Recombinomics Commentary 07:00
April 4, 2013
Webby said the H7N9 viruses are showing changes that are hallmarks of adaptation to mammals, the same types of mutations that have been seen when other flu viruses — which all have their origins in water birds like ducks — learn to infect mammalian species.April 4, 2013
One of the changes is in what's know as the receptor binding site. Bird viruses use a different receptor to latch on and trigger infection than flu viruses that have adapted to infect humans and other mammals. And the genetic sequences of the H7N9 viruses show they have started to make that change, Webby said.
As well there are a couple of other mutations seen in these H7N9 sequences that are known to be indicators of viruses that have switched to mammalian hosts from avian hosts, he said.
The above comments describe the receptor binding domain change Q226L. Although multiple media reports are beginning to cite genetic changes, none actually say the name of the change (and some, like the ECDC risk assessment completely ignore it)
The change is well known and all three studies on H5N1 transmission introduced this change prior to ferret infections. Moreover the 1957 pandemic, which involved H2N2 had the change, as did the H3N2 in the 1968 pandemic. When new H5N1 bird flu cases were reported, agencies would claim that the H5N1 couldn’t transmit human to human (H2H) because the two key changes, Q226L and G228S, were not present. Neither of the changes have been reported previously in H5N1 or H7 isolates from any species.
Thus, the presence of Q226L in the two most recent sequences has caused considerable concern, although media reports, like the one cited above just discuss Q226L in general terms, in contrast to prior reports on H5N1 transmission studies, which commonly cited the two key changes by name.
However, the appearance of Q226L is very recent. The first isolate, A/Shanghai/1/2012 had PB2 E627K and the 5 amino acid deletion in the N9 stalk, but Q226L was not present. This isolate was from the first confirmed case (87M) who was part of a suspect cluster. Q226L was in the two subsequent isolates, A/Shanghai/2/2013 from the second confirmed case (27M) and A/Anhui/1/2013 from the third confirmed case (35F).
This recent development has been followed by an explosion of cases. There have been six additional confirmed cases ringing Shanghai (seemap). Like the first 3 cases, all have been severe (fatal or hospitalized in the ICU). There have also been two recent suspect deaths (see map) and more cases are being cited on twitter (see map).
The recent appearance of Q226L, as well as D225G on H7 and E627K on PB2 raises concerns that the number of severe and fatal cases will spike higher.
Release of sequences from the recent cases would be useful. The presence of Q226L in most recent cases is expected, and the appearance of additional receptor binding domain changes, such as G228S would be catastrophic.
