Generating enveloped virus-like particles with in vitro assembled cores

Alphaviruses are comprised of a nucleocapsid core surrounded by a lipid membrane containing glycoprotein spikes. Previous work demonstrated that in vitro assembled core-like particles are similar in structure to the nucleocapsid core in the native virus. Here we demonstrate that in vitro assembled core-like particles can be inserted into viral glycoprotein-expressing cells to generate enveloped virus-like particles. These virus-like particles bud from cells like native virus, are similar in size to the native virus, and can enter cells to release the contents of the core-like particle into the cytoplasm of the cell. Virus-like particles can be used to infect cells with biological and non-biological cargoes. The generation of enveloped virus-like particles containing an in vitro core and in vivo synthesized glycoproteins has applications for gene and drug delivery, medical imaging, and also basic mechanistic studies of virus assembly.