This paper describes the trafficking and functions of influenza A virus (IAV) viral ribonucleoproteins (vRNPs), which contain the genetic material of IAV, within the host cell. We emphasize how vRNPs interact with, and depend on, host factors and pathways, how vRNP structure contributes to its function and the key open questions that still need to be answered.
The structure of vRNPs in their native form is described.
The mechanism of vRNP nuclear import is explained, including a discussion of how vRNP components interact with the cellular importin-α–importin-β1 nuclear import pathway.
Primary genome transcription and genome replication is described, focusing on how host factors contribute to these processes.
Nuclear export of vRNP, which is mediated by the cellular CRM1 (also known as exportin-1) nuclear export pathway, is illustrated.
Recent work implicating the cellular RAB11 vesicle transport system and microtubules in vRNP cytoplasmic transport in late-stage infection is described.
We highlight important open questions and suggest methods that could be used to address these gaps in our knowledge.
Influenza A viral ribonucleoprotein (vRNP) complexes comprise the eight genomic negative-sense RNAs, each of which is bound to multiple copies of the vRNP and a trimeric viral polymerase complex. The influenza virus life cycle centres on the vRNPs, which in turn rely on host cellular processes to carry out functions that are necessary for the successful completion of the virus life cycle. In this Review, we discuss our current knowledge about vRNP trafficking within host cells and the function of these complexes in the context of the virus life cycle, highlighting how structure contributes to function and the crucial interactions with host cell pathways, as well as on the information gaps that remain. An improved understanding of how vRNPs use host cell pathways is essential to identify mechanisms of virus pathogenicity, host adaptation and, ultimately, new targets for antiviral intervention.
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The authors are grateful to S. Watson for scientific editing of the manuscript. This work was supported by grants-in-aid from the Ministry of Health, Labour, and Welfare, Japan, by ERATO (Japan Science and Technology Agency) and by National Institute of Allergy and Infectious Diseases Public Health Service research grants.
The authors declare no competing financial interests.
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Eisfeld, A., Neumann, G. & Kawaoka, Y. At the centre: influenza A virus ribonucleoproteins. Nat Rev Microbiol 13, 28–41 (2015). https://doi.org/10.1038/nrmicro3367
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