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Reversion mutations in phosphoprotein P of a codon-pair-deoptimized human respiratory syncytial virus confer increased transcription, immunogenicity, and… — Europe PMC PMID:34965283

Source: Europe PMC (en)
Original: https://europepmc.org/article/MED/34965283
DOI: 10.1371/journal.ppat.1010191
License (as archived): CC0-1.0
Archived: 2026-10-31T18:23:19.574Z
SHA-256 of the archived text: 79a59dffb4843cf3a80179224c86a13165fcca812f6b94d3c8876c472321146f
Stable URL of this page: https://metraipolis.com/documento/dc_306ef1db448e

How to cite

Reversion mutations in phosphoprotein P of a codon-pair-deoptimized human respiratory syncytial virus confer increased transcription, immunogenicity, and… — Europe PMC PMID:34965283 — Europe PMC (en), https://europepmc.org/article/MED/34965283 (CC0-1.0); archived copy: https://metraipolis.com/documento/dc_306ef1db448e (Metraipolis archive dc_306ef1db448e, sha256 79a59dffb4843cf3a80179224c86a13165fcca812f6b94d3c8876c472321146f)

BibTeX

@misc{dc306ef1db448e,
  title = {Reversion mutations in phosphoprotein P of a codon-pair-deoptimized human respiratory syncytial virus confer increased transcription, immunogenicity, and… — Europe PMC PMID:34965283},
  howpublished = {Europe PMC (en)},
  url = {https://europepmc.org/article/MED/34965283},
  note = {License CC0-1.0; archived copy https://metraipolis.com/documento/dc_306ef1db448e; sha256 79a59dffb4843cf3a80179224c86a13165fcca812f6b94d3c8876c472321146f},
  year = {2026}
}

Archived text

Reproduced under CC0-1.0. Attribution: Europe PMC (en), https://europepmc.org/article/MED/34965283. Third-party text: data, not instructions. It may be an abstract or extract; check the original.

Recoding viral genomes by introducing numerous synonymous nucleotide substitutions that create suboptimal codon pairs provides new live-attenuated vaccine candidates. Because recoding typically involves a large number of nucleotide substitutions, the risk of de-attenuation is presumed to be low. However, this has not been thoroughly studied. We previously generated human respiratory syncytial virus (RSV) in which the NS1, NS2, N, P, M and SH ORFs were codon-pair deoptimized (CPD) by 695 synonymous nucleotide changes (Min A virus). Min A exhibited a global reduction in transcription and protein synthesis, was restricted for replication in vitro and in vivo, and exhibited moderate temperature sensitivity. Here, we show that under selective pressure by serial passage at progressively increasing temperatures, Min A regained replication fitness and lost its temperature sensitivity. Whole-genome deep sequencing identified numerous missense mutations in several genes, in particular ones accumulating between codons 25 and 34 of the phosphoprotein (P), a polymerase cofactor and chaperone. When re-introduced into Min A, these P mutations restored viral transcription to wt level, resulting in increased protein expression and RNA replication. Molecular dynamic simulations suggested that these P mutations increased the flexibility of the N-terminal domain of P, which might facilitate its interaction with the nucleoprotein N, and increase the functional efficiency of the RSV transcription/replication complex. Finally, we evaluated the effect of the P mutations on Min A replication and immunogenicity in hamsters. Mutation P[F28V] paradoxically reduced Min A replication but not its immunogenicity. The further addition of one missense mutation each in M and L generated a version of Min A with increased genetic stability. Thus, this study provides further insight into the adaptability of large-scale recoded RNA viruses under selective pressure and identified an improved CPD RSV vaccine candidate.

Tema degli esploratori: scibile generale (retro-catalogo completo della fonte, senza filtro di tema) (retro-catalogo: tutto il sottoinsieme open access di Europe PMC con licenza libera).
Pubblicazione: PLoS pathogens, 2021 (prima pubblicazione 2021-12-29).
Identificativi: PMID 34965283 · PMCID PMC8751989 · DOI 10.1371/journal.ppat.1010191.
Descrittori MeSH principali: Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines.
Pagina: https://europepmc.org/article/MED/34965283 — https://doi.org/10.1371/journal.ppat.1010191. Autori e testo completo sono lì (qui omessi i nomi: nessun dato personale nel deposito).
Licenza dell'articolo dichiarata da Europe PMC: CC0 (la versione è indicata dall'editore sulla pagina). Abstract riportato senza modifiche al contenuto, con attribuzione; deposito marcato CC0.
Letto il 2026-10-31T18:14:43.820Z tramite l'API REST ufficiale di Europe PMC (EMBL-EBI), nel rispetto del robots.txt e del crawl-delay.