SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation T9I


Basic Characteristics of Mutations
Mutation Site T9I
Mutation Site Sentence At an infection dose of 104 plaque-forming units (PFU), WA1 virus carrying Omicron BA.1 Nsp14(I42V), E(T9I), M(D3G/Q19E/A63T), but not Nsp6(Delta105-107, I189V), substitutions showed significant reduction in lethality.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region E
Standardized Encoding Gene E  
Genotype/Subtype BA.1
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 39660912
Title Combined mutations in nonstructural protein 14, envelope, and membrane proteins mitigate the neuropathogenicity of SARS-CoV-2 Omicron BA.1 in K18-hACE2 mice
Author Sangare K,Liu S,Selvaraj P,Stauft CB,Starost MF,Wang TT
Journal mSphere
Journal Info 2025 Jan 28;10(1):e0072624
Abstract We previously reported that mutations outside the spike protein play a role in the attenuation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.1 variant in human ACE2 transgenic mice (K18-hACE2). Here, we assessed the pathogenicity of SARS-CoV-2 (WA1/2020) containing mutations from the Omicron BA.1 variant in K18-hACE2 mice. At an infection dose of 10(4) plaque-forming units (PFU), WA1 virus carrying Omicron BA.1 Nsp14(I42V), E(T9I), M(D3G/Q19E/A63T), but not Nsp6(Delta105-107, I189V), substitutions showed significant reduction in lethality. Interestingly, reduction of viral load is more pronounced in the brains than in the lungs. Subsequent analyses suggest that BA.1 E(T9I) and M(D3G/Q19E/A63T) substitutions result in less efficient packaging of virus-like particles. Given that Nsp14(I42V), E(T9I), M(Q19E/A63T) are well preserved in subsequent omicron subvariants, including currently circulating variants, our findings highlight the importance of understanding how non-spike mutations affect the pathogenicity of SARS-CoV-2 variants. IMPORTANCE: 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.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.