22.06.2012

Russell et al., (2012) Science 336:1541-1547

Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, a group of researchers found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. The researchers used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host.
According to the model, factors that increased the likelihood of the virus evolving included random mutations and positive selection.  Viruses can replicate billions of times within a single host, sometimes imperfectly, leading to random mutations.  Positive selection may favor some of these mutations if they help the virus adapt to mammals and spread.
A long period of infection can also increase the likelihood of the virus evolving, because the longer a person is infected, the more the virus replicates and mutations can accumulate.  According to the researchers, it is also likely that there are other mutations not identified by the Foucheir and Kawaoka papers, which can act as functional substitutes for the three remaining mutations.
Finally, the diversity of the virus within the bird population can spell trouble for humans as well.  The more mutations there are within the bird population, the higher probability there is that a key mutation may be missed by routine surveillance. 
However, even after identifying those factors, as well as a few factors that may actually decrease the likelihood of avian influenza evolving, the researchers said it was impossible to determine the exact risk.
These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat.