songlihua January 17, 2024 6:39pm
Thank ScienceCast Board for this opportunity! I appreciate it. This preprint paper is being misinterpreted on social media. I would like to state several facts:
1. The GX_P2V virus has been published in Nature in 2020 (doi: 10.1038/s41586-020-2169-0). It is not a brand-new virus.
2. The GX_P2V(short_3UTR) mutant was published in Emerging Microbes & Infections in 2022 (doi: 10.1080/22221751.2022.2151383). This cell-adapted mutant is the actual isolate published in the Nature paper. So, the original GX_P2V virus was not isolated. Clearly the original GX_P2V virus in the pangolin sample has severe growth deficiency in Vero cells.
3. The GX_P2V virus is not a human pathogen, although, based on molecular and animal infection experiments, it can infect a broad spectrum of host species, like human, cat, pig, golden hamster, mouse, rat et al. There is no evidence of the original GX_P2V virus circulating in these animals, not even consider this GX_P2V(short-3UTR) mutant. Please refer to publications: EMBO J, doi: 10.15252/embj.2021109962 and J Virol, doi: 10.1128/jvi.01719-22.
4. The GX_P2V(short_3UTR) isolate is highly attenuated in in vitro and in vivo models. In Vero, BGM, and Calu-3 cell lines, the virus induced only mild cytopathic effects, notably failing to produce viral plaques even on the human lung cell line Calu-3. In golden hamster and BALB/c mouse models, the virus can infect the animals' respiratory tracts but did not result in any observable disease symptoms. The attenuated nature of GX_P2V(short_3UTR) was also validated in two distinct human ACE2-transgenic mouse models. Please refer to publications: Emerging Microbes & Infections, doi: 10.1080/22221751.2022.2151383 and J Virol, doi: 10.1128/jvi.01719-22.
The attenuation of GX_P2V(short_3UTR) was also hinted in the Nature paper on the GX_P2V(short_3UTR) isolate (doi: 10.1038/s41586-020-2169-0). In Extended Data Figure 1, after infecting Vero cells for five days, GX_P2V caused noticeable cytopathic effects, but which were limited to cell rounding and mild cytolysis, which starkly contrasted with the severe cytopathic effects reported in SARS-CoV-2.
5. The public has developed a high level of population immunity against GX_P2V due to SARS-CoV-2 immunizations and infections. Collectively, the biological safety risk posed by GX_P2V(short_3UTR) is extremely low. I don’t think there is any immediate risk of spillover into the human population. Please refer to publication: J Med Virol, doi: 10.1002/jmv.29031.
6. Based on previous reports on ACE2 humanized mouse models with SARS-CoV-1 and SARS-CoV-2, there is significant variability in the outcomes of infection in these models, a topic extensively documented in the literature. A single ACE2 humanized mouse model does not constitute a reliable paradigm for evaluating viral pathogenicity. While GX_P2V(short_3UTR) proved lethal in our mouse model, it's important to consider that it did not cause disease upon infecting two other distinct ACE2 humanized mouse strains. The findings reported in this paper do not alter the fundamental nature of GX_P2V(short_3UTR) as being highly attenuated.
7. Several other research groups have repeatedly reported the spillover risk of this virus based on its spike protein binding to human ACE2. Those reports have not caught much attention. In our study, using a unique lethal model, we inadvertently reinforced the perception that this virus has a strong tropism for human brains and causes 100% mortality. We need to revise this in the subsequent revision of the paper and provide additional clarification on the intrinsic attenuated nature of the virus.
8. The GX_P2V(short_3UTR) mutant is a promising live attenuated vaccine against pan-SARS-CoV-2. Partial results can be found in this preprint paper: https://www.researchsquare.com/article/rs-3371123/v1.