Influenza A viruses, being negative-sense single-stranded segmented RNA viruses, are prolific but notoriously sloppy replicators. They make millions of copies of themselves while they infect a host, but in the process, often make small transcription errors. Most of these `errors' do little to help the virus, and many are detrimental to its survival.
Those that accidentally favor replication in the host, however, tend to carry on to produce more progeny, and if `fit enough', can drown out the earlier `wild type’ virus in the host.This process is called host adaptation, and while it can (and does) happen in the wild, it can be easily simulated in the laboratory as well via a classic serial passage study (see graphic above).
You basically inoculate a host with a `wild type’ strain of a virus, let it replicate a while, then take the virus from the first host and inoculate a second, and then repeat the process five, ten, fifteen times or more.
Over time, the virus tends to adapt to the new host (assuming there are no species barriers to prevent it), often increasing replication, virulence, and transmissibility.
Avian influenza viruses normally infect the gastrointestinal tract of birds, and must adapt to infect the respiratory tract in order to succeed in a mammalian host. Even then, the virus may be of such low virulence, that it produces little or no ill effects.
Six months ago, in Sci Rpts: H5N8 - Rapid Acquisition of Virulence Markers After Serial Passage In Mice, we looked at an experiment that found it only took 5 serial passages to turn normally benign (in mammals) HPAI H5N8 into a more virulent mammalian adapted virus.
Like H5N8, LPAI H5N2 infects poultry and wild birds, but hasn't been shown to cause illness in humans. There is some limited serological evidence that LPAI H5N2 can infect humans (see Avian Flu Antibody Survey In Poultry Workers – Taiwan 2012), but it appears to do so inefficiently, and without causing harm.Today we've a similar study to that H5N8 serial passage study, only this time researchers used a 2009 Korean strain of LPAI H5N2. Quite remarkably, it only took a single passage of the virus to change it from benign to 100% lethal (in mice, at least).
If this study sounds vaguely famliar, you may recall:
- In 2016, in Virology J : Adaptation Of HPAI H5N2 In Mice we saw similar results in a study using an HPAI H5N2 virus from China. In that case, however, it took 10 passages.
- Before that, in 2014's Serial Passage Of H5N2 In Mice, another study was done with an HPAI H5N2 virus collected in 2010, and they found increased virulence and replication efficiency after just 15 serial passages.
Jeong-Hyun NamSang-Mu ShimEun-Jung SongErica EspañoDae-Gwin JeongDaesub SongEmail authorJeong-Ki KimEmail author
First Online: 29 June 2017
Cite this article as: Nam, JH., Shim, SM., Song, EJ. et al. Arch Virol (2017). doi:10.1007/s00705-017-3451-9
Influenza A viruses must undergo adaptation to acquire virulence in new host species. In mouse models, host adaptation for virulence is generally performed through 5 to 20 lung-to-lung passages. However, highly pathogenic avian influenza viruses (e.g., H5N1 and H7N7 subtypes) have been observed to acquire virulence in mice after only a few in vivo passages.(Continue . . . )
In this study, a low-pathogenic avian influenza H5N2 virus, A/Aquatic Bird/Korea/CN2/2009, which was a prevalent subtype in South Korea in 2009, was serially passaged in mice to evaluate its potential to become highly pathogenic.
Unexpectedly, the virus became highly pathogenic in mice after a single lung-to-lung passage, resulting in 100% lethality with a mean death time (MDT) of 6.1 days postinfection (DPI).
Moreover, the pathogenicity gradually increased after subsequent in vivo passages with an MDT of 5.2 and 4.2 DPI after the second and third passage, respectively. Our molecular analysis revealed that two amino acid changes in the polymerase complex (a glutamate-to-lysine substitution at position 627 of PB2 and a threonine-to-isoleucine substitution at position 97 of PA) were associated with the increased pathogenicity; the PB2 E627K mutation was responsible for the initial virulence conversion (0 to 100% lethality), while the PA T97I mutation acted as an accessory for the increased virulence.
Jeong-Hyun Nam and Sang-Mu Shim contributed equally to this work.
Granted, this abstract only addresses increased pathogenicity - and does not mention transmissibility - so right now it may only be truly bad news if you happen to be a mouse living near an infected poultry farm.
But influenza viruses continually evolve, and the changes needed to turn LPAI H5N2 into a more easily transmittable virus in mammals could come from a different source or event.Over the years we've looked at the potential role of peridomestic animals (cats, dogs, rodents, small mammals, etc.) in spreading avian flu viruses, and affecting its evolution.
- In 2015, in Taking HPAI To The Bank (Vole) we looked at the susceptibility of the European bank vole to both H5 and H7 avian viruses, and concerns they may be getting past farm bio-security measures.
- Also in 2015, we looked at the expanded host range that is susceptible to infection with H5N6 in H5N6 Rising: Infecting Birds, Humans, & Even Cats.
- A little over a year ago, in Report: Skunks and Rabbits Can Catch And Shed Avian Flu, we looked at a report that suggested that infected small mammals were a plausible intermediate host, and may be part of the chain of transmission of avian flu.
- And last December, we saw hundreds of cats (and 1 veterinarian) infected with avian H7N2 in and around New York City (see J. Virology: Virulence Of A Novel H7N2 Virus Isolated From Cats In NYC - Dec 2016).