# 4039
It isn’t a new idea that the H5N1 virus needed to become better adapted to humans before it could be efficiently transmitted from one person to the next.
Scientists have argued for years, however, over what genetic changes would be required to make that happen.
Today we get a press release from Imperial College London regarding a PLoS One article published today on the subject. This is a rather lengthy press release, so I’ll only post the opening paragraphs.
Follow the link to read it in its entirety. The link to the study, and its abstract follow.
New research helps explain why bird flu has not caused a pandemic
Bird flu viruses would have to make at least two simultaneous genetic mutations before they could be transmitted readily from human to human, according to research published today in PLoS ONE.
The authors of the new study, from Imperial College London, the University of Reading and the University of North Carolina, USA, argue that it is very unlikely that two genetic mutations would occur at the same time. Today's new study adds to our understanding of why avian influenza has not yet caused a pandemic. Earlier this year, the Imperial researchers also showed that avian influenza viruses do not thrive in humans because, at 32 degrees Celsius, the temperature inside a person's nose is too low.
H5 strains of influenza are widespread in bird populations around the world. The viruses occasionally infect humans and the H5N1 strain has infected more than 400 people since 2003.
H5N1 has a high mortality rate in humans, at around 60 per cent, but to date there has been no sustained human to human transmission of the virus, which would need to happen in order for a pandemic to occur.
Today's study suggests that one reason why H5N1 has not yet caused a pandemic is that two genetic mutations would need to happen to the virus at the same time in order to enable it to infect the right cells and become transmissible. At present, H5 viruses can only infect one of the two main types of cell in the mouth and nose, a type of cell known as a ciliated cell. In order for H5 to transmit from human to human, it would need to be able to infect the other, non-ciliated type of cell as well.
The PLoS One link and abstract (reformatted for readability).
Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium
Citation: Ayora-Talavera G, Shelton H, Scull MA, Ren J, Jones IM, et al. (2009) Mutations in H5N1 Influenza Virus Hemagglutinin that Confer Binding to Human Tracheal Airway Epithelium. PLoS ONE 4(11): e7836. doi:10.1371/journal.pone.0007836
Abstract
The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease.
The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy.
To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread.
While parental H5 HA exhibited limited binding to human tracheal epithelium, introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly, these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates. Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an evolutionary “dead end.”
We conclude that, although genetic changes that adapt H5 to human airways can be demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that current H5 viruses will originate a human pandemic.
