Dataset Information

Efficient genome replication in influenza A virus requires NS2 and sequence beyond the canonical promoter

ABSTRACT: Influenza A virus encodes promoters in both the sense and antisense orientations. These support the generation of new genomes, antigenomes, and mRNA transcripts. Characterization of the influenza promoters using minimal replication assays—transfections with viral polymerase, nucleoprotein, and a genomic template—defined their sequence as 13nt at the 5’ end of the viral genomic RNA (U13) and 12nt at the 3’ end (U12).Other than a single position the U12 and U13 sequences are identical between all eight RNA molecules that comprise the segmented influenza genome.Nevertheless, each segment can exhibit different transcriptional dynamics despite possessing identical promoters.Minimal replication assays lack the influenza protein NS2, which can modulate transcription and replication differentially between influenza segments.This suggests that NS2 expression may redefine the influenza A virus promoter.In this work we assess how internal regions of sequence in two genomic segments, HA and PB1, may contribute to NS2-dependent replication as well as map such interactions down to individual nucleotides in PB1. We find that the expression of NS2 significantly alters sequence requirements for efficient replication beyond the identical U12 and U13 sequence, providing a mechanism for the divergent replication and transcription dynamics across the influenza A virus genome.

ORGANISM(S): Influenza A virus (A/WSN/1933(H1N1))

PROVIDER: GSE276697 | GEO | 2024/09/10

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Highly pathogenic avian influenza virus (HPAIV) is a permanent threat due to its capacity to cross species barriers and generate severe infections and high mortality in humans. Recent findings have highlighted the potential role of PB1-F2, a small accessory influenza protein, in the pathogenesis process mediated by HPAIV in mammals. In this study, using a recombinant H5N1 HPAIV (wt) and its PB1-F2-deleted mutant (M-NM-^TF2), we studied the effects of PB1-F2 in a chicken model. Unexpectedly, when using low inoculation dose we observed that the wt-infected chickens had a higher survival rate than the M-NM-^TF2-infected chickens, a feature that contrasts with what is usually observed in mammals. High inoculation dose had similar mortality rate for both viruses, and comparison of the bio-distribution of the two viruses indicated that the expression of PB1-F2 allows a better spreading of the virus within chicken embryos. Transcriptomic profiles of lungs and blood cells were characterized at two days post-infection in chickens inoculated with the wild type (wt) or the M-NM-^TF2 mutant viruses. In lungs, the expression of PB1-F2 during the infection induced pathways related to calcium signaling and repressed a large panel of immunological functions. In blood cells, PB1-F2 was associated to a gene signature specific for mitochondrial dysfunction and down-modulated leucocytes activation. Finally we compared the effect of PB1-F2 in lungs of chickens and mice. We identified that gene signature associated to tissue damages is a PB1-F2 feature shared by the two species; by contrast, the early inhibition of immune response mediated by PB1-F2 observed in chickens is not seen in mice. In summary, our data suggest that PB1-F2 expression deeply affect the immune host response in chickens in a way that may attenuate pathogenicity, a feature differing from what was previously observed in mammal species. Three-condition experiment, virus-infected (wt or M-NM-^TF2) vs. Mock-infected chickens. Biological replicates: 2x5 control replicates, 5 wt replicates, 5 M-NM-^TF2 replicates.

Dataset Information

Efficient genome replication in influenza A virus requires NS2 and sequence beyond the canonical promoter

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets