Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense

[Treyfish]

ACCEPTED MANUSCRIPT
Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense

Xuhua Xia
Molecular Biology and Evolution, msaa094, https://doi.org/10.1093/molbev/msaa094
Published:

14 April 2020
Article history
Split View

• Cite
• Permissions Icon Permissions
• Share

Abstract

Wild mammalian species, including bats, constitute the natural reservoir of Betacoronavirus (including SARS, MERS, and the deadly SARS-CoV-2).

Different hosts or host tissues provide different cellular environments, especially different antiviral and RNA modification activities that can alter RNA modification signatures observed in the viral RNA genome. The zinc finger antiviral protein (ZAP) binds specifically to CpG dinucleotides and recruits other proteins to degrade a variety of viral RNA genomes. Many mammalian RNA viruses have evolved CpG deficiency. Increasing CpG dinucleotides in these low-CpG viral genomes in the presence of ZAP consistently leads to decreased viral replication and virulence.

Because ZAP exhibits tissue-specific expression, viruses infecting different tissues are expected to have different CpG signatures, suggesting a means to identify viral tissue-switching events. I show that SARS-CoV-2 has the most extreme CpG deficiency in all known Betacoronavirus genomes. This suggests that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high ZAP expression.
A survey of CpG deficiency in viral genomes identified a virulent canine coronavirus (Alphacoronavirus) as possessing the most extreme CpG deficiency, comparable to that observed in SARS-CoV-2. This suggests that the canine tissue infected by the canine coronavirus may provide a cellular environment strongly selecting against CpG. Thus, viral surveys focused on decreasing CpG in viral RNA genomes may provide important clues about the selective environments and viral defenses in the original hosts.
SARS-CoV-2, viral evolution, canine intestine, zinc finger antiviral protein, COVID-19
Issue Section:
Letter
Associate Editor: Sudhir KumPDF
This content is only available as a PDF.:tiphat:https://academic.oup.com/mbe/article...saa094/5819559

 

[Treyfish]

Coronavirus: Stray dogs eating bat meat could have sparked pandemic, scientist claims


Other researchers have rejected the findings and say dog owners do not need to be concerned

• Chris Baynes
• 43 minutes ago
• Covid-19 could have been transmitted to humans by stray dogs which had eaten bat meat, according to a study.
  
  The disease may have rapidly evolved in the intestines of dogs that consumed bats carrying an ancestor coronavirus, a Canadian biologist has proposed.
  ...This theory has now been disputed by Xuhua Xia, a biology professor at the University of Ottawa who examined more than 1,250 genomes from the same coronavirus family as Sars-CoV-2.
• Prof Xia, who specialises in using data to study molecular evolution of genes, concluded the virus strains isolated in snakes and pangolins diverged too far from Sars-CoV-2 for those animals to be the missing link in the disease’s journey from bats to humans.
  
  “Our observations have allowed the formation of a new hypothesis for the origin and initial transmission of Sars-CoV-2,” he said. “The ancestor of Sars-CoV-2 and its nearest relative, a bat coronavirus, infected the intestine of canids, most likely resulting in a rapid evolution of the virus in canids and its jump into humans. .... https://www.independent.co.uk/news/s...-a9465141.html

 

[Emily]

[ETA Emily: removed judgemental comment that was based on media distortion.]

https://www.outlookindia.com/website...hua-xia/350782

Q) Does this also raise the necessity of culling stray dogs?

No. One should test rectal swabs of stray dogs for the presence of SARS-CoV-2 before taking measures against them. If we decide to exterminate stray dogs, we not only miss an opportunity of detecting various viruses in stray dogs, but also commit unjustified brutality against these animals.

[ETA Emily: removed judgemental comment that was based on media distortion.]

https://www.livescience.com/did-coro...fter-bats.html
New study suggests COVID-19 hopped from dogs to humans. Here's why you should be skeptical.
By Nicoletta Lanese - Staff Writer 14 April 2020

 

[Emily]

Xia says his research is being abused by the media. I agree that the titles of media articles and this thread do not convey his position.

https://flutrackers.com/forum/forum/...cent-mbe-paper

ETA by Emily: Comment on thread title no longer relavant.

 

[Treyfish]

ACCEPTED MANUSCRIPT
Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host antiviral defense

Xuhua Xia
Molecular Biology and Evolution, msaa094, https://doi.org/10.1093/molbev/msaa094
Published:

14 April 2020
Article history
Split View

• Cite
• Permissions Icon Permissions
• Share

Abstract

Wild mammalian species, including bats, constitute the natural reservoir of Betacoronavirus (including SARS, MERS, and the deadly SARS-CoV-2).

