Modeling the effects of genome packaging on the Circovirus 3D structure

Circoviruses are the smallest pathogens able to infect mammals. In particular, Porcine CircoVirus type 2 (PCV2) causes significant damage to pig farms worldwide. The latest PCV2 structure reported on the PDB shows 60 copies of the capsid proteins (CPs) in icosahedral symmetry with one bound tetranucleotide per protein with sequence Py-Py-Pu-Pu (Py, pyrimidine; Pu, purine) [1]. Using this information, we modeled the CPs N-termini, which are resolved in the cryo-EM structure. These models were relaxed through coarse-grained molecular dynamics simulations (CGMD) using SIRAH [2]. Then, we generated different genome topologies using lattice polymer models and SPQR [3].

Notably, the virion models are highly compact, leaving void spaces to place only a few thousand water molecules. Although all models are within AFM and TEM measured sizes, CGMD simulations identify two populations with different sizes, which are consistent with different protein-DNA interaction energies. Our findings suggest that various highly compact genome arrangements are structurally possible. However, only certain topologies might be identified in terms of protein-DNA interactions.

References:

[1] Khayat R, et al. Virology 537:186-197, 2019.

[2] Klein F, et al. J. Struct. Biol. 215:107985, 2023.

[3] Poblete S et al. Nucleic Acids Res. 46:1674-1683, 2018.