hit all areas of the lungs severely, that's when you can get a life-threatening situation."

The researchers also analyzed samples collected from humans, and found that those born before 1918 were more likely to produce antibodies capable of neutralizing the swine flu virus. That protection is somewhat counterintuitive: on the basis of DNA sequence alone, the two viruses are not strikingly similar. But it is still possible that the immune response elicited by one virus can offer protection against the other (see Old seasonal flu antibodies target swine flu virus).

Oddly, exposure to similar viruses that circulated from the 1920s to 1950s was not enough to elicit these antibodies — a result that doesn't mesh with the lower infection rates among those who are over the age of 60 but were not alive in 1918. One possible explanation is that antibodies that are not able to fully neutralize a virus can nevertheless offer some protection against infection, Brown says.

At present, most swine flu infections are mild, and the severity of the present pandemic does not come close to the 1918 flu, but experts worry that the new virus could become more virulent over time. Meanwhile, the virulence seen in the animal studies is disquieting, says Brown. "We're trying not to push the panic buttons, but we're trying to be realistic," he says. "There is some cause for concern here."