Electrostatic origin of the genome packing in viruses

Abstract

Many ssRNA/ssDNA viruses bind their genome by highly basic semiflexible peptide arms of capsid proteins. Here, we show that nonspecific electrostatic interactions control both the length of the genome and genome conformations. Analysis of available experimental data shows that the genome length is linear in the net charge on the capsid peptide arms, irrespective of the actual amino acid sequence, with a proportionality coefficient of 1.61 +/- 0.03. This ratio is conserved across all ssRNA/ssDNA viruses with highly basic peptide arms, and is different from the one-to-one charge balance expected of specific binding. Genomic nucleotides are predicted to occupy a radially symmetric spherical shell detached from the viral capsid, in agreement with experimental data.

Fig. 1.

Sample structure of a virus capsid (Upper) and the calculated electrostatic potential φ, ground-state energy E₀, and nucleotide density ψ₀² (Lower). The genomic polynucleotide inside the capsid is not shown for clarity, and the actual capsid protein of the brome mosaic virus (1) was used for illustrative purposes.

Fig. 2.

Nucleotide density inside the viral capsids of “Δ31 Bac” mutant of flock house virus (A) and hepatitis B virus (B). Experimental points are based on cryoelectron microscopy density profiles of refs. and . Solid lines are best fits based on Eq. 8. Experimental points beyond main peak are believed to be an instrumental error of cryoelectron microscopy and not nucleotide density (57).

Fig. 3.

Viral genome length versus net polypeptide arm charge for the WT viruses listed in Table 1. Connected points correspond to viruses that package genomes of varying length.