Combined mutations in nonstructural protein 14, envelope, and membrane proteins mitigate the neuropathogenicity of SARS-CoV-2 Omicron BA.1 in K18-hACE2 mice
Inoculation of transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) with SARS-CoV-2 often leads to a fatal brain infection. Omicron BA.1 variant, however, was found to be non-lethal in this model. Here, we systematically assessed the effect of individual mutations of Omicron BA.1 on the pathogenicity of the virus in hACE2 transgenic mice and found that combination of 5 mutations of Nsp14, E, and M of BA.1 variant significantly lowered brain viral load and reduced lethality. These results provide new insights into how SARS-CoV-2 Omicron BA.1 is attenuated.
Authors
- Tony T. Wang (ORCID: https://orcid.org/0000-0001-8983-1721)
- Prabhuanand Selvaraj (ORCID: https://orcid.org/0000-0001-7266-3928)
- Charles B. Stauft (ORCID: https://orcid.org/0000-0001-5633-2950)
- Matthew F. Starost (ORCID: https://orcid.org/0000-0002-6234-4875)
- Kotou Sangare (ORCID: https://orcid.org/0000-0002-6750-820X)
- Shufeng Liu (ORCID: https://orcid.org/0000-0001-9969-6041)
Institutions
- National Institutes of Health (US)
- Center for Biologics Evaluation and Research (US)
- Office of Research Services (US)
- Food and Drug Administration (TH)
Publication Details
- Journal
- mSphere
- Published
- 2024-12-11
- DOI
- https://doi.org/10.1128/msphere.00726-24
- Citations
- 3
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- National Institutes of Health
- U.S. Food and Drug Administration
- National Institute of Allergy and Infectious Diseases