Nucleotide sequence as key determinant driving insertions at influenza A virus hemagglutinin cleavage sites

Spronken, Monique I.; Funk, Mathis; Gultyaev, Alexander P.; Bruin, Anja C. M.; Fouchier, Ron A. M.; Richard, Mathilde

doi:10.1038/s44298-024-00029-1

Nucleotide sequence as key determinant driving insertions at influenza A virus hemagglutinin cleavage sites

detalle del documento

IDENTIFICACIÓN

doi:10.1038/s44298-024-00029-1...

Autor

Spronken, Monique I. Funk, Mathis Gultyaev, Alexander P. Bruin, Anja C. M. Fouchier, Ron A. M. Richard, Mathilde

Langue

Editor

Nature

Categoría

Epidemiology

Año

2024

fecha de cotización

15/5/2024

Palabras clave

viruses influenza indels h5 nucleotide

Métrico

Resumen

Highly pathogenic avian influenza viruses (HPAIVs) emerge from H5 and H7 low pathogenic avian influenza viruses (LPAIVs), most frequently upon insertions of nucleotides coding for basic amino acids at the cleavage site (CS) of the hemagglutinin (HA).

The exact molecular mechanism(s) underlying this genetic change and reasons underlying the restriction to H5 and H7 viruses remain unknown.

Here, we developed a novel experimental system based on frame repair through insertions or deletions (indels) of HAs with single nucleotide deletions.

Indels were readily detected in a consensus H5 LPAIV CS at low frequency, which was increased upon the introduction of only one substitution leading to a longer stretch of adenines at the CS.

In contrast, we only detected indels in H6 when multiple nucleotide substitutions were introduced.

These data show that nucleotide sequence is a key determinant of insertions in the HA CS, and reveal novel insights about the subtype-specificity of HPAIV emergence.

Spronken, Monique I.,Funk, Mathis,Gultyaev, Alexander P.,Bruin, Anja C. M.,Fouchier, Ron A. M.,Richard, Mathilde, 2024, Nucleotide sequence as key determinant driving insertions at influenza A virus hemagglutinin cleavage sites, Nature