The team of Zhu Xuan/Chen Fuhe/Yuan Guoyong of the University of Hong Kong revealed that the replicative ability and pathogenicity of Omicron mutants are reduced Nature

Image source: Source from Pixabay University of Hong Kong On November 26, 2021, the World Health Organization officially announced a new coronavirus variant that is causing widespread epidemics as the fifth "variant of concern" (VOC) in the world, and named it Ormi Chron variant (Omicron)
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According to the latest scientific evidence, due to multiple site mutations carried on the spike protein, the Omicron strain is highly infectious and has high immune evasion properties, which significantly reduces the protective power of vaccination and the efficacy of therapeutic neutralizing antibodies
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However, little is known about the ability of this variant to replicate in cells and its pathogenicity in vivo
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On January 21, 2022, the research team of Zhu Xuan/Yuan Guoyong of the University of Hong Kong published an article entitled "Attenuated replication and pathogenicity of SARS-CoV-2 B.
1.
1.
529 Omicron" online in the journal Nature (Shuai Huiping of the University of Hong Kong).
Dr.
Chen Fuhe, Hu Bingjie, Chai Yue, Yuan Zitai and Dr.
Yin Feifei from Hainan Medical College are co-first authors)
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The study found that compared to the wild-type strain and other variants of concern that have caused epidemics before, the Omicron variant has a significantly reduced ability to replicate in human lung and intestinal epithelial cells
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Infectious animal models established in human ACE2 transgenic mice further confirmed that the Omicron variant is less fertile and less pathogenic
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The team first found by infecting human lung epithelial (Calu3) and human intestinal epithelial (Caco2) cells with Omicron and Omicron (R346K) variants, their replication ability and the pathogenicity of causing cytopathic changes were compared with wild type.
SARS-CoV-2 was significantly attenuated, while variant strains of concern, including Alpha, Beta, and Delta strains, showed comparable or even slightly enhanced replication ability to wild-type strains
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Interestingly, the difference in the replication ability of Omicron and the wild-type strain narrowed in monkey kidney cells (VeroE6)
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Since the main way that 2019-nCoV invades human lung and intestinal epithelium is cell membrane protein transmembrane serine protease 2 (TMPRSS2)-dependent cell membrane fusion, monkey kidney epithelial cells lack TMPRSS2 and cannot effectively mediate the viral invasion of cell membrane fusion
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Therefore, the team further speculated that the difference in the replication ability of Omicron in different cell lines may be related to the fact that the virus's spike protein carries multiple mutations located at the protease cleavage site, and its ability to utilize the membrane protease TMPRSS2 is reduced, affecting The ability of the virus to invade and thus reduce its ability to replicate
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Pseudovirus experiments confirmed that compared with wild-type strains and other concerned variants, the ability of Omicron to utilize TMPRSS2 was generally reduced by 6.
6-47.
4 times, and the sensitivity to TMPRSS2 inhibitors was significantly reduced
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Similarly, the infectivity experiments also came to the same conclusion as the pseudovirus experiments, verifying that the reduced replication ability of Omicron in host cells where the virus relies on TMPRSS2 protease for invasion is directly related to the reduced ability of the spike protein to be cleaved by TMPRSS2.
related assumptions
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The team then used K18-hACE2 transgenic mice to further study the replication ability of Omicron in vivo and its pathogenicity to the body
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Infectious animal models confirmed the cellular-level findings, showing that Omicron has significantly reduced replication capacity compared to wild-type and other variants of interest in mouse nasal epithelium as well as in lung epithelium
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More importantly, Omicron infection induced weaker pathological changes in lung tissue and was less lethal in infected mice
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Overall, this study provides important scientific evidence for the infectivity and pathogenicity of the Omicron variant from a virological perspective, and lays a solid foundation for formulating public health policies and controlling virus infection and transmission
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Combined with the existing scientific evidence, the current global vaccination strategy has forced SARS-CoV-2 to enter a new evolutionary trajectory, in order to reduce the replication fitness of the virus itself in exchange for a better immune escape ability in the immune host
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The current vaccination strategy, including booster vaccination, may further induce mutation and weakening of the virus, so strengthening the monitoring of mutant strains has important public health implications
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Paper Information [Title] Attenuated replication and pathogenicity of SARS-CoV-2 B.
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529 Omicron [Author] Huiping Shuai, Jasper Fuk-Woo Chan, Bingjie Hu, Yue Chai, Terrence Tsz-Tai Yuen, Feifei Yin, Xiner Huang , Chaemin Yoon, Jing-Chu Hu, Huan Liu, Jialu Shi, Yuanchen Liu, Tianrenzheng Zhu, Jinjin Zhang, Yuxin Hou, Yixin Wang, Lu Lu, Jian-Piao Cai, Anna Jinxia Zhang, Jie Zhou, Shuofeng Yuan, Melinda A .
Brindley, Bao-Zhong Zhang, Jian-Dong Huang, Kelvin Kai-Wang To, Kwok-Yung Yuen & Hin Chu [Journal] Nature [Time] January 21, 2022 [DOI] https://doi.
org/10.
1038/ s41586-022-04442-5【Abstract】SARS-CoV-2 Omicron emerged in November 2021 and is rapidly spreading among the human population.
While recent reports reveal that the Omicron variant robustly escapes from vaccine and therapeutic neutralization antibodies, the pathogenicity of the virus remains unknown.
Here we show that the replication of the Omicron variant is dramatically attenuated in Calu3 and Caco2 cells.
Further mechanistic investigations reveal that the Omicron variant is inefficient in transmembrane serine protease 2 (TMPRSS2) usage in comparison to that of WT and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells.
Omicron replication is markedly attenuated in both the upper and lower respiratory tract of infected K18-hACE2 mice in comparison to that of WT and Delta variant, which results in its dramatically ameliorated lung pathology.
When compared with SARS-CoV-2 WT, Alpha, Beta, and Delta variant, infection by the Omicron variant causes the least body weight loss and mortality rate.
Overall,our study demonstrates that the Omicron variant is attenuated in virus replication and pathogenicity in mice in comparison with WT and previous variants.
【Link】https:// This paper is by the research team Authorized to publish on the WeChat public account "Scientific Research Circle"
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