I've been thinking about this for a while but with B.1.637.1 being assigned I've decided to write a thread about 'second generation variants'.
- What are they?
- Why should we be bothered about them?
- How should we look for them? github.com/cov-lineages/p…
Disclaimer – B.1.637.1 is almost definitely nothing to be worried about – its an interesting lineage that has some convergent evolution with Delta – seqs might increase in the coming weeks but this is mostly due to it being an S-gene target failure virus (false positive for BA.1)
So what are 2nd gen variants? I’m defining them as variant lineages (ie long branch lengths, no intermediates) that are derived from previous variant lineages. B.1.637.1 is the first clear example of one of these that been assigned by @PangoNetwork
B.1.637.1 is particularly interesting example as it shows some clear convergent evolution towards Delta, gaining T478R and P681R and several other mutations (when it already has L452R), though worth saying its parental lineage (B.1.637) wasn't all that interesting/successful.
Why should we care about 2nd gen variants? Well they are evolving from already existing, successful variants which already have nasty properties (antigenicity, transmissibility). This might mean its easier for them to get the right (or wrong for us) combo of mutations.
To use an analogy of climbing a 'fitness mountain' each current VOC has had to climb from the bottom. A second generation variant can start halfway up and capitalise on the gains of its parent lineage.
(apologies to @influenzal for the strained metaphor)
In all honesty I thought after Delta that a 2nd gen variant (maybe on an Alpha, Gamma, Mu or Delta background) was the most likely next 'variant lineage'... After some evidence appearing in the last few days I'm not entirely certain I was wrong....
Its become apparent in the last few weeks both Omicron and B.1.640 – two variant lineages with very long branch lengths, have minor ‘outgroups’ that are clearly related but very distant, with no apparent intermediates between them.
I propose one potential explanation for this is that both lineages are actually 'Second generation variants' where the original parental variant lineage has never been sampled for some reason or other. This may become clearer as more genomic/functional evidence is discovered.
Finally its worth mentioning it may be quite easy to miss 2nd gen variants as they will get called as the parental lineage they and share most of their parental lineage mutations. Its worth keeping an eye out for known variants with many more mutations than normal though.
Thanks to the @GISAID community and contributors for sharing their data allowing this kind of analysis to be done, to @PangoNetwork and its contributors for all their help and to @influenzal, @shay_fleishon, @nzm8qs, and @MoritzGerstung for some useful convos around this area!
It's been getting on for a year since I wrote this thread - heres a bit of an update of where we are with the evidence for mammal-to-mammal transmission of H5N1s.
What I'm not really able to cover yet is the North American cattle situation - not enough sequencing or epidemiological data has been shared to draw any strong conclusions - see this recent piece by @HelenBranswell This is frustrating to say the least...
Thinking about pandemic preparedness, H5N1 has (rightfully I think?) recieved a lot of attention over the last couple of years.
However I think there is another group of flu viruses that most folks working on flu might say pose a higher pandemic risk - swine influenza viruses.
Swine influenza viruses have recieved a bit of attention recently - with 'cryptic' (ie no know contact with pigs) infections found in the UK and the Netherlands in the last few months gov.uk/government/new…
Swine influenza viruses with pandemic potential more or less come in two flavours - those with haemagglutinin (HA) and other genes from historic human seasonal influenza viruses - often from 'reverse zoonotic' (human to pig) events from the 1970-1990s
There have been some interesting developments with the panzootic (aka a pandemic of animals) H5N1 in mammals over the last few months.
Though I'd write a brief thread covering Polish cats, South American sealions and European fur farms.
Firstly, a quick situational update on the panzootic in birds. We're now 3 years into this outbreak and the virus is continuing to spread across the world, largely impacting waterfowl and seabirds (including many that are endangered)
Beyond birds though, we're seeing more and more infections in wild mammals that we've ever seen before. This is particularly widespread in scavengers and predators (for example foxes in Europe)
Excited to see our paper on coronavirus discovery in UK bats out. Its a cool story with some great multidisciplinary work between conservationists, molecular biologists, bioinformaticians, virologists, structural biologists, and more.
First off we did find some sarbecoviruses (distantly related to sars1 and 2) that had detecatable human ace2 binding, however this was pretty weak. We also know that it doesnt take that much go switch from weak to strong binding with sarbecos though.
We also found that these viruses apparently cant use the ACE2 from the species they were isolated from. This isnt unheard of with sarbecos (particular clade 2) but is a little surprising I think?
Inspired by some recent discussion we wrote a short report for virological about how one of SARS-CoV-2's accessory proteins (called ORF8) appears to have gone missing over the last year (with @LongDesertTrain and @siamosolocani)
Good question... if you ask 10 different virologists they may give you 20 different answers... in animal models it doesnt seem that important, and variants such as Alpha were missing most of it (but still did fine)...
With our new paper just out thought I'd write a brief thread about one of the ways avian influenza virus ('bird flu') adapts to mammals (with a focus on the polymerase).
The natural host of influenza viruses is wild aquatic birds - ducks, geese, gulls, etc.
Flu is very good at jumping into other species, including mammals like pigs, dogs, horses, and of course humans.
Avian influenza cannot generally infect and replicate within mammals very efficiently. Because flu is an RNA virus and mutates very fast, it can quickly pick up adaptations. Sometimes these adaptations are enough to even transmit between mammals.