New Omicron preprint from us about replication in primary cells, receptor usage and entry routes (can be found here while screening on biorxiv): drive.google.com/file/d/1vam2PV…
Here are a couple of highlights
We looked at replication of Omicron in different cell types including primary human nasal epithelial cells (hNECs) – it consistantly replicates really really fast in these cells – even faster than Delta (which itself replicates faster than anything before!)
We could see the same doing competition assays (using variant specific RT-qPCR probes). No matter which isolates we used we could see Omicron replicates incredibly fast in primary nasal cells.
We confirmed Omicron likes to use human ACE2 then looked at which other species ACE2s it can use well - as others have found mouse ACE2 is very compatibly but so is horseshoe bat as well as some of the avian ACE2s which other variants haven't ever shown any usage of.
As others have described Omicron Spike is just not very fusogenic, this is in contrast to all previous SARS-CoV-2 variants...
...and is puzzling as in our hands N679K and P681H alone both enhance S1/S2 cleavage. It appears something quite strange is going on here with Omicron - maybe some sort of epistatic interaction somewhere else in Spike?
We describe evidence that Omicron Spike is more able to use the endosomal entry route than previous variants, being less sensitive to TMPRSS2-mediated entry and more sensitive to inhibitors of endosomal entry.
In live virus in primary cells, although TMPRSS2 inhibitors slow down Omicron, it eventually caught back up while Delta is completely inhibited. Despite being able to enter via the endosome Omicron live virus also appears completely resistant to endosomal IFITM inhibition.
Therefore we propose a model where Omicron has become less specialised in its entry route and become more of a 'generalist' - this allows it to efficiently infect a greater number of cells in the upper respiratory tract and may mean it even has a lower infectious dose?
Encouragingly, this work is very consistant with virological data on Omicron from our colleagues at @CVRinfo, @GuptaR_lab, @SystemsVirology, HKU, and more!
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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.