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J R Soc Interface. 2019 Nov 29;16(160):20190411. doi: 10.1098/rsif.2019.0411. Epub 2019 Nov 6. Frustration and fidelity in influenza genome assembly.
Farheen N1, Thattai M2.
Author information
1 Indian Institute of Science Education and Research, Pune 411008, India. 2 Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.
Abstract
The genome of the influenza virus consists of eight distinct single-stranded RNA segments, each encoding proteins essential for the viral life cycle. When the virus infects a host cell, these segments must be replicated and packaged into new budding virions. The viral genome is assembled with remarkably high fidelity: experiments reveal that most virions contain precisely one copy of each of the eight RNA segments. Cell-biological studies suggest that genome assembly is mediated by specific reversible and irreversible interactions between the RNA segments and their associated proteins. However, the precise inter-segment interaction network remains unresolved. Here, we computationally predict that tree-like irreversible interaction networks guarantee high-fidelity genome assembly, while cyclic interaction networks lead to futile or frustrated off-pathway products. We test our prediction against multiple experimental datasets. We find that tree-like networks capture the nearest-neighbour statistics of RNA segments in packaged virions, as observed by electron tomography. Just eight tree-like networks (of a possible 262 144) optimally capture both the nearest-neighbour data and independently measured RNA-RNA binding and co-localization propensities. These eight do not include the previously proposed hub-and-spoke and linear networks. Rather, each predicted network combines hub-like and linear features, consistent with evolutionary models of interaction gain and loss.
KEYWORDS:
influenza; network evolution; segmented virus; self-assembly
PMID: 31690232 DOI: 10.1098/rsif.2019.0411