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FactCheck Posts › SciCheck


POSTS MISREPRESENT MOUSE STUDY OF PANGOLIN VIRUS

By Kate Yandell

Posted on February 2, 2024

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SCICHECK DIGEST

A study showed a type of lab mouse is highly susceptible to a coronavirus
derived from pangolins, a scaly, cat-sized mammal. This doesn’t mean the virus
is dangerous to humans. The virus is related to the one that causes COVID-19 but
did not descend from it, contrary to claims that it is a “mutant COVID-19
strain.” Nor did scientists “craft” the virus.

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FULL STORY

Biologists sometimes work with lab mice engineered to have human-like tissues,
cells or genes. Researchers studying viruses may use mice that have been
genetically modified to have human receptors on their cells that allow entry of
viruses that infect humans.

While these “humanized” mice can give insights into viruses and what treatments
or vaccines might work against them, the mice are not that similar to humans. A
virus that kills a humanized mouse will not necessarily be dangerous to people.



A recent study of a version of a pangolin virus in one of these modified mouse
models has been misrepresented. Pangolins are mammals prized in Asia for their
meat and unusual scales. A preliminary version of the study was posted Jan. 4 as
a preprint that has not been peer-reviewed. The researchers posted an
updated preprint on Jan. 21 in response to widespread misinterpretations of
their work.

“Chinese lab crafts mutant COVID-19 strain with 100% kill rate in ‘humanized’
mice: ‘Surprisingly’ rapid death,” said the headline of a Jan. 16 New York
Post story.

“Chinese scientists ‘create’ a mutant coronavirus strain that attacks the BRAIN
and has a 100% kill rate in mice – as they admit there’s a ‘risk it spills over
to humans,’” read the headline of a Daily Mail story published the same day.
Various versions of these claims have spread widely on social media.

Photo of a pangolin by Doloh / stock.adobe.com

In reality, the researchers looked at GX_P2V, a virus found in pangolins. When
they infected four mice modified to produce certain human receptors, the virus
killed the mice. But co-author Lihua Song, a researcher at Beijing University of
Chemical Technology, clarified that the study did not mean the virus was
dangerous to people. 

The mice used in the experiments “are unique and do not exist in nature,”
Song wrote in a Jan. 17 comment on the preprint server where the study was
posted. “The outcomes from these tests cannot be applicable to humans.” 

There are many different types of coronaviruses. The coronavirus used in the
study is in the same family as SARS-CoV-2, the coronavirus that causes COVID-19,
but it is incorrect to say that the virus in the study is a “mutant COVID-19
strain,” as it is not descended from SARS-CoV-2. 

Nor did the authors of the study “craft” or “create” the version of GX_P2V they
used to infect the mice. The virus used in the study was not engineered by
scientists and had been previously described. The researchers explained in the
updated preprint that the new findings do not alter their fundamental impression
that the virus is relatively weak, or attenuated.


MOUSE CHARACTERISTICS EXPLAIN WHY VIRUS WAS LETHAL

The researchers hypothesized in the updated preprint that GX_P2V had proven so
lethal in the mice because they had been engineered to be unusually susceptible
to infection in their brains. They noted that humans or normal mice, for that
matter, would not be expected to be similarly susceptible.

To enter cells, viruses need to glom onto specific receptors. GX_P2V, like
SARS-CoV-2, enters cells using ACE2 receptors. Many different types of animals
have ACE2 receptors. To better understand viral infection in humans, researchers
sometimes engineer mice to produce human ACE2 receptors.

In a previous study in mice with human ACE2 receptors, GX_P2V had limited
ability to sicken the mice. But the mice used in the new study had been
engineered to produce large quantities of human ACE2 across multiple tissues,
including the brain, according to the preprint. ACE2 levels are lower in human
brains, the researchers wrote.

The mice in the study “are cranking out massive levels of ACE2 on pretty much
every cell in the body so they are getting infected with much higher levels of
virus in more organs than a human would,” said Angela Rasmussen, a virologist at
the University of Saskatchewan’s Vaccine and Infectious Disease Organization, in
a Jan. 19 thread on X, formerly known as Twitter. The animals died because they
had been engineered “to support massive virus growth,” she said. 


RESEARCHERS DID NOT ‘CRAFT’ NEW VIRUS

GX_P2V was originally isolated from a pangolin — which had been seized in an
anti-smuggling operation — in 2017 by a different group of researchers. The
virus was described in a 2020 paper published in Nature. The researchers grew it
in cells, but the version this yielded — dubbed GX_P2V(short_3UTR) —
was slightly different from the version originally isolated from the pangolin.

Rasmussen explained on X that it is common for an RNA virus like GX_P2V to
change as it grows in cell culture. “It’s not unexpected and usually is
attenuating,” she said, meaning the viruses become less virulent. 

The virus used in the study did not result from engineering or any kind of
intentional manipulation, but rather “occurred in the normal course of isolating
this virus through classic virological techniques,” she said.