Different hosts or host tissues provide different cellular environments, especially different antiviral and RNA modification activities that can alter RNA modification signatures observed in the viral RNA genome. The zinc finger antiviral protein (ZAP) binds specifically to CpG dinucleotides and recruits other proteins to degrade a variety of viral RNA genomes. Many mammalian RNA viruses have evolved CpG deficiency. Increasing CpG dinucleotides in these low-CpG viral genomes in the presence of ZAP consistently leads to decreased viral replication and virulence.

Because ZAP exhibits tissue-specific expression, viruses infecting different tissues are expected to have different CpG signatures, suggesting a means to identify viral tissue-switching events. I show that SARS-CoV-2 has the most extreme CpG deficiency in all known Betacoronavirus genomes. This suggests that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high ZAP expression.
A survey of CpG deficiency in viral genomes identified a virulent canine coronavirus (Alphacoronavirus) as possessing the most extreme CpG deficiency, comparable to that observed in SARS-CoV-2. This suggests that the canine tissue infected by the canine coronavirus may provide a cellular environment strongly selecting against CpG. Thus, viral surveys focused on decreasing CpG in viral RNA genomes may provide important clues about the selective environments and viral defenses in the original hosts.
SARS-CoV-2, viral evolution, canine intestine, zinc finger antiviral protein, COVID-19
Issue Section:
Letter
Associate Editor: Sudhir KumPDF
This content is only available as a PDF.:tiphat:https://academic.oup.com/mbe/article...saa094/5819559

 

[Treyfish]

From Bats To Humans: What Role Did Stray Dogs Play In Wuhan's SARS-CoV-2 Pandemic?
By News Staff |
April 15th 2020 09:19 AM |

Science is often easy in hindsight and two years from now we will likely know the evolution of SARS-CoV-2 from bats to humans. For now, it is mostly speculation.

An intermediate animal host may have been snakes or pangolins, but the real common ancestor of SARS-CoV-2 goes back for as long as coronavirus was recognized as distinct from the common cold - the 1960s.

A recent analysis links SARS-CoV-2, the official name for the 2019 coronavirus that can cause the COVID-19 disease, to dog intestines. There is no secret that Wuhan's wet markets - disgusting confluences of feces, urine, and blood where live animals, dead animals, and produce are all in close contact with little hygiene - caused its early spread in the city. But the ancestor of SARS-CoV-2 and its nearest relative, the recent bat coronavirus, infected the intestine of canids.

Humans and mammals have a key antiviral sentinel protein, called ZAP,...:tiphat:https://www.science20.com/news_staff...andemic-247230

 

[Emily]

No author name or background? This is exactly the misuse of his work that Xia is protesting: https://flutrackers.com/forum/forum...a-xia-new-media-distorted-my-recent-mbe-paper

 

[Emily]

"This suggests that the canine tissue infected by the canine coronavirus may provide a cellular environment strongly selecting against CpG."
That is a FAR cry from the [titles of some media stories like "Coronavirus 'was spread to humans by dogs', scientists claim"]
That is the kind of new media distortion he is trying to correct.

http://dambe.bio.uottawa.ca/publications/Q_A.pdf
"2. Does the paper have limitations?
Yes. As I have mentioned before, if we have data from all mammalian species and all tissues, and only canine digestive system harbors coronaviruses with a low CpG genome, then canids would be implicated as a strong candidate contributing to the evolution of low CpG in SARS-CoV-2. However, because we are far from having all data from all mammals and all mammalian tissues, the suggestion of canids as a possible host species is speculative. I have discussed this in the paper."

 

[Treyfish]

:tiphat:https://www.science20.com/contributors

 

[Emily]

OK, which of that huge lineup wrote the article? Ane why does the title of this thread still state as fact what Xia is protesting as misinformation? This scientist being misquoted does not seem to want to recklessly endanger dogs. Do we want to do that?
https://www.linkedin.com/pulse/much-misunderstanding-arising-from-my-recent-mbe-paper-xuhua-xia

 

[Treyfish]

i can delete the thread. I posted it as another of the 40 theories out there which is actually what the guy says, dogs may have carried it or helped spread it. I dont think its a big worry that people would be running out and killing dogs. CHINA is the ones eating dogs and now a second city officially takes them off the menu. I have only seen one dog that was beaten to death, by the chinese, 3 months ago. i havent seen any other reports of people running from or hurting stray dogs. Im glad china is taking dogs off the menu, they may even had a role in the outbreak/? I can put his post at the top or leave it or delete it.

