New Delhi: The bird flu virus could morph into an avatar that’s even more easily transmitted among humans, and there are live examples of such viruses in nature that aren’t too far away from acquiring such transmissibility, say a series of studies published in peer-reviewed journal Science.
The studies, published nearly eight months after being ready for publication, triggered international controversy as it involved scientists actually creating in their labs viruses that had acquired the ability to jump from human to human. Critics were concerned that publicizing details of such experiments could potentially be used by bioterrorists. The editors of Science finally decided to publish the papers after permission and consensus among peer scientists as well as funders of the project—the US and the European Union—that the way to devise defences against such viruses was to have as many experts around the world access such information as easily as possible.
“Our main conclusion is that the H5N1 bird flu virus can acquire the ability of aerosol transmission between mammals, and we show that as little as five mutations, but certainly less than 10, are sufficient to make H5N1 virus airborne,” said Dr Ron Fouchier, professor of molecular virology in the department of virology at the Erasmus Medical Center in the Netherlands.
The findings underscore the risk that a similarly transmissible virus might evolve naturally and cause a human pandemic, though the concerned scientists say their studies indicate that currently available drugs and vaccines are effective against the avian (A/H5N1) bird flu virus in ferrets and this may be the case for humans, too, though further research will be necessary.
Using an earthquake calamity as an analogy, Derek Smith, professor of infectious disease informatics at the University of Cambridge in the UK, said the current situation was equivalent to scientists discovering an active fault line. “What we have discovered in this working collaboration is that it’s an active fault line. It really could—it really could do something. And now what we need to know is, how likely is that?” he said in a tele press conference organized by Science.
In early January, India declared itself “bird flu free” after three consecutive months of no reports of avian flu cases though these appear every few years. India doesn’t have an official count of bird flu-related fatalities, but the World Health Organization counts 586 cases of people infected by bird flu in the last 25 years worldwide, and of those 346 have died, for a fatality rate of around 60%.
To determine what it would take for the A/H5N1 virus to become capable of airborne transmission via tiny droplets or “aerosols”, the scientists began by genetically modifying the virus. They changed three amino acids, the building block of proteins, that would be expected to increase the virus’ affinity for mammalian hosts.
They infected ferrets—which show symptoms of flu similar to humans—by applying the modified virus directly inside the animals’ noses. Then the researchers swabbed the noses of those ferrets and inoculated more ferrets, to see how the virus evolves. As the experiment proceeded, the researchers took tissue samples from the ferrets and sequenced the viruses they found. They consistently identified the mutations that had been added at the beginning. In addition, several other novel mutations appeared during the transmission experiments, which seemed to give the viruses an advantage for replicating in the nose and throat, and potentially for being transmitted by air.
Next, the researchers tested whether the “selected” mutant viruses could be spread to uninfected ferrets through the air, i.e. by respiratory droplets. They placed pairs of cages containing healthy and infected ferrets next to each other but not in direct contact. Most of the healthy ferrets became infected with the influenza virus. The animals later recovered, and in fact the mutant viruses were only found to be fatal to ferrets during pathology experiments when the virus was inoculated directly into the throat at extremely high doses. The researchers sequenced the airborne, infectious viruses and found five mutations that together conferred the ability for airborne transmission.
These mutations have all been detected individually, or in partial combination, in viruses found in nature. It has long been thought that to trigger a pandemic, influenza viruses must first mix their genomes with another virus in an animal host. In a related set of experiments, also published on Friday, however, such reassortment wasn’t necessary for the mutant virus to change its transmissibility characteristics.
Independent scientists, however, said there was no way to determine when such viruses could acquire the mutations necessary to become dangerous to humans. “It is important work, but I don’t they shed new, practical knowledge,” said Viren Sircar, a virologist at the University of Delhi. “Even if some viruses are two mutations away from morphing, nothing tells you when can those mutations occur. Days? Decades?”