02/20/2012 03:13 EST | Updated 04/21/2012 05:12 EDT

Swine Flu Virus: Ferret Study Suggests New Virus May Have Pandemic Potential

TORONTO - A new study says flu viruses of swine origin that caused a dozen infections in the United States in the second half of last year appear to have pandemic potential.

And the work, by scientists at the U.S. Centers for Disease Control, seems to suggest that the fact the viruses haven't taken off in people may have more to do with human immunity than the viruses themselves.

The findings are based on a transmission study in ferrets, work which is somewhat similar to the studies that sparked the ongoing controversy over lab-made H5N1 viruses.

For several months now, Dutch and American researchers have been attempting to publish scientific papers showing how they developed H5N1 — bird flu — viruses that transmitted easily among ferrets, considered the best animal for predicting how a flu virus might behave in people.

At a World Health Organization meeting last week, a group of experts — many of whom were drawn from the world of influenza research — agreed that the studies should be published in full, despite a U.S. government request that key portions of data be kept out of the public domain.

The new study, published Monday in the journal Proceedings of the National Academy of Sciences, involves work with an H3N2 swine virus — now called an H3N2 variant — that has caused sporadic human cases in the United States, including some limited person-to-person spread.

The controversy over the H5N1 work relates to the fact that the research teams pushed the dangerous viruses to evolve to the point where they spread readily among ferrets, which might make the lab-made viruses transmissible among people. Currently H5N1 viruses rarely infect people, although when they do the infections are often fatal.

In the H3N2 variant study, the researchers didn't need to force the viruses to mutate so that they were able to infect ferrets. The viruses already seem well-adapted to infecting mammals, senior author Terrence Tumpey said in an interview.

The study looked at H3N2 variant viruses from 2009, 2010 and 2011. Over those years, the viruses changed. In particular, in 2011 the virus picked up a gene — the M gene — from the H1N1 virus that caused the 2009 pandemic.

The M gene, when tested in guinea pigs, seems to make flu virus more transmissible. That led flu scientists to hypothesize that the M gene might make it easier for the swine viruses to infect people and might explain what appeared to be an increase in human cases last year.

This study actually questions that finding, noting that H3N2 variant viruses from 2010 were as transmissible in ferrets as the 2011 version. "It is unclear whether the acquisition of the M gene ... enhanced the ability of A(H3N2)v virus to spread in pigs and infect people," the study said.

Tumpey, a microbiologist, said these viruses — which are distant cousins to human H3N2 viruses — attach to the same cell receptors that human flu viruses attach to. Avian influenza viruses attach to different receptors which aren't common in the human respiratory tract, which is thought to be why H5N1 viruses don't infect humans more frequently.

"Overall, for the more recent ones, the 2010 and 2011 viruses, we are seeing very efficient transmission events, similar to what we see with seasonal H3N2 viruses," Tumpey said of the H3N2 variant viruses.

"These viruses have the pandemic potential, but we also need more data to really understand the cross-reactive immunity in the general population to the H3N2 (variant) viruses."

After causing 12 cases from the end of July through the late fall, there hasn't been a human infection with the H3N2 variant spotted since before Christmas. Tumpey said some experts felt the cases would drop off after the season for agricultural fairs ended. A number of the cases involved exposure of people to sick pigs at these types of events.

He also noted that just as flu has a season in people, infections in pigs may peak at different points of the year, during which time the risk of transmission to people might be higher.

Another possible explanation for why the viruses haven't spread more broadly may relate to how much immunity humans have to them, Tumpey said.

The H3N2 viruses moved from humans into the pig population in the early 1990s; since then the human and pig versions have evolved along separate paths. It's thought that anyone born after the early 1990s would not have antibodies that would recognize and protect against those viruses. But people born before then may.

Finding out more about the immunity levels of humans to these viruses is important, the study said, to assessing how big a risk they pose.

A recent small study from Canadian researchers suggested there may be more vulnerability to these viruses in the human population than one might suspect. The work, published in the journal Eurosurveillance, saw no antibodies in children and teens, but strong levels in young adults. But by age 40, antibody levels start to tail off sharply, the study suggested.