University of Massachusetts Medical School Faculty Publications

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Program in Bioinformatics and Integrative Biology

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Article Postprint


*Genome, Viral; Influenza A virus; *Models, Genetic; RNA, Viral; Thermodynamics; Virion


Bacterial Infections and Mycoses | Biophysics | Genomics | Investigative Techniques | Respiratory Tract Diseases | Virology


The genome of influenza A virus consists of eight separate RNA segments, which are selectively packaged into virions prior to virus budding. The microscopic mechanism of highly selective packaging involves molecular interactions between packaging signals in the genome segments and remains poorly understood. We propose that the condition of proper packaging can be formulated as a large gap between RNA-RNA interaction energies in the viable virion with eight unique segments and in improperly packed assemblages lacking the complete genome. We then demonstrate that selective packaging of eight unique segments into an infective influenza virion can be achieved by self-repulsion of identical segments at the virion assembly stage, rather than by previously hypothesized intricate molecular recognition of particular segments. Using Monte Carlo simulations to maximize the energy gap, without any other assumptions, we generated model eight-segment virions, which all display specific packaging, strong self-repulsion of the segments, and reassortment patterns similar to natural influenza. The model provides a biophysical foundation of influenza genome packaging and reassortment and serves as an important step towards robust sequence-driven prediction of reassortment patterns of the influenza virus.

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Accepted Manuscript posted as allowed by publisher's copyright policy

DOI of Published Version



Phys Rev Lett. 2013 Mar 1;110(9):098104. Epub 2013 Feb 28. DOI 10.1103/PhysRevLett.110.098104

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Link to Article in PubMed

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Physical review letters

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