Core-like Particles of an Enveloped Animal Virus Can Self-Assemble Efficiently on Artificial Templates

Abstract

Alphaviruses are animal viruses holding great promise for biomedical applications as drug delivery vectors, functional imaging probes, and nanoparticle delivery vesicles because of their efficient in vitro self-assembly properties. However, due to their complex structure, with a protein capsid encapsulating the genome and an outer membrane composed of lipids and glycoproteins, the in-vitro self-assembly of viruslike particles, which have the functional virus coat but carry an artificial cargo, can be challenging. Fabrication of such alphavirus-like particles is likely to require a two-step process: first, the assembly of a capsid structure around an artificial core, second the addition of the membrane layer. Here we report progress made on the first step: the efficient self-assembly of the alphavirus capsid around a functionalized nanoparticle core.

Natural supramolecular building blocks: from virus coat proteins to viral nanoparticles

“…Another self-assembly of VLPs cooperating with nucleic acids was found in an enveloped animal virus called alphavirus. 72 Unlike other examples, it has been shown that both nonspecific and specific interactions were critical for the formation of alphavirus VLPs. 72 In addition to the presence of a 48-mer ssDNA, the charge neutralization was also required to drive AuNPs-VCPs assembly.…”

“…72 Unlike other examples, it has been shown that both nonspecific and specific interactions were critical for the formation of alphavirus VLPs. 72 In addition to the presence of a 48-mer ssDNA, the charge neutralization was also required to drive AuNPs-VCPs assembly. This phenomenon indicated that nucleoprotein precursors must form prior to the VCPs' self-assembly, which actually is a general mechanism for the in vivo self-assembly of most viruses in a native environment.…”

Modeling Viral Capsid Assembly

“…Namely, experiments have been performed in which capsid proteins assemble into icosahedral capsids around various cargoes including genomic or non-genomic RNA (e.g. [18–20, 43, 114, 115, 121, 142, 149, 264]), synthetic polyelectrolytes [20, 37, 38, 60, 114, 117, 147, 171, 232], charge-functionalized nanoparticles [68, 97, 122, 163, 164, 241, 251], DNA micelles [151] and nano-emulsions [49]. However, as discussed further below features specific to biological RNA molecules such as their tertiary structure and sequence-specific interactions likely promote selective assembly around the viral genome or help direct assembly toward particular morphologies.…”

Synthetic and Bioinspired Cage Nanoparticles for Drug Delivery

“…For example, various nanoparticles, such as quantum dots or gold nanoparticles, have been entrapped into brome mosaic virus [26,27], red clover necrotic mosaic virus (RCNMV) [28], mammalian simian virus 40 [29], and alphavirus [30]. These viral platforms were intended to be used as imaging probes.…”