Serial passage of H5N1 can create an airborne virus

H5N1 is an extremely lethal flu virus. However, to become a pandemic virus, it must be transmitted efficiently between humans. Although there have been numerous clusters of human to human spread of H5N1, it has not yet succeeded in sustained transmission. Why not?

Viruses can be transmitted by direct contact on surfaces or in the air. There have been a few documented H5N1 clusters where airborne spread seems a likely explanation, but these did not result in further spread, perhaps due to specific environmental conditions associated with those outbreaks. Because efficient airborne spread of H5N1 among humans has not yet occurred, some suggest that the virus is incapable of acquiring this ability. This has now been proven to be a false assumption.

From Scientific American, September 19, 2011 [hat-tip, Goju]


…researchers wonder: Could the dreaded H5N1 ever morph into a disease that could spread among people, via a cough or sneeze, to attach to nasal or tracheal membranes, as the seasonal flu does every year?

To help answer this question, Ron Fouchier, also of Erasmus Medical Center, and his team “mutated the hell out of H5N1” and looked at how readily it would bind with cells in the respiratory tract. What they found is that with as few as five single mutations it gained the ability to latch onto cells in the nasal and tracheal passageways, which, Fouchier added as understated emphasis, “seemed to be very bad news.”

The variety that they had created, however, when tested in ferrets (the best animal model for influenza research) still did not transmit very easily just through close contact. It wasn’t until “someone finally convinced me to do something really, really stupid,” Fouchier said, that they observed the deadly H5N1 become a viable aerosol virus. In the derided experiment, they let the virus itself evolve to gain that killer capacity. To do that, they put the mutated virus in the nose of one ferret; after that ferret got sick, they put infected material from the first ferret into the nose of a second. After repeating this 10 times, H5N1 became as easily transmissible as the seasonal flu.

The lesson from these admittedly high-risk experiments is that “the H5N1 virus can become airborne,” Fouchier concluded—and that “re-assortment with mammalian viruses is not needed” for it to evolve to spread through the air. And each of these mutations has already been observed in animals. “The mutations are out there, but they have not gotten together yet,” Osterhaus said.


Serial passage has long been known to be an effective way to increase the transmissibility of viruses in a new host. By inoculating one animal, collecting the viruses that survive, and inoculating another animal, investigators are selecting for the viral variants that are best adapted to the new host. In the experiments described above, it took 10 “rounds” of passaging from animal to animal to achieve an H5N1 virus which could spread efficiently in the air.

One of the reasons why human clusters of H5N1 are so dangerous is because each human to human transmission increases the probability that H5N1 will become completely adapted to humans and spread efficiently in the air. In effect, each human to human transmission is one passage of the virus. It now seems clear that concern about pandemic H5N1 is justified. There is now no reason to assume that H5N1 cannot become airborne in humans.

Although the scientists doing this work were interested in modeling natural evolution, it should be noted that they likely created a very dangerous virus in the laboratory. We don’t know how lethal a virus adapted to ferrets would be to humans, but given that we are both mammals and that ferrets accurately model many aspects of human influenza infection, there is a good chance that the virus created is quite dangerous to humans. One interesting aspect of this experiment is that this was achieved with a relatively low tech approach: serial passaging of virus in a new host. Such an approach could be imitated by bad actors with only modest technical skills and equipment.

Are we prepared for a highly lethal, highly contagious virus, whatever its origins? No, we are not, imo.


2 thoughts on “Serial passage of H5N1 can create an airborne virus

  1. we had been waiting for that really,really stupid in 2006.
    Now 5 years are passed and it didn’t increase spread in/to humans,
    so people became less and less concerned.
    Will they model how that virus may spread in humans ?
    Becoming less virulent should help the virus

  2. gsgs, no, becoming less virulent won’t necessarily help the virus. Consider HIV. Its been spreading human to human for over 30 years and is still nearly 100% lethal without treatment.

    As long as the host is alive when he is infectious, it doesn’t matter what the virus ultimately does to him.

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