Australia’s unseasonal flu season is still with us, albeit a little quieter than it was. Some
A harbinger of some H3N2 mismatch
Just this week a new preprint dropped. A preprint is a scientific paper that has not yet been peer-reviewed, but is open for everyone to read. It provided data suggesting Australia may have a difference between circulating and vaccine viruses. Some of the A/H3N2 viruses dominating Down Under in 2019 (members of a subgroup or “subclade” called 3c2.A A1b/131K) differ from the vaccine component virus chosen to protect us from them (a subclade A2/re virus, A/Switzerland/8060/2017).
We identified a potential antigenic mismatch of the H3N2 component of the 2019 Southern Hemisphere influenza vaccine. Nonetheless, it is important to continue to get vaccinated.@MackayIM@edwardcholmes@WHOCCFluMelb @sjturn
https://t.co/6N8vKlchrW— Hensley Lab (@SCOTTeHENSLEY) June 25, 2019
My great thanks to fluru (flu guru?) Scott Hensley, University of Pensylvania, for pinging me about his article on Twitter. And for doing this important work!
No sign of recombination yet
What else do we know? I downloaded 23 Australian complete genomes found on the GISAID EpiFlu sequence database. These sequences come from flu viruses detected
This sample of genomes is less than 0.02% of all the flu cases recorded between November 2018 and June 25th. This means it’s not representative of anything specifically; there are too few and we don’t know why they were selected. But it’s interesting. It does give us a glimpse that there is lots of A/H3N2 viral diversity around. And this seems to be a growing feature of our flu seasons.
The main reason I created this tree was to compare it to trees made using the other 7 segments. I’m not showing all of that working here – just two examples below. I’ve compared the HA gene segments to the neuraminidase (NA) gene segments or to the nonstructural (NS) gene segments.
See more explanation about influenza genetic segments and genomes at An influenza virus is the sum of its parts
I can tell you that the same pattern resulted from all 7 comparisons. The same subclades within HA appeared in the trees made using the other 7 genes.
Not a tangled forest
There was no sign in these “tangle trees” that one of the H3N2 viruses had swapped a gene segment with another FluA virus. If they had it would have shown up as a line from the left (HA) side matching up to a different coloured partner on the right. This process, called recombination, could result in a child virus with different properties from either parent. Perhaps one that could survive or transmit more efficiently during summer, for example.
Australia’s unseasonal flu season has a couple of main drivers in my opinion. One hypothesis is that a distinct virus arising from genetic recombination kicked off the early flu season; co-infecting viruses sharing their gene segments. It wasn’t surprising that this little experiment didn’t find any evidence to support that. We’ll need more sequences to be able to really test that.
Another hypothesis is that there have been mutations within one or more of the gene segments. This or these perhaps bestowed upon the mutants improved virus stability or transmission. The mutants might last longer on surfaces for us to pick up or be hardier in droplets, floating longer for us to inhale. Finding evidence of that will also take more full genome sequences. It’ll also need analysis and knowledge of the impact of changes to the viral proteins resulting from genetic mutations.
Both hypotheses will need us to look more deeply at influenza than we have to date and to do that more regularly. And we should communicate what we find, as we find it instead of waiting for the high impact factor journal.
We need more viral genomics
We should consider working whole genome sequencing into flu surveillance with as much gusto as we cling to our beliefs that everything we need to know about seasonal influenza can be found in 12.5% of its genes.
There’s still lots of work to do in the field of seasonal influenza. Australia’s unseasonal flu season is just the latest reminder that we often settle for not knowing rather than seeking out precise answers.