Researchers Find Mutation in Influenza A H5N1 Which May Increase Infectivity in Humans

I've discussed before a little about Influenza A H5N1 which is more commonly referred to in the media as "avian influenza". I may have to post some other time about what this nomenclature means, and how H5N1 comes about into a human population from the original avian source (or, even better, I might be able to directly link to a review article I recently wrote if it will be made available publicly by the publisher). So, I am sorry, but the following couple paragraphs will assume some background knowledge of influenza genetics and epidemiology:

However, suffice it to say that when H5N1 is referred to by the press as being seen in a human case; this is referring to a human case of disease where the human directly contracted this virus from an avian source. The classical case involves people who are in direct contact with poultry such as is seen in parts of Asia. This is important to point out because more evidence is pointing to this direct spread of H1N1 to humans prior to the 1918 pandemic.

This is surprising because until H5N1 became noticed in 2003 (and the more recent work on a recovered strain of 1918 H1N1); it had been conventional thinking that the appearance of entirely new strains of influenza occurred through other means. Specifically, this "Antigenic Shift" was thought to occur from the mixing of strains in animals such as pigs who are able to be infected by both avian and humanized strains of influenza A. This thinking mostly is based upon the study of the H2N2 and H3N2 pandemics which were less devastating than the H1N1 pandemic and are more likely to have been started by a partially humanized, yet new, virus. However, the implications of a fully avian pandemic are strikingly different.

One key point that is missing in the investigation of why and how do these avain viruses jump straight to humans lies in the specific interactions between the virus and it's host. This is fairly basic stuff; viruses are made up of DNA (or RNA in the case of influenza) just like humans are, and any changes to this genetic code has a direct impact on the structure and function of the virus. This is particularly explicit with viruses because they are such simple organisms that their genetic code is so much more analagous to a computer program. In a virus, a single base mutation can make the difference between infectivity in an entirely new host species or significant attenuation of virulence. In addition, because of the extremely rapid growth rates of many viruses, it is almost certain that in a population of virus, there exists (on average) at least one mutation per base position across the entire genome.

In the article cited below, the researchers discover a single change in amino acid to a Lysine at position 627 of the PB2 gene which confers a phenotype much more amenable to infection in a mouse model of human infection. Of course, the implications of this are significant in the study of how this gene, and it's related pathophysiology, is important to infection in humans. And, I have no doubt that there may exist other positions across the influenza genome which may also serve as 'switches' to turn on a more human-specific virus.

However, as I love to point out, this also serves as a target for genetic engineering of a pandemic strain of influenza which could be designed for dispersal into the human population. This reminds me of the report of mutations mousepox related to IL-2 regulation from Australia which profusely increased lethality (mousepox is related to smallpox, btw). So, thus is the consequencs of studying infectious agents for good cause, we need to be aware that this same information could be used for nefarious means.

• Hatta M, Hatta Y, Kim JH, Watanabe S, Shinya K, et al. Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice. PLoS Pathogens Vol. 3, No. 10, e133 doi:10.1371/journal.ppat.0030133