"Know thy enemy" -- many would consider that one of the most crucial rules of engagement in any war.
Now those waging war against the deadly H5N1 bird flu virus have come one step closer to knowing their enemy, or at least understanding how this crafty bug makes the leap from birds to humans.
In a letter published in the current issue of Nature, lead researcher Yoshihiro Kawaoka and his colleagues have identified two key changes that took place in some versions of the viral strain that allowed the virus to infect not only chickens and ducks but humans as well.
Kawaoka, a professor of virology at both the University of Wisconsin-Madison and the University of Tokyo, noted in the letter that the findings could help those tracking the virus determine the likelihood that a given strain could spread from birds to humans and from one person to another.
"The findings described by Kawaoka and associates address an important issue related to the process by which an avian or bird influenza virus could acquire the ability to infect humans," says Dr. Steven Hinrichs, director of the Nebraska Public Health Lab and director of the University of Nebraska Center for Biosecurity.
"It is a useful research tool," adds Dr. Gregory A. Poland, chief of the Mayo Vaccine Research Group and associate chair for research at the Mayo Clinic department of medicine in Rochester, Minn. "We can now begin to look at all of the known H5N1 strains and see whether these changes have occurred. If so, we can raise the red flag."
With regard to raising this flag, Hinrichs says that for a bird influenza virus to reach the level of a pandemic and become dangerous to humans, three things must occur. First, the bird virus must be virulent or capable of causing disease. Second, it must be a new virus that can avoid our existing immune system. And third, the virus must be able to spread from human to human.
"At the present time, the current H5N1 virus has only the first two characteristics," he says. "Dr. Kawaoka's research findings add to our ability to detect the basic element of the third characteristic, the ability to pass infection from human to human.
"Therefore, bird influenza viruses could be screened to determine whether this mutation has occurred, providing an early warning that the final or third capability now exists."
Mutations and Bird Flu Spread
As far as viruses like H5N1 are concerned, a mutation refers to any change that gives the virus a different ability -- like the ability to infect a dog, a cat or a pig, for example, or the ability to spread among humans.
"As long as new human cases occur, there is a potential each time that the virus will change in a way that increases it efficiency in terms of growth in human cells and, hence, its transmissibility," says Dr. Frederick Hayden of the Global Influenza Program of the World Health Organization (WHO) and professor of pathology at the University of Virginia in Charlottesville.
These changes can happen on their own, or they can arise through melding and combining with other viruses. The problem is that viruses mutate so quickly; the virus dealt with today may not be the one dealt with tomorrow.
Poland says that as H5N1 continues to change and diversify, it poses a moving target for researchers who sprint to keep pace with this flu bug's evolution.
"In some of the viruses they have isolated in humans, these viruses could attach to either avian or human receptors," he says. "The implication of this is that it's as if the virus is slowly adapting and learning how to expand its host range. This is very bad news indeed for humans."
Close to a Pandemic?
Aside from the implications of the research as an early warning tool, some experts say it offers a glimpse at how close we are to a pandemic.
"By analogy, the current H5N1 virus is like an enemy that possesses a nuclear device, has the intention of using the nuclear device, but does not have a delivery missile," Hinrichs says. "When all three are present, the enemy becomes fully capable, and we must increase our readiness to respond."
So far, not a single case of human-to-human transmission of H5N1 has been recorded. Also, the United States remains apparently untouched by H5N1, as no human or bird cases have yet been reported in the country.
"This shouldn't change the current pandemic threat situation, so there is no cause for added anxiety," Hayden says. If anything, he adds, the research taking place now could give agencies like WHO the upper hand in containing a potential pandemic before it has the chance to spread.
"It should be emphasized that this research does not indicate that the current H5NI bird virus has acquired these mutations," Hinrichs says. "The research adds to our knowledge by identifying the location of where changes in the virus could occur that would allow it to pass from human to human."
And in the fight to stem a pandemic, knowledge is a crucial weapon.
"These findings have an indirect implication for development of viral vaccines in that the target sites for the vaccine may incorporate the sites of the new mutations," Hinrichs says.
This means that those working to develop vaccines to fight H5N1 could use the newly discovered mutations to their advantage, exploiting the differences that set the human-infecting viruses apart from the crowd.
But Poland says research cannot keep pace with the accelerating changes in H5N1 and other potentially pandemic strains.
"Take 'if' out of your vocabulary. We absolutely, positively -- I will stake my life on it -- have a pandemic," Poland says. "No one knows when, how severe it will be, or what virus it will be. But what we can say is that the leading candidate right now is the H5N1 virus."