1918 and bird flu: Finding transmission tipping point’
Two bird viruses, but one spread among humans
Based on ongoing research with the resurrected 1918 H1N1 pandemic virus, it appears that avian influenza H5N1 bird flu could rapidly adapt and spread through the human population with a few genetic changes that allow a transmission "tipping point."
Comparing the 1918 flu virus with the currently circulating bird flu, researchers have found that avian H5N1 has acquired five of the 10 gene sequence changes associated with human-to-human transmission in the 1918 virus.
"We know that the handful of changes that are shared between the recent H5N1 viruses and the 1918 virus might be evidence that this process is beginning, but clearly those changes are not adequate by themselves to allow the H5N1 virus to be transmissible," says Jeffery K. Taubenberger, MD, PhD, the Armed Forces Institute of Pathology researcher who reconstructed the 1918 pandemic flu strain by scavenging viral fragments from three of its victims. Currently, H5N1 avian flu can infect humans from birds, but the virus is then mired within us.
"There must be kind of a tipping point," he says. "If one person is directly infected with a H5N1, the virus can go through a couple of rounds of replication. During those rounds of replication in the lungs it might be already selecting for a couple of changes that are beneficial in the new environment. But if that virus is no longer transmissible, it’s a dead end. It becomes extinct. That is what we are seeing [with bird flu]."
Indeed, looking at different viral cultures of human infections with H5N1 avian flu, one can see genetic changes here in one, there in another, he explains. "But they are not additive," Taubenberger emphasizes. "The only way for them to become additive is if the virus is able to go from person to person — even poorly. Transmissibility has got to be the tipping point. Once that happens the other changes that would tailor the virus to make it perfectly human adapted would probably happen pretty fast. Ultimately, the key is trying to understand what controls transmissibility. Unfortunately, nobody at this point has an explanation of what mutations have to occur in what genes for that to happen."
The completely assembled genome of the 1918 virus is avian-like in appearance, but it is not yet understood how it became so transmissible in humans. Unlike the 1957 and 1968 pandemic flu strains, the 1918 strain neither re-assorted with a human virus nor reformed genetically by infecting pigs — the classic "mixing vessel" for flu strains, he says.
"What makes the 1918 virus funny’ at a sequence level, is not the changes within the proteins, not the coding changes, but this larger number of silent changes throughout the genome that make it like quite different from the bird flu viruses that we currently know about," Taubenberger says.
In essence, the 1918 virus appears to have maintained an entirely avian appearance while mutating sufficiently to become a human flu strain. "That means, at least theoretically, that both of those options are available to [bird flu]," he says. "It could still re-assort with a current circulating human virus and create a pandemic a la 1957, or it might continue down the [avian] path that ultimately led to 1918. It increases concern, not only because of those shared changes, but now it seems there are two possibilities [for a pandemic to emerge]."
If the transmission factors in the 1918 virus can be identified, it may be possible to develop molecular based surveillance to detect "parallel evolution" in avian H5N1 or another possible pandemic flu strain. In other words, eliminate any virus that nears the aforementioned transmission tipping point.
"If you find a virus that is accumulating some of the changes that are crucial [to transmission] you would want to go in and completely eliminate that strain," he says. "If that is on one farm, you would really want to go in and cull that farm and treat everybody around with [the antiviral] Tamiflu. Eliminate that strain and triage [those exposed]. In that way we may be able to prevent pandemics from ever occurring again if we have good molecular-based surveillance. That is my long-term hope."
Based on ongoing research with the resurrected 1918 H1N1 pandemic virus, it appears that avian influenza H5N1 bird flu could rapidly adapt and spread through the human population with a few genetic changes that allow a transmission tipping point.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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