New brain virus

6 months ago

Lethal Infection of Human ACE2-Transgenic Mice Caused by SARS-CoV-2- related Pangolin Coronavirus GX_P2V(short_3UTR)

4th January 2024

SARS-CoV-2-related pangolin coronavirus GX_P2V can cause 100% mortality in human ACE2-transgenic mice,

potentially attributable to late-stage brain infection.

This underscores a spillover risk of GX_P2V into humans,

and provides a unique model for understanding the pathogenic mechanisms of SARS-CoV-2-related viruses.

Dear Editor,

Two SARS-CoV-2-related pangolin coronaviruses, GD/2019 and GX/2017,

were identified prior to the COVID-19 outbreak.
The respective isolates, were cultured in 2020 and 2017

the early passaged GX_P2V isolate was actually a cell culture-adapted mutant.

We assessed its pathogenicity in hACE2 mice.

We found that the GX_P2V clone can infect hACE2 mice,

with high viral loads detected in both lung and brain tissues.

This infection resulted in 100% mortality in the hACE2 mice.

We surmise that the cause of death may be linked to the occurrence of late brain infection.

All the mice that were infected with the live virus succumbed to the infection within 7-8 days post-inoculation,

rendering a mortality rate of 100%

5 days post-infection

decrease in body weight

7 days post-infection

piloerection, hunched posture, and sluggish movements, and their eyes turned white.

8 hACE2 mice were infected

8 mice inoculated with inactivated virus

8 mice mock-infected

Dissections on days 3 and 6

Quantitative analysis of viral RNA and titer.

Significant amounts of viral RNA in the brain, lung, turbinate, eye, and trachea

no or a low amount of viral RNA was detected in heart, liver, spleen, kidneys, tongue, stomach, and intestines.

Lung samples

High viral RNA loads on days 3 and 6 post-infection

Viral antigens also detected

Viral load in the lungs significantly decreased by day 6

Lungs showed minimal inflammation

Brain samples

Day 3 post-infection, viral RNA was detected in all infected mice,

shrunken neurons visible in cerebral cortex

Viral antigens also detected

Day 6 post-infection, exceptionally high viral RNA loads (∼ 8.5 Log10[copies/mg]) in the brain samples from all infected mice,

focal lymphocytic infiltration around the blood vessels.

Severe brain infection during the later stages of infection may be the key cause of death in these mice.

To the best of our knowledge, this is the first report showing that a SARS-CoV-2-related pangolin coronavirus can cause 100% mortality in hACE2 mice,

suggesting a risk for GX_P2V to spill over into humans.

Propensity of coronaviruses to undergo adaptive mutation during passage culture.

……. requires further investigation.

It is possible that GX_P2V C7 has undergone a virulence-enhancing mutation.

Justin Kinney, Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, U.S.

“The research is still very dangerous, though,”

“I am especially concerned that the paper does not say what biosafety level the work was performed at.

Coronavirus research in China is often done at a biosafety level (BSL-2) that is inadequate for working with potential pandemic pathogens that might be transmitted by air.

“Indeed, coronavirus research done at BSL-2 may have caused the COVID-19 pandemic.

And by showing that the coronavirus has a surprisingly high pathogenicity, the work underscores the need for extreme caution when working with novel coronaviruses.”

Lihua Song

did not respond to a request for comment on how the scientists ensured the experiments they performed were safe.

Yigang Tong

Trained in a Chinese military program and worked in military-run labs.

He also co-authored a paper in 2023 with Zheng-Li Shi, who helps run the Wuhan Institute of Virology.

Justin Goodman, senior vice president, White Coat Waste Project, a U.S. nonprofit

“dangerous and deadly tests on mice.”

“This is why shipping US tax dollars to foreign adversaries’ unaccountable animal labs is a recipe for disaster and we’re working with lawmakers to stop it,”

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