SARS-CoV-2 Mutation Detail Information

Virus Mutation SARS-CoV-2 Mutation V6207I


Basic Characteristics of Mutations
Mutation Site V6207I
Mutation Site Sentence In the last viremic sample collected on Day 222, other three non-conserved aa substitutions were expressed in helicase (R5661C), exonuclease (V6207I), and orf3a (L108F).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region Exonuclease
Standardized Encoding Gene ORF1b  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease -
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information Y
Treatment -
Location Italy
Literature Information
PMID 35706980
Title Competition for dominance within replicating quasispecies during prolonged SARS-CoV-2 infection in an immunocompromised host
Author Caccuri F,Messali S,Bortolotti D,Di Silvestre D,De Palma A,Cattaneo C,Bertelli A,Zani A,Milanesi M,Giovanetti M,Campisi G,Gentili V,Bugatti A,Filippini F,Scaltriti E,Pongolini S,Tucci A,Fiorentini S,d'Ursi P,Ciccozzi M,Mauri P,Rizzo R,Caruso A
Journal Virus evolution
Journal Info 2022 May 21;8(1):veac042
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge for their capability to better adapt to the human host aimed and enhance human-to-human transmission. Mutations in spike largely contributed to adaptation. Viral persistence is a prerequisite for intra-host virus evolution, and this likely occurred in immunocompromised patients who allow intra-host long-term viral replication. The underlying mechanism leading to the emergence of variants during viral persistence in the immunocompromised host is still unknown. Here, we show the existence of an ensemble of minor mutants in the early biological samples obtained from an immunocompromised patient and their dynamic interplay with the master mutant during a persistent and productive long-term infection. In particular, after 222 days of active viral replication, the original master mutant, named MB61(0), was replaced by a minor quasispecies (MB61(222)) expressing two critical mutations in spike, namely Q493K and N501T. Isolation of the two viruses allowed us to show that MB61(222) entry into target cells occurred mainly by the fusion at the plasma membrane (PM), whereas endocytosis characterized the entry mechanism used by MB61(0). Interestingly, coinfection of two human cell lines of different origin with the SARS-CoV-2 isolates highlighted the early and dramatic predominance of MB61(222) over MB61(0) replication. This finding may be explained by a faster replicative activity of MB61(222) as compared to MB61(0) as well as by the capability of MB61(222) to induce peculiar viral RNA-sensing mechanisms leading to an increased production of interferons (IFNs) and, in particular, of IFN-induced transmembrane protein 1 (IFITM1) and IFITM2. Indeed, it has been recently shown that IFITM2 is able to restrict SARS-CoV-2 entry occurring by endocytosis. In this regard, MB61(222) may escape the antiviral activity of IFITMs by using the PM fusion pathway for entry into the target cell, whereas MB61(0) cannot escape this host antiviral response during MB61(222) coinfection, since it has endocytosis as the main pathway of entry. Altogether, our data support the evidence of quasispecies fighting for host dominance by taking benefit from the cell machinery to restrict the productive infection of competitors in the viral ensemble. This finding may explain, at least in part, the extraordinary rapid worldwide turnover of VOCs that use the PM fusion pathway to enter into target cells over the original pandemic strain.
Sequence Data EPI_ISL_2484209-EPI_ISL_2484219
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.