Wild geese and rushes - Huang Chu Tsai
Wild Geese and Rushes
(Huang Chu Tsai – 
– Sung Dynasty)

Where did avian influenza come from?

The H5N1 avian influenza virus infects mainly birds, but there have been plenty of cases of spread into humans, where it is much more virulent than the ordinary, generic human influenza viruses that sweep around the world each year. H5N1 avian influenza is actually a group of related viruses, not just a single virus; and although it’s now mainly a virus of chickens and ducks, it was originally a pathogen of waterfowl.

When viruses jump from one species to another, they’re usually poorly adapted to their new host. Most often, the new host probably doesn’t even notice the infection. Sometimes the virus may be highly pathogenic, and may even rapidly kill the new host: Ebola virus (bat to human), Sin Nombre virus (rodent to human), and SARS virus (palm civet to human), are all examples of this. But in spite of high virulence, the virus isn’t necessarily well adapted to the new host; it doesn’t transmit effectively from one individual to another, and the infection burns itself out, only sustained by repeated jumps from the original population into the new one. That’s the phase we’re in with avian influenza.

SARS virus, though, is also an example of another viral phenomenon. The virus may be poorly adapted at first, but viruses (with their 24-hour generation time and in many cases their high mutation rates) evolve fast. What’s more, though the new host may not be a good fit in some ways, the entire population should be immunologically naïve — that is, there should be no immune resistance to the virus in the new host, in contrast to the original host, which typically would have a fair bit of resistance spread around the population. If the virus can adapt to the new host at all, there’s a smorgasbord of victims for it to infect. SARS virus jumped from palm civets into humans a few times, and then it rattled around in humans for a bit, gradually adapting and accommodating itself to humans instead of civets, until it was — well, not a very good human pathogen, but at least it was adequate at transmitting itself; it was capable of a sustained epidemic with further input from the parental civet virus.

Not much is known about how viruses acclimate to new species. Since it’s generally assumed that the next pandemic influenza outbreak of humans will come from the H5N1 virus once it’s become better adapted to humans, it’s of obvious interest to learn how it made its earlier jump to become adapted to chickens and ducks. A recent paper in PLoS Pathogens1 tracks the virus back to its roots.

Rooster (Historiae animalium lib. I.)Influenza viruses have a segmented genome — that is, the RNA that makes up the viral genome is split into eight separate pieces. If two influenza viruses infect the same cell, then when the new pieces of RNA get packaged up to make a virus, you can get reassortment — the progeny viruses can contain RNA segments from two different parental viruses. Did H5N1 adapt to domestic birds through reassortment with a well-adapted chicken virus, or did it make the jump all at once, as a single virus, and later on become better adapted?

Vijaykrishna et al looked at a lot of virus sequences and concluded that the virus did originally jump to ducks from migratory waterfowl as a single already-formed virus. The common ancestor of all the present H5N1 viruses probably formed, in migratory waterfowl, around 1994 — a couple of years before H5N1 was detected as a highly virulent pathogen of domestic ducks, which was in 1996.

After it was introduced into ducks, then new reassortants did arise — probably as the virus began to acclimate to its new hosts:

Analysis of virus population dynamics revealed a rapid increase in the genetic diversity of Gs/GD lineage in poultry in China from mid-1999 to early 2000. This corresponds with the period when each of the major Gs/GD-like H5N1 variants or sublineages diverged and subsequently became widespread in poultry throughout China. It is likely that combined strong ecological and evolutionary factors led to this rapid increase in diversity, namely, the spread of the virus through large, immunologically naive poultry populations…1

The authors suggest that China is a particularly good greenhouse for new H5N1 viruses to arise, probably because of the large and frequently connected population of domestic birds:

… transmission of these reassortant viruses within large highly connected populations of duck and other poultry species results in frequent interspecies transmission and genetic drift. Therefore, it is likely that this process selects for relatively fit viruses with a broad host range which are subsequently exported to other geographical regions. It is interesting to note that further reassortment has not been observed once those H5N1 viruses were transmitted out of China. We suggest that host population structures elsewhere may not result in the same intense multi-species transmission we observe in southern China.1

The selection for “relatively fit viruses with a broad host range” is the main concern here, I think. The next pandemic is likely to come out of China.

  1. Dhanasekaran Vijaykrishna, Justin Bahl, Steven Riley, Lian Duan, Jin Xia Zhang, Honglin Chen, J. S. Malik Peiris, Gavin J. D. Smith, Yi Guan, Ron A. M. Fouchier (2008). Evolutionary Dynamics and Emergence of Panzootic H5N1 Influenza Viruses PLoS Pathogens, 4 (9) DOI: 10.1371/journal.ppat.1000161[][][]