Pseudovirus was first discovered from a particle that had been produced from cultured mouse cells that were infected by polyomavirus. Researchers identified fragments of mouse DNA encapsulated within the polyomavirus protein coat upon further analysis. Pseudoviruses can be produced either naturally during an infection or artificially in a laboratory for research purposes. They contain host-cell DNA fragments without any of the nucleic acid components of the infectious virus to which they are connected.

The modified pseudovirus genetic material inhibits these particles from developing viral surface proteins of their own, unless the pseudovirus has connection to an additional plasmid or stable cell line that expresses these proteins. Pseudoviruses can replicate only once after penetrating susceptible cells, which is similar to wild-type (WT) viruses that often replicate multiple times. These viruses are much safer to handle than the virus from which they originated although the conformational structure of the surface proteins of pseudoviruses closely resembles that of the native virus.

The several advantages associated with the pseudovirus include that they can be developed easily, vaccine evaluation, pathways of virus inhibition, and mechanisms of cellular tropism.

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