 

[Emily]

No need to delete thread as far as I am concerned. We should know what is being said and reported. Thanks VERY much for changing the title, though. :applause:

 

[Treyfish]

.....Stray dogs may be the intermediate hosts for the novel coronavirus, facilitating its jump from animals to humans, according to a new analysis by Xuhua Xia. Xia is a professor in the Department of Biology at The University of Ottawa.

Xia's researchposes a genetic explanation for the theory that stray dogs carried SARS-CoV-2 to humans.

Dogs' intestinal tracts create a perfect environment to shape the genome of the coronavirus, allowing it to evolve to infect humans, Xia suggests. The argument boils down to a single dinucleotide in the viruses' genome called CpG dinucleotide. As Xia notes in the paper, SARS-CoV-2 has the "most extreme deficiency" of the molecule amongst all known betacoronaviruses.
hat absence signaled to Xia that there could be some evolutionary reason that this dinucleotide was missing from the viral genome.

Previous studies have shown that CpG acts as a landing pad for a protein called ZAP, which, in mammals, targets viruses and chops up their genomes. Interestingly, studies on HIV (a single-stranded RNA virus like SARS-CoV-2) show that when is CpG increases, the virus fails to replicate.

SARS-CoV-2 may have, at some point, dwelt in a host with high ZAP proteins, which in turn, caused the virus to lose CpG dinucleotides as it evolved in that environment. Xia's paper suggests that the canine digestive system, which is rich in ZAP proteins, is an obvious candidate.
The theory is detailed in a paper published Tuesday in the journal Molecular Biology and Evolution.....

BAD NEWS FOR GOOD BOYS? — This is just one study. When Inverse spoke to Xia, he cautioned that scientists need to look for potential coronavirus evolution in many more animal species, not just the usual suspects, like bats.

"It is relevant that in the future surveillance programs should include canine species," Xia tells Inverse.

"If we have sampled all the mammalian tissues and the canine species is the only one that favors the origin of SARS-CoV-2, then we can very well conclude that the canine digestive system is probably key contributor to the evolution of SARS coronavirus."
DOGS AREN'T GOOD HOSTS – In a study published in Science last week, scientists tested infecting dogs with SARS-CoV-2 in the lab.

They found that the novel coronavirus struggled to replicate in dogs compared to cats. In our feline friends, the virus was able to flourish in the respiratory system, but not the lungs.

The results suggest that a dog's body is not particularly homey for the coronavirus.

"People have tried infecting dogs with SARS-CoV-2 and they're not efficiently infected so the idea that they're an intermediate host, I don't think, is correct either," Racaniello says.

Xia points out that the Science study leaves some questions unanswered. His work suggests that the dog digestive tract is one potential, ancestral home for the coronavirus. And in the Science study, rectal swaps taken from two of the beagles exposed to virus did contain viral RNA. But the virus wasn't found in any other tissues.

As of publishing, the United States' Centers for Disease Control and Prevention website offers comfort for those of us who might worry about our own furry companions, let alone the millions of stray Good Boys around the world.....:tiphat:https://www.inverse.com/science/can-...ad-coronavirus

 

[Treyfish]

....How the virus ended up in humans?


Canid behavior includes licking anal and genital regions, which is not only found during mating but in other circumstances as well. This may indeed facilitate viral transmission from the gastrointestinal system to the respiratory tract, as well as subsequent switch from gastrointestinal to a respiratory pathogen.

Based on the study results, the authors present a scenario where the coronavirus initially spread from bats to stray dogs consuming bat meat. Afterward, presumed strong selection against CpG in the viral genome while infecting dogs' intestines gave rise to rapid viral evolution towards reduced genomic CpG. Ultimately, such reduced CpG trait allowed the virus to evade human immune response mediated by ZAP and, thus, to become a severe human pathogen that we are faced with today.

"While the specific origins of SARS-CoV-2 are of vital interest in the current world health crisis, this study more broadly suggests that important evidence of viral evolution can be revealed by consideration of the interaction of host defenses with viral genomes, including selective pressure exerted by host tissues on viral genome composition", concludes Dr. Xia.:tiphat:https://www.news-medical.net/news/20...-pandemic.aspx​

 

[Treyfish]

Study claims stray dogs sparked pandemic

However, University of Cambridge Department of Veterinary Medicine head debunks work and insists owners should not be concerned by findings.
James Westgate April 15, 2020

Single strand


Prof Xia hypothesised that the ancestor of the new coronavirus and its nearest relative – a bat coronavirus – infected the intestines of dogs, where it evolved before jumping to humans.
....
Similarities


In his study, Prof Xia analysed all 1,252 full-length betacoronavirus genomes deposited into the open access GenBank database.

He said SARS-CoV-2 and its closest known relative – a bat coronavirus (BatCoV RaTG13) sharing 96% sequence similarity – have the lowest amount of CpG among its close coronavirus relatives.

Only genomes from canine coronaviruses, which have already caused a highly contagious intestinal disease worldwide in dogs, have similar genomic values...

However, the paper was criticised by University of Cambridge Department of Veterinary Medicine head and researcher in infection dynamics, James Wood.

Prof Wood said: “I find it difficult to understand how the author has been able to conclude anything from this study, or to hypothesise much, let alone that the virus causing COVID-19 may have evolved through dogs.

“There is far too much inference and far too little direct data. I do not see anything in this paper to support this supposition and am concerned this paper has been published in this journal.

“I do not believe any dog owners should be concerned as a result of this work.”:tiphat:https://www.vettimes.co.uk/news/stud...rked-pandemic/

 

[Treyfish]

:tiphat:They will NEVER stop eating dogs,cats,rats,horses,snakes,monkeys,bats,turtles,cievet cats,....NO MATTER WHAT THEY SAY!!!

Second city in China bans consumption of dogs and cats in wake of coronavirus


By Natalie O'Neill

April 15, 2020 | 6:04pm


Chowing down on man’s best friend has become illegal in another Chinese city in the wake of the global coronavirus pandemic.

The southern metropolis of Zhuhai has become the second city in the country to permanently ban the consumption of dog and cat meat, Newsweek reported Wednesday. The southeastern Chinese city of Shenzhen became the first city to ban the controversial practice earlier this month.

The two cities will enforce the ban from May 1, the outlet reported...:tiphat:https://nypost.com/2020/04/15/second...f-coronavirus/

 

[sharon sanders]

Ok...to clear something up. China has officially discouraged eating cats and dogs for about 10 years. However, the practice still persists in some places. If people are eating cats and dogs again it is probably because they need the source of meat. This practice re-started before COVID-19 became a huge problem. I think more linked to the swine fever and lack of pork.

China - Cats on the menu still - November 9, 2019

China - Taiwan media report of increased dog meat consumption on mainland - October 22, 2019

 

[bertrand789]

Ce n'est pas pour rien qu'un v?t?rinaire, comme moi, demande que les faits soient produits. Quand on souhaite apprendre les possibles chez les animaux, on commence par vous faire entrevoir le normal, ensuite certains se sp?cialisent, exemple en parasitologie. Pour voir l'impensable, il suffit d'aller dans des zoos ou lieux de commerce d'animaux multi-esp?ces.
Dans tous les lieux de d?tention, et ou, de commerce de x animaux dans des conditions souvent douteuses, bien de ce que l'on n'imagine pas peut ?tre. Que l'on stoppe en attente de produire les faits soit, mais cela veut aussi dire qu'ensuite on doit aller voir et pas qu'en Chine...

Comme le pangolin, les chauves souris, les furets, sont des potentiels, quid des r?sultats des pr?l?vements en bien des lieux en Chine, comme ailleurs . On ne trouve rien sur les furets de NY ?

Pour la petite histoire, l'?cole v?t?rinaire de Maison Alfort est le lieu ou suite au d?ploiement de la motorisation, on a cherch? ? valoriser les chevaux en fin de carri?re. On y a cr?? un ?levage de porcs nourris avec les cadavres des chevaux. Les ?tudiants v?t?rinaires de l'?poque trouvait que la viande issue de cet ?levage n'avait pas un bon go?t ... J'ai cherch?, mais je n'ai jamais vu les pr?l?vements fait sur cet ?levage. Heureusement, la cuisson, cela peut faire bien des choses...

Que les v?t?rinaires chinois soient officiellement missionn?s ? faire leur travail serait un peu rassurant. Mais pour se faire, il faut certes les missionner, mais aussi leur donner les moyens de faire les analyses.

Donc moins de blouse blanche et plus de blouse bleue. Ceci signifie, plus d'humains form?s qui vont voir et d?crire la r?alit? que de personnes dans des laboratoires qui font des sp?culations ou des sondages par tel ...

Pour rappel, j'avais ?crit 0 pr?l?vements sur 4 000 000 de chats consomm?s, cela est anormal en Chine, mais ils ont fait quoi au Vietnam etc ?

