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måndag 20 mars 2023

Ihmisen anti(retro)virusjärjestelmä APOBEC voi avustaa virusta mutatoitumisessa ja täten evoluutiossa.

Selvitystä  APOBEC- systeemistä  on  tämän päivän GITHUB-aiheissa:

Linkissä  esitetyssä variantissa on epätavallinen tryptofaaniks i(W)  muuntuminen. Sitä harvoin tapaa  näissä sars-2-koronavirusvarianteissa mutatoituneena.   Isäntäkehon APOBEC-järjestelmän ominaisuudet ja tiettyjen nukleotidikombinaatioitten prioritointi ennen ja jälkeen mutaatiokohdan vaikuttaa sen mahdollisuuksiin olla antiviraali.  Tässä kuitenkin ilmenee se  kombinaatio, mikä on epäsuotuinen APOBEC:ille.     ( Pohtimista).

https://github.com/cov-lineages/pango-designation/issues/1776

XBB.2.3 Sublineage with S:G184V, ORF1a:R2159W #1776

Evidence
This lineage only very recently appeared and appears to be growing quickly. It seems to have originated in India and subsequently spread to Singapore and the US. Singapore uploads sequences faster than anyone, so I think this likely has spread elsewhere in Asia and will start to show up in sequences in the coming weeks.
Mutations from S:180 to S:186 have been ubiquitous in recent months, so it seems likely they confer a very modest increase in antibody evasion.

ORF1a:R2159W is more interesting. Overall, it has been a rare mutation throughout the pandemic. It was in an undesignated B.1 saltation lineage that rose to about 5% prevalence in Canada in late 2020/early 2021, and it was also in DN.1 (BQ.1.1.5 + S:K147N) and DN.1.1 (DN.1 + S:Y453F, ORF1a:V721I, ORF1a:N2752S).

 It involves a C->T mutation, which is easily the most common type.

 https://user-images.githubusercontent.com/33738461/226120549-154c4d86-49e1-4e25-ba8f-15f6f586d99b.png

 'However, C->T mutation frequency is mostly driven by APOBEC, and the nucleotide context at C6740 (CA upstream and GG downstream) is unfavorable for APOBEC, which prefers A or T in the two closest upstream & downstream nucleotides.

 

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