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Originally Posted by https://www.science.org/content/article/nih-says-grantee-failed-report-experiment-wuhan-created-bat-virus-made-mice-sicker
In a “limited experiment,” mice infected with one of these chimeras, SHC014 WIV1, “became sicker than those infected with the WIV1 bat coronavirus. As sometimes occurs in science, this was an unexpected result … as opposed to something that the researchers set out to do,” states the letter from NIH Principal Deputy Director Lawrence Tabak.
Before the chimera work was funded, NIH had determined it was not GOF research involving what NIH calls “enhanced pathogens of pandemic potential,” because neither the new bat coronaviruses nor WIV1 were known to infect humans, the letter says. But the letter says the terms of the grant stated that if the virus experiments produced certain results, such as “a one log increase in [virus] growth,” EcoHealth should inform NIH “immediately” and that NIH would do a “secondary review” of the research, to see whether it should be re-evaluated or new biosafety measures imposed.
But “Ecohealth failed to report this finding right away, as was required by the terms of the grant,” the letter states. It says EcoHealth now has 5 days to submit all unpublished data from the project.
What I consider to be "source" material isn't a web based news compiler- it's the actual Ecohealth summary submitted to NIH.
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3.1 In vivo infection of Human ACE2 (hACE2) expressing mice with SARSr-CoV S protein
variants
In Year 5, we continued with in vivo infection experiments of diverse bat SARSr-CoVs on
transgenic mice expressing human ACE2. Mice were infected with 4 strains of SARSr-CoVs
with different S protein, including the full-length recombinant virus of SARSr-CoV WIV1 and
three chimeric viruses with the backbone of WIV1 and S proteins of SHC014, WIV16 and
Rs4231, respectively. Pathogenicity of the 4 SARSr-CoVs was evaluated by recording the
survival rate of challenged mice in a 2-week course. All of the 4 SARSr-CoVs caused lethal
infection in hACE2 transgenic mice, but the mortality rate vary among 4 groups of infected mice
(Fig. 13a). 14 days post infection, 5 out of 7 mice infected with WIV1 remained alive (71.4%),
while only 2 of 8 mice infected with rWIV1-SHC014 S survived (25%). The survival rate of mice
infected with rWIV1-WIV16S and rWIV1-4231S were 50%. Viral replication was confirmed by
quantitative PCR in spleen, lung, intestine and brain of infected mice. In brain, rWIV1, rWIV1-
WIV16S and rWIV1-4231S cannot be detected 2 days or 4 days post infection. However,
rWIV1-SHC014 was detected at all time points and showed an increasing viral titer after
infection. The viral load reached more than 10e9 genome copies/g at the dead point (Fig. 13b).
We also conducted histopathological section examination in infected mice. Tissue lesion and
lymphocytes infiltration can be observed in lung, which is more significant in mice infected with
rWIV1-SHC014 S (Fig. 13d) than those infected with rWIV1 (Fig. 13c). These results suggest
that the pathogenicity of SHC014 is higher than other tested bat SARSr-CoVs in transgenic
mice that express hACE2.
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I.1 What were the outcomes of the award?
The aims of our grant (R01AI110964) were to: 1) Analyze the risk that there could be a repeat of the SARS outbreak, due to bat coronaviruses still circulating in China; 2) Work out how we can predict which bat viruses would be most likely to emerge, so that we can prevent new outbreaks; 3) Using lab tests, find out if any of the coronaviruses still present in bat populations in China have the potential to infect people. The overall goal of this work is to help design vaccines and therapeutics against future potentially emerging viruses, work out which communities are on the frontline of a new potential outbreak, and reduce the risk of them being infected by analyzing their risk behavior. During this 5-year period of work, we made significant discoveries leading to 18 peer-reviewed scientific papers, including in some of the world’s foremost scientific journals.
Overall, our work shows that bats in China harbor a high number and diversity of coronaviruses, some closely related to SARSCoV(the virus that caused the SARS pandemic in 2003). We sampled over 16,000 individual bats and found evidence of hundreds of different SARS-related coronavirus genetic sequences. We found out that bats across China harbor these viruses, and that they are common, with 6.7% of bats sampled being positive. Many of these bats are found across China, Southeast Asia, South Asia and beyond, suggesting viruses with zoonotic potential may exist in those regions also. Many of these bats are abundant, and roost and feed close to people and livestock, suggesting high potential for future viral spillover. We also identified one cave system in Yunnan Province with horseshoe bats that had diverse SARSr-CoVs, including some with S proteins able to use human ACE2 as entry receptors. Bats in this cave carried SARSr-CoVs with all unique genetic elements of the SARS-CoV outbreak virus, suggesting that this site may be a potential public health risk.
To analyze which viruses were a potential public health risk, we managed to culture three strains of SARSr-CoVs from bat feces: WIV1, WIV16 and Rs4874. We used the genetic codes of some of the other viruses we found in bats and inserted the spike protein genes of those viruses (the proteins that attach to cells) into the cultured viruses. By doing this experiment we showed that other viruses may also be able to infect human cells, and were able to do this safely without the need to culture large amounts of virus. We also showed that some of these viruses cause SARS-like illness in mice that are adapted to have similar cell surface receptors to people. This work proves that there is a clear and present danger for future emergence of novel SARS-like viruses in people.
We also demonstrated that outbreaks can happen in livestock. In 2016-17, we analyzed fecal samples from pigs at 5 farms in South China affected by a fatal diarrheal disease. We discovered a new coronavirus, Swine Acute Diarrheal Syndrome coronavirus (SADS-CoV), and showed that it originates in bats, caused the death of more than 20,000 pigs, but also is able to infect human cells in the lab.
Our work has produced predictive algorithms to map hotspots of viral risk so that public health measures can be taken to protect communities at the frontline of potentially the next SARS pandemic. We have produced new reagents and viral cultures that can be used by labs across the world to design novel vaccines and therapeutics against SARS-CoV and other related viruses that might emerge in the future. Finally, our work has been used directly by the WHO to list SARS-related coronaviruses as one of the highest priority group of pathogens with pandemic potential, so that efforts can be taken to stop a future pandemic before it happens.
This is not gain of function as broadly defined by "one skilled in the art" as the legalese would say. This was an experiment to define the function/tropism of other naturally occuring Cov's using chimeric viruses by grafting other viral Spike proteins on a nonhuman-infectious WIV1 virus, in lieu of isolation and propagation of the other naturally occuring virus isolates. This was to help to define which of those naturally occurring bat CoV's may have the potential to spill over into humans, not to design a bat/human infecting CoV with a gain of function that enabled human infection.