University of Massachusetts Medical School Faculty Publications

Title

Segment self-repulsion is the major driving force of influenza genome packaging

UMMS Affiliation

Program in Bioinformatics and Integrative Biology

Publication Date

3-1-2013

Document Type

Article

Subjects

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

Disciplines

Biophysics | Genomics | Virology

Abstract

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.

Rights and Permissions

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

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Physical review letters

PubMed ID

23496749