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Host factor Rab11a is critical for efficient assembly of influenza A virus genomic segments
Journal article   Open access   Peer reviewed

Host factor Rab11a is critical for efficient assembly of influenza A virus genomic segments

Julianna Han, Ketaki Ganti, Veeresh Kumar Sali, Carly Twigg, Yifeng Zhang, Senthamizharasi Manivasagam, Chieh-Yu Liang, Olivia A Vogel, Iris Huang, Shanan N Emmanuel, …
PLoS pathogens, Vol.17(5), pp.e1009517-e1009517
05/2021
DOI: 10.1371/journal.ppat.1009517
PMCID: PMC8136845
PMID: 33970958
url
https://doi.org/10.1371/journal.ppat.1009517View
Published (Version of record) Open Access

Abstract

It is well documented that influenza A viruses selectively package 8 distinct viral ribonucleoprotein complexes (vRNPs) into each virion; however, the role of host factors in genome assembly is not completely understood. To evaluate the significance of cellular factors in genome assembly, we generated a reporter virus carrying a tetracysteine tag in the NP gene (NP-Tc virus) and assessed the dynamics of vRNP localization with cellular components by fluorescence microscopy. At early time points, vRNP complexes were preferentially exported to the MTOC; subsequently, vRNPs associated on vesicles positive for cellular factor Rab11a and formed distinct vRNP bundles that trafficked to the plasma membrane on microtubule networks. In Rab11a deficient cells, however, vRNP bundles were smaller in the cytoplasm with less co-localization between different vRNP segments. Furthermore, Rab11a deficiency increased the production of non-infectious particles with higher RNA copy number to PFU ratios, indicative of defects in specific genome assembly. These results indicate that Rab11a+ vesicles serve as hubs for the congregation of vRNP complexes and enable specific genome assembly through vRNP:vRNP interactions, revealing the importance of Rab11a as a critical host factor for influenza A virus genome assembly.
A549 Cells Genome, Viral HEK293 Cells Humans Influenza A virus - genetics Influenza A virus - isolation & purification Influenza, Human - genetics Influenza, Human - virology rab GTP-Binding Proteins - genetics rab GTP-Binding Proteins - metabolism Ribonucleoproteins - genetics Ribonucleoproteins - metabolism Viral Proteins - genetics Viral Proteins - metabolism Virus Assembly Virus Replication

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