Song, the preprint co-author, told FactCheck.org via email that he and his
colleagues were in fact trying to investigate whether the GX_P2V variant could
itself be used as a vaccine to protect broadly against SARS-CoV-2 strains. There
has been interest in developing vaccines that would protect against a greater
variety of SARS-CoV-2 variants, including future variants. 

Song said that the GX_P2V variant appeared promising as a vaccine candidate
because in prior research it had been identified as “highly attenuated across
various animal species,” meaning that it did not significantly sicken the
animals.

Song said the researchers gave the mice the virus primarily to see what kind of
immune response it generated. He said the discovery that the virus was lethal to
the modified mice “was unforeseen” and presented new ideas for how the modified
mice and the virus could be used in research. 

Researchers could vaccinate the mice with a prospective COVID-19 vaccine and
then expose them to the GX_P2V variant, he suggested. This could help them
assess whether the vaccine could provide broad protection. Song also said the
model is unique because the virus replicated and killed the mice without causing
the inflammation that comes with a SARS-CoV-2 infection. He said researchers
could use the model to test how well antiviral drugs suppress viral replication.

In the original preprint, the researchers had written that the work “underscores
a spillover risk of GX_P2V into humans.” They removed this statement in the
subsequent version.

Song said the original phrasing was based on the thought that the experiment
“corroborated earlier findings that GX_P2V can indeed utilize human ACE2 for
infections, which led me to suggest a potential, albeit theoretical, risk of
transmission into humans.” 

But, he said, the phrasing “unintentionally misguided readers into believing
there was a potential risk of the virus spilling over into human brains and
causing 100% fatality, which is not accurate.”

Furthermore, he explained, scientists who read the preprint pointed out there
currently isn’t empirical evidence indicating spillover risk to humans. “While
it has been demonstrated in prior research that this virus can bind to the human
ACE2 receptor, assessing spillover risks involves a broader evaluation than just
the receptor interaction,” he said.


MISREPRESENTATIONS MORPH INTO CONSPIRACY THEORIES

As we’ve said, the authors of the preprint did not create a new virus or cause a
virus to become more harmful.

Despite these facts, posts spun unsubstantiated theories about a new disease.
Some posts mashed up claims about the mouse study with references to Disease X —
a placeholder name for potential future pandemic threats that has been co-opted
to support conspiracy theories.

“There’s gonna be a new covid -19 stran coming soon called dease-x It 100% kills
you with 8 days !!!” read one post, mixing up multiple unsupported claims.

Other posts referred to the work as gain-of-function research. “So the gain of
function research is not just a gain of function for the coronavirus, it’s a
gain of function for the totalitarian Empire virus,” read one post, arguing that
the creation of new viruses “consolidates the power of State.”

Song denied that his study constituted gain-of-function research in a comment on
the preprint. “There have been some folks trying to misinterpret our work as
gain-of-function research,” he said. “Let me be clear – that is not the case.”

There are various definitions of gain-of-function research, which
most broadly just refers to research in which an organism gains some new
ability. More narrow definitions attempt to focus on a subset of
gain-of-function research that could be risky.

The U.S. government defines one such subset, called enhanced potential pandemic
pathogen research, as work that is “reasonably anticipated to create, transfer
or use potential pandemic pathogens resulting from the enhancement of a
pathogen’s transmissibility and/or virulence in humans.” 

Rasmussen agreed on X that Song’s study was not gain-of-function research,
referring to the latter definition. This was both because the GX_P2V variant was
not engineered or produced intentionally, and because the virus “didn’t cause
much disease in hamsters” and couldn’t be “reasonably anticipated” to cause
severe disease.

She said that it is valid to have varying opinions of risks posed by virus
research but objected to fearmongering and unsupported criticisms.

“The reason why this was so deadly in these particular mice is because they are
engineered to support massive virus growth,” Rasmussen said. “There is a gain of
function in the mice—high levels of human ACE2 everywhere—not the virus.”

--------------------------------------------------------------------------------

Editor’s note: SciCheck’s articles providing accurate health information and
correcting health misinformation are made possible by a grant from the Robert
Wood Johnson Foundation. The foundation has no control over FactCheck.org’s
editorial decisions, and the views expressed in our articles do not necessarily
reflect the views of the foundation.


SOURCES

“Why humanized mice?” Jackson Lab website. 21 Jul 2020.

Gurumurthy, Channabasavaiah B. et al. “Genetically Modified Mouse Models to Help
Fight COVID-19.” Nature Protocols. 26 Oct 2020.

United Nations Office on Drugs and Crime. “World Wildlife Crime Report 2020.”
UNODC website. May 2020.

Wei, Lai et al. “Lethal Infection of Human ACE2-Transgenic Mice Caused by
SARS-CoV-2-Related Pangolin Coronavirus GX_P2V(short_3UTR).” bioRxiv. 4 Jan
2024.