 

[Treyfish]

Ce n'est pas pour rien qu'un v?t?rinaire, comme moi, demande que les faits soient produits. Quand on souhaite apprendre les possibles chez les animaux, on commence par vous faire entrevoir le normal, ensuite certains se sp?cialisent, exemple en parasitologie. Pour voir l'impensable, il suffit d'aller dans des zoos ou lieux de commerce d'animaux multi-esp?ces.
Dans tous les lieux de d?tention, et ou, de commerce de x animaux dans des conditions souvent douteuses, bien de ce que l'on n'imagine pas peut ?tre. Que l'on stoppe en attente de produire les faits soit, mais cela veut aussi dire qu'ensuite on doit aller voir et pas qu'en Chine...

Comme le pangolin, les chauves souris, les furets, sont des potentiels, quid des r?sultats des pr?l?vements en bien des lieux en Chine, comme ailleurs . On ne trouve rien sur les furets de NY ?

Pour la petite histoire, l'?cole v?t?rinaire de Maison Alfort est le lieu ou suite au d?ploiement de la motorisation, on a cherch? ? valoriser les chevaux en fin de carri?re. On y a cr?? un ?levage de porcs nourris avec les cadavres des chevaux. Les ?tudiants v?t?rinaires de l'?poque trouvait que la viande issue de cet ?levage n'avait pas un bon go?t ... J'ai cherch?, mais je n'ai jamais vu les pr?l?vements fait sur cet ?levage. Heureusement, la cuisson, cela peut faire bien des choses...

Que les v?t?rinaires chinois soient officiellement missionn?s ? faire leur travail serait un peu rassurant. Mais pour se faire, il faut certes les missionner, mais aussi leur donner les moyens de faire les analyses.

Donc moins de blouse blanche et plus de blouse bleue. Ceci signifie, plus d'humains form?s qui vont voir et d?crire la r?alit? que de personnes dans des laboratoires qui font des sp?culations ou des sondages par tel ...

Pour rappel, j'avais ?crit 0 pr?l?vements sur 4 000 000 de chats consomm?s, cela est anormal en Chine, mais ils ont fait quoi au Vietnam etc ?

:tiphat:It is not for nothing that a veterinarian, like me, demands that the facts be produced. When we want to learn the possibilities in animals, we start by making you glimpse the normal, then some specialize, for example in parasitology. To see the unthinkable, just go to zoos or places where you can trade in multi-species animals.
In all places of detention, and or, of trade in x animals in often doubtful conditions, much of what one does not imagine can be. That we stop waiting to produce the facts either, but that also means that then we must go to see and not that in China ...

Like the pangolin, bats, ferrets, are potentials, what about the results of samples in many places in China, as elsewhere. Can't find anything on NY ferrets?

For the record, the Maison Alfort veterinary school is the place where, following the deployment of motorization, we sought to promote horses at the end of their careers. We have created a pig farm fed with the corpses of horses. Veterinary students of the time found that the meat from this farm did not taste good ... I looked for it, but I never saw the samples taken on this farm. Fortunately, cooking can do many things ...

It would be a little reassuring if Chinese veterinarians were officially commissioned to do their job. But to do so, it is certainly necessary to mission them, but also to give them the means to make the analyzes.

So less white blouse and more blue blouse. This means, more trained humans who will see and describe reality than people in laboratories who make speculations or polls by such ...

As a reminder, I wrote 0 samples out of 4,000,000 cats consumed, this is abnormal in China, but what did they do in Vietnam etc?

 

[Treyfish]

Coronavirus causes surge in dog and cat meat sales in Vietnam and Cambodia, investigators say


Stop the Wildlife Trade: Even doctors sometimes recommend it in false belief it protects against viruses and heals scars

• Jane Dalton @JournoJane
• 5 minutes ago

Sales of dog and cat meat have risen in Vietnam and Cambodia since the outbreak of the coronavirus because people believe it has “warming” properties that head off flu viruses, an investigation has found.

Even some hospital doctors recommend the meat to patients, claiming it helps protect them from cold weather and recover from surgery, according to campaigners.

But experts say caging the animals in large numbers and slaughtering them in insanitary conditions actively increases the chances of starting dangerous diseases, and there is no evidence of the meat having any beneficial effects.
The trade is part of the “ticking time bomb” of live animal markets strongly thought to have sparked the pandemic and could spark another one, they warn.
.......
Covid-19 has also led to a sudden hike in dog and cat meat dishes being advertised on food delivery apps as restaurants in Vietnam switch to takeaway services.
Meat buyers in both Cambodia and Vietnam told the investigators that the World Health Organisation's announcement on cats and dogs not catching the virus prompted people to think that eating them was safe.....

“The insanitary conditions of the cat and dog meat trade, coupled with the contamination risks of having so many different animal species caged and killed alongside one another, present the perfect breeding ground for new and deadly diseases, like Covid-19.:tiphat:https://www.independent.co.uk/news/w...-a9464946.html