Published May 10, 2021 | Version v1
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Host factor Rab11a is critical for efficient assembly of influenza A virus genomic segments

Description

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.

Data availability

All relevant data are within the manuscript and its Supporting Information files.

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Additional details

Identifiers

DOI
10.1371/journal.ppat.1009517
Other
oai:uchicago.tind.io:6055

Funding

National Institutes of Health
Molecular and Cellular Biology training program at The University of Chicago
National Institutes of Health
Diversity Supplement
NIAID
R01AI125268
CEIRS
HHSN272201400004C
NIAID
R01AI123359
NIAID
R01AI127775

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Microbiology