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Avian flu adapts to human hosts
May, 2015

A woman holds a goose while two man wearing hazardous suits vaccinates the goose

With multiple columns in the daily paper devoted to Ebola's frightening rashes and bleeding, you'd be forgiven for forgetting that Ebola is far from the only emerging infectious disease that threatens human health today. Avian flu may be less dramatic and mainly infects birds, but it is no less deadly when it makes its way into a human host, with the worst strains killing 60% of people infected. We first wrote about the H5N1 avian flu back in 2005, but this is a bug that keeps coming back! Most recently, Egypt has experienced a surge of infections: 132 cases since January. All of them seem to have been passed to humans directly from infected birds. Now, new studies reveal that the Egyptian strain has evolved adaptations that allow it to more easily pass from bird to human, raising the possibility that the virus could soon evolve the ability to move from human to human — a development that would let this dangerous virus loose on humans all over the world, regardless of their proximity to infected poultry.

Where's the evolution?

When Evo in the News last reported on H5N1, we discussed horizontal transfer — i.e., the possibility of a human flu virus passing the gene versions necessary for human-to-human transmission to the avian flu. While horizontal transfer is still a threat, new research focuses on the incremental adaptations that the avian flu virus evolved as natural selection acted on it within human hosts. In particular, the new research focuses on avian flu strains from Egypt, which are unusually good at making the leap to mammals from birds. What evolutionary changes are responsible for this ability?

Illustration of the influenza virus infecting a protein host

Human flu viruses have adaptations that allow them to invade human cells in our upper respiratory system; however, bird flu works in a different way. It mainly invades cells in birds' intestines. Which cells a flu virus can bind to and attack is determined at least partly by a protein called hemagglutinin — HA for short — that is positioned on the outside of the virus. HA recognizes and binds to the victim cell, ultimately prompting the host cell to envelope the virus. HA also helps the virus release its genetic material (in this case RNA) once it is inside the host cell, allowing more copies of the virus to be produced.

The new study focused on HA proteins and catalogued the mutations that differentiated the Egyptian viruses that had invaded humans from other H5N1 viruses. The researchers then inserted copies of those mutations into more typical H5N1 viruses and investigated the effect those had on the virus and its HA proteins. They discovered that the mutated HA proteins made the viruses better able to bind to cells lining the human airway and also altered when the virus released its RNA inside the host cell. This allowed the mutant bird flu viruses to replicate more efficiently inside human cells — though not (yet!) as efficiently as human flu viruses do.

Natural selection seems to have acted on the Egyptian viruses' HA proteins, favoring genetic variants in humans that are copied more quickly. This is exactly how we would expect natural selection to occur in this situation. In Egypt, humans come into close contact with infected poultry, and so the viruses frequently wind up in the human airway. When they do, any virus particle carrying a mutation that allows it to invade and replicate in a human cell would be favored. As the infection continues in that host, any random mutations that happen to make that process even more efficient would be favored.

So what's stopping these Egyptian avian flu viruses from being passed from human to human? The viruses have some of the adaptations that would be necessary for this to occur, but not all of them. They can infect and replicate quickly inside human cells, but other research suggests that they'd have to be better at growing in the upper respiratory tract and stable enough to remain infectious when outside the host's body. And it appears that some of the mutations favored in the Egyptian strain, while increasing replication within the host, actually make the virus less stable and so potentially less able to move from human to human.

Nevertheless, the Egyptian viruses have high pandemic potential, since they are already unusually good at infecting humans. This research gives us a much clearer picture of what adaptations are involved when a virus switches hosts — and points the way towards some practical steps that can be taken to prevent a pandemic, such as close monitoring of viral strains that are primed for human infection.

Read more about it

Primary literature:

  • Watanabe, Y., Arai, Y., Daldoji, T., Kawashita, N., Ibrahim, M. S., El-Gendy, E. E. M., Hiramatsu, H. ... Ikuta, K. (2015). Characterization of H5N1 influenza virus variants with hemagglutinin mutations isolated from patients. mBio. 6: e00081-15.
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News articles:

Understanding Evolution resources:

Discussion and extension questions

  1. Why did the scientists interested in the Egyptian strain of avian flu choose to study the HA protein?
  2. How did the differences between the Egyptian H5N1 viruses and more typical H5N1 viruses arise?
  3. Review the process of horizontal transfer. How is this process similar to and different from the process of mutation that generated the Egyptian H5N1 viruses?
  4. Review the concept of random mutation. In your own words, explain in what sense the mutations that helped adapt H5N1 to human hosts are random.
  5. Review the process of natural selection. Use the four steps described on that page to explain how an avian flu lineage might evolve adaptations that enable it to better reproduce in human hosts.
  6. Advanced: What factors or situations might foster the evolution of avian flu viruses that can be passed from human to human? Explain your reasoning.

Related lessons and teaching resources

  • Teach about avian flu: This news brief for grades 9-16 describes the threat of avian flu and how horizontal transfer could result in the evolution of an even deadlier virus.
  • Teach about random mutation and natural selection: In this activity from Access Excellence for grades 9-12, students build, evolve, and modify paper-and-straw "birds" to simulate natural selection acting on random mutations.


  • McNeil Jr., D. G. (April 13, 2015). Egypt's avian flu surge lacks an explanation. Retrieved April 29, 2015 from The New York Times (http://www.nytimes.com/2015/04/14/health/egypts-avian-flu-surge-lacks-an-explanation.html).
  • Neumann, G., Macken, C. A., Karasin, A. I., Fouchier, R. A. M., and Kawaoka, Y. (2012). Egyptian H5N1 influenza viruses — cause for concern? PLoS Pathogens. 8: e1002932.
  • U. S. Department of Health and Human Services. H5N1 avian flu (H5N1 bird flu). Retrieved April 29, 2015 from Flu.gov (ww.flu.gov/about_the_flu/h5n1/).
  • Watanabe, Y., Arai, Y., Daldoji, T., Kawashita, N., Ibrahim, M. S., El-Gendy, E. E. M., Hiramatsu, H. ... Ikuta, K. (2015). Characterization of H5N1 influenza virus variants with hemagglutinin mutations isolated from patients. mBio. 6: e00081-15.

Photo courtesy of Reuters. Illustration of influenza A virus courtesy of NIH.gov.