Controlled Integration of Polymers into Viral Capsids

In this paper, we describe the controlled incorporation of two synthetic polymers with different structures in the cowpca chlorotic mottle virus (CCMV) capsid, Poly(ethylene glycol) (PEG) chains have been attached to the amine groups of lysine residues on the outer surface of the viral capsid. The functionalization of CCMV with PEG chains provoked a slow but irreversible dissociation of the virus into PEG-coat protein (CP) subunits, likely due to steric interference between the protein-protein subunits as a result of the presence of the PEG chains. This thermodynamic instability, however, can be overcome if a second polymer, such as polystyrene sulfonate (PSS), is present within the capsid. After complete disassembly of the PEG-CCMV conjugates and removal of the viral RNA, incubation of the PEG-functionalized coat proteins with PSS resulted in the formation of much more robust PSS-CCMV-PEG capsids with a diameter of 18 nm (T = 1 capsids). These are the first virus-like particles hearing synthetic organic polymers both inside and outside the viral capsid, opening a new route to the synthesis of biohybrid nanostructured materials based on viruses.