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Our paper on #ACE2 and #TMPRSS2 variation–the genes coding for the main receptors for #SARSCoV2 in our cells–in savanna monkeys (genus #Chlorocebus, or #vervets) is just out in @PLOSONE! Let me walk you through what we did and what this means… 1/24 https://doi.org/10.1371/journal.pone.0235106">https://doi.org/10.1371/j...
First off, this was a collaboration including tweeps @bergeycm @RutgersU, @ankajasinska @ucla, @HannesSvardal @AntwerpU, and other excellent colleagues not on Twitter from @wakehealth, local collaborators in South Africa @UFSUpdates, and Trudy Turner, mother of us all @UWM… 2/24
As #COVID19 spreads, it& #39;s affecting lots of communities – including those living with non-human primates (NHPs). Work by @AMelinLab @nyuprimatology @mariekecora suggests most African & Asian NHPs are vulnerable to #SARSCoV2… 3/24 https://leakeyfoundation.org/dozens-of-non-human-primates-are-vulnerable-to-covid-19/">https://leakeyfoundation.org/dozens-of...
This worried us, because not only are NHPs at risk for #anthroponosis (humans passing #SARSCoV2 to monkeys/apes, which could be devastating for their conservation), but there’s the complementary risk of #zoonosis, or sick NHPs passing it back to humans… 4/24
These are a concern with savanna monkeys because they interact with humans A LOT: in game/nature reserves, raiding crops on farms, in the pet trade, in wildlife sanctuaries, and, famously, (thanks @BBC) stealing alcoholic beverages at Caribbean resorts… 5/24
We also saw this as a concern because savanna monkeys have been shown to express human-like disease when infected with #SARSCoV. Moreso than #rhesus monkeys, which are the current NHP disease model being used for #SARSCoV2… 6/24 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111808/">https://www.ncbi.nlm.nih.gov/pmc/artic...
The #SARSCov and #SARSCov2 viruses both use the same two receptors to enter human cells: #ACE2 and #TMPRSS2. For a handy guide (with great illustrations) explaining how this works, follow this link… 7/24: #3933fbb32b27">https://www.forbes.com/sites/jvchamary/2020/04/17/coronavirus-spike-protein/ #3933fbb32b27">https://www.forbes.com/sites/jvc...
Given the two viruses use the same receptors to access cells, and the analysis of @AMelinLab, we wondered if #Chlorocebus could also get sick with #SARSCoV2. This might also make it a model for vaccine discovery & testing treatments in captive colonies like at @wakehealth… 8/24
Recent research, out after we wrote this paper, shows savanna monkeys can, indeed, be infected with #SARSCoV2, and when they are infected, they develop respiratory disease (mild, but more pronounced than in other NHP models)… 9/24 https://www.biorxiv.org/content/10.1101/2020.05.17.100289v1">https://www.biorxiv.org/content/1...
On top of that, infected savanna monkeys also shed infectious #SARSCoV2 in their mucus and feces for up to 21 days after their initial exposure to the virus. This establishes savanna monkeys as good models for vaccine and treatment development… 10/24 https://www.biorxiv.org/content/10.1101/2020.06.20.137687v1">https://www.biorxiv.org/content/1...
(If you live near savanna monkeys, before getting too worried, it’s important to know that #SARSCoV2 has NOT been documented in wild monkeys. We’re just assessing that potential.)… 11/24
Now, @AMelinLab found #ACE2 variation *between* primate species predicted to alter binding efficiency with #SARSCoV2. This was done for one individual of each species. But we wondered: is there #ACE2 or #TMPRSS2 variation *within* species that might moderate risk?... 12/24
So, we checked out functional variants in genomic data we’d already generated (with funding from @NIH @NSF and several other funders) on 245 savanna monkeys: 163 from the wild across Africa and the Caribbean, and 82 in an established captive colony at @wakehealth… 13/24
You can see these data for yourself, btw, using either our fancy new Vervet Genome Browser:
https://coppolalab.ucla.edu/vgb/home
Or">https://coppolalab.ucla.edu/vgb/home&... good ol’ Ensembl (like we did in this study):
https://useast.ensembl.org/Chlorocebus_sabaeus/Info/Index
14/24">https://useast.ensembl.org/Chloroceb...
https://coppolalab.ucla.edu/vgb/home
Or">https://coppolalab.ucla.edu/vgb/home&... good ol’ Ensembl (like we did in this study):
https://useast.ensembl.org/Chlorocebus_sabaeus/Info/Index
14/24">https://useast.ensembl.org/Chloroceb...
We found variation in both genes, but focused on variants coding for residues (amino acids) that might actually lead to changes in protein structure & function that might lead to poor #SARSCoV2 binding. In #TMPRSS2, we didn’t find any compelling variants. But in #ACE2… 15/24
Green monkeys (or Ch. sabaeus), the West African & Caribbean sub-species (or species, depends on who you ask), have a common variant at locus X:14077550 that changes the 30th amino acid in #ACE2 from aspartic acid to glycine (Asp30Gly)… 16/24
Models of how #SARSCoV2 bind to #ACE2 suggest that having a glycine at the 30th residue might significantly reduce binding efficiency. That could mean a reduced probability of infection upon exposure to the virus… 17/24
Importantly, aside from individual green monkeys with the Asp30Gly variant, it looks like (based on genetic variation underlying protein structure and function) savanna monkeys in general are as susceptible as we are to #SARSCoV2 infection (now confirmed in captivity)… 18/24
Also now confirmed: captive green monkeys will be good models for #SARSCoV2 vaccine & therapy development. Given 36% of the green monkeys we assessed at @wakehealth also have the Asp30Gly variant, we could also test what effect that variant might have on viral binding… 19/24
I want to repeat: we don’t know for sure yet if savanna monkeys become infected or sick in the wild. And we don’t know, if they became sick, whether they would be infectious to humans. But the possibility exists. This needs to assessed by testing wild monkeys… 20/24
However, these data suggest that we should be cautious and try NOT to expose savanna monkeys to human infections! 21/24
Fatal anthroponotic/zoonotic cycles have been seen before in primates (for example, concurrent Ebola epidemics in African apes and nearby human populations), so again we should be cautious to prevent exposure…. 22/24 https://onlinelibrary.wiley.com/doi/abs/10.1111/mam.12082">https://onlinelibrary.wiley.com/doi/abs/1...
Ultimately, we suggest, as others have before us, that monitoring wild NHP health could be vital to a #OneHealth approach to understanding #COVID19 that also centers the conservation of monkeys and apes near human epidemics… 23/24
https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajpa.20949">https://onlinelibrary.wiley.com/doi/pdf/1...
https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajpa.20949">https://onlinelibrary.wiley.com/doi/pdf/1...
This approach may not only save human lives, but also the lives/well-being of co-resident non-human primates. In the case of fatal zoonoses, like #COVID19, further study of the health of our local animal populations can benefit both us and them. 24/24
fin, thanks for reading!
fin, thanks for reading!
