Pseudotype

Pseudotype refers to a virus particle whose outer envelope proteins are derived from a different virus than its genome. The genome donor determines replication properties, while the envelope donor determines cell entry tropism by binding to specific receptors. Pseudotyping is achieved by producing virions that package the genome of interest inside a heterologous envelope, often using packaging systems in which the envelope proteins are supplied in trans. The resulting pseudotyped particles can enter cells through the entry pathway of the envelope donor, enabling exploration of receptor usage and enabling gene delivery even to cell types that would be poorly transduced by the native virus.

Applications: In virology and gene therapy, pseudotyping is used to retarget viral vectors, to study entry mechanisms, and to improve safety profiles. Lentiviral vectors are commonly pseudotyped with VSV-G to achieve broad tropism and stability, while envelopes such as RD114, MLV, or influenza HA can confer different host ranges. Pseudotyped vectors are typically replication-incompetent and used in controlled settings to deliver reporter genes or therapeutic payloads, or to perform neutralization and antibody-escape studies.

Limitations: Compatibility between genome and envelope affects titer and infectivity; pseudotyping does not eliminate all biosafety concerns and regulatory requirements remain. Some envelope proteins may be unstable or cause cytotoxicity; tissue-specific tropism may still limit utility.

See also: viral vector, pseudotyping, gene therapy, viral entry.