Figure 1. Structure of vaccinia virus (PMID:15249657)

Vaccinia virus (VACV or VV) is a large, enveloped, double-stranded linear DNA virus with a complex structure. It has a length of approximately 190 kb and encodes about 200 genes. The viral particle is brick-shaped, with dimensions of approximately 300x240x120 nm. VV has a broad host range and a large capacity for inserting exogenous genