First Detailed Report of New Virus's Promiscuous Past

May 22, 2009

The most detailed description yet of the origins of the novel H1N1 virus causing the swine flu outbreak appears today on ScienceExpress. The study, conducted by an international team of scientists working at breakneck speed, has good news about the prospects of making a vaccine against the virus and raises the intriguing possibility that a species other than pigs might have harbored a precursor to it.

The study analyzed 76 isolates of the new virus taken from people in Mexico and the United States. It involved a team of 59 researchers led by investigators from the U.S. Centers for Disease Control and Prevention (CDC) and the University of Cambridge in the United Kingdom. At a CDC press conference today, the team's lead scientific spokesperson during the swine flu outbreak, Anne Schuchat, called the study a “big breakthrough from global scientific collaboration.” (Schuchat, CDC’s interim deputy director for science and public health program, is not one of the co-authors.)

Much of the data in the study has come out previously, some in earlier papers about the parents of the virus that “reassorted” to make this new H1N1, some in the flood of genetic sequences put into public databases, and some in press interviews with public health agencies and academic investigators. “CDC has done a great job of getting information out as soon as it is available, and some of this paper is the peer review of that information,” acknowledged one of the lead authors, evolutionary biologist Derek Smith of the University of Cambridge in the U.K. But he points out that many of the finer details have not appeared before.

Virologist Robert Webster of St. Jude Children’s Research Hospital in Memphis, Tennessee, one of the world’s leading influenza investigators, said the paper is “very, very useful” because it pulls together a lot of information that has dribbled out in many venues. “There’s nothing I didn’t know, but I’ve been in this business forever and ever,” said Webster. “And the people at CDC deserve to have this published. They bust their butts and have done the lion’s share of the work and tried to be as open as possible.”

All influenza viruses ultimately come from birds, and the paper begins the somewhat operatic and knotty story of this outbreak’s origins with an H1N1 first isolated in swine in 1930, which itself was a close relative of the virus that caused the 1918 pandemic in humans. Unlike flu viruses that affect humans, the eight influenza genes in this H1N1 changed very little for 6 decades. CDC chief influenza investigator and co-author Nancy Cox attributes that stability to the short life span of pigs, which means that their immune systems have much less opportunity to “pressure” flu viruses into changing. But in 1998, researchers discovered that this rock-steady swine H1N1 had combined with a human H3N2 and an American avian virus. This so-called triple reassortant spread to Asian pigs, and many different variants soon began popping up in swine all over the world.

In a separate drama, the H1N1 in humans that caused the 1918 pandemic was replaced by an H2N1 in 1957 but then suddenly reappeared in humans in 1977—many suspect a Soviet lab accident—and has been making the Homo sapiens rounds since.

Now along comes the swine flu outbreak of April. The paper explains that this novel H1N1 has two genes from an avian virus that entered Eurasian swine in 1979, three from the old-fashioned H1N1 in North American swine, two genes from the triple reassortants in North American swine, and the final one from humans transmitted to us from birds in 1968. That head-spinning mix has never been seen before, and given its genetic distance between known strains, CDC’s Cox said the virus was likely lurking around somewhere long before it jumped into humans—and it may not have been in pigs. “We do not know if the virus entered the human population directly from swine or via an intermediate host,” said Cox. Researchers are “now looking very carefully to see if they have in their freezers samples from pigs or other animals that might provide a missing link and information about intermediate viruses that could help narrow down the time and place of emergence of this novel influenza virus,” said Cox.

The study also has encouraging news for vaccine development. The many isolates of the new viruses analyzed in this report showed little variation among them. “We see much less variation among these new H1N1 viruses than we do for typical seasonal influenza viruses,” Cox said. This makes it “much, much easier” to make a vaccine that might work against the many different variations of the virus in circulation, she said.

—Jon Cohen