Wei, Lai et al. “An Infection and Pathogenesis Mouse Model of SARS-CoV-2-Related
Pangolin Coronavirus GX_P2V(short_3UTR).” bioRxiv. 21 Jan 2024. 

Donlevy, Katherine et al. “Chinese lab crafts mutant COVID-19 strain with 100%
kill rate in ‘humanized’ mice: ‘Surprisingly’ rapid death.” 16 Jan 2024. Updated
17 Jan 2024.

Tilley, Caitlin. “Chinese scientists ‘create’ a mutant coronavirus strain that
attacks the BRAIN and has a 100% kill rate in mice – as they admit there’s a
‘risk it spills over to humans’.” Daily Mail. 16 Jan 2024. Updated 18 Jan 2024.

Being Libertarian (@beingalibertarian). “Any guesses as to who is funding this?”
Instagram. 16 Jan 2024.

Al-Ghaili, Hashem. “‘Chinese scientists are experimenting with a mutant COVID-19
strain that is 100% lethal to “humanized” mice.’” Facebook. 17 Jan 2024.

William Copus (@thefeedski). “Chinese Scientists have created a new COVID strain
that attacks the brain and is 100% lethal and experts around the world are
urging them to stop.” Instagram. 17 Jan 2024.

Wes Austin | Lawyer | Comedian (@wesley.austin2). “Chinese Lab Makes Mutant
Strain with 100% Kill Rate in Humanized Mice #reels #reelsvideo #reelsinstagram
#instareels #instavideo #instagood.” Instagram. 18 Jan 2024.

NewsNation (@newsnationnow). “Chinese scientists are experimenting with a mutant
strain of COVID that reportedly has a 100% mortality rate in mice.” Instagram.
18 Jan 2024.

Business | Motivation | Mindset (@theamazingmindset). “Chinese scientists are
experimenting with a mutant COVID-19 strain that is 100% lethal to ‘humanized’
mice. …” Instagram. 18 Jan 2024.

Erica Meier| Pharma Skeptic (@truth.seekingmama). “There plan is to depopulate.
…” Instagram. 20 Jan 2024.

RICHIE THE BARBER (@richiethebarber). “There’s gonna be a new covid -19 stran
coming soon called dease-x It 100% kills you with 8 days !!!” Instagram. 23 Jan
2024.

Song, Lihua. Emails with FactCheck.org. 31 Jan 2024.

Jaramillo, Catalina. “Video Distorts Early Coronavirus Research To Promote
Baseless Bioweapon Conspiracy Theory.” FactCheck.org. 15 Jun 2023.

Lu, Shanshan et al. “Induction of Significant Neutralizing Antibodies against
SARS-CoV-2 by a Highly Attenuated Pangolin Coronavirus Variant with a 104nt
Deletion at the 3’-UTR.” Emerging Microbes & Infections. 18 Dec 2022.

Grove, Joe and Marsh, Mark. “The Cell Biology of Receptor-Mediated Virus Entry.”
The Journal of Cell Biology. 28 Nov 2011.

Niu, Sheng et al. “Molecular Basis of Cross‐species ACE2 Interactions with
SARS‐CoV‐2‐like Viruses of Pangolin Origin.” The EMBO Journal. 8 Jun 2021.

Liu, Mei-Qin et al. “A SARS-CoV-2-Related Virus from Malayan Pangolin Causes
Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.” Journal of
Virology. 23 Jan 2023.

Dr. Angela Rasmussen (@angie_rasmussen). “… This article and others like it are
very misleading. This was not gain-of-function research, no matter how many loud
non-experts say it is. …” X. 10 Jan 2024.

Lam, Tommy Tsan-Yuk et al. “Identifying SARS-CoV-2-Related Coronaviruses in
Malayan Pangolins.” Nature. 26 Mar 2020.

DiedSuddenly (@DiedSuddenly_). “Reports out of China are saying that a new
disease X is emerging with a 100% kill rate on the lab tested mice. At the same
time, China is assembling mobile crematoriums. How do you interpret this?” X. 14
Jan 2024.

Spencer, Saranac Hale. “Posts Misrepresent WHO Term ‘Disease X’ for Possible
Future Illness.” FactCheck.org, 26 Jan 2024. 

Family Research Council (@frcdc). “‘Quite alarming.’ Dr. Robert Malone joined
Tony Perkins on Washington Watch to unpack reports of Chinese Scientists using
gain-of-function research to develop a new, deadly strain of COVID. …”
Instagram. 18 Jan 2024.

Aubrey Marcus (@aubreymarcus). “As long as there is gain-of-function research
going on anywhere in the world, we are going to be exposed to new viruses. …”
Instagram. 16 Jan 2024.

Kuiken, Todd. “Global Pandemics: Gain-of-Function Research of Concern.”
Congressional Research Service report. 21 Nov 2022.

“Research Involving Enhanced Potential Pandemic Pathogens.” NIH website. 5 Jun
2023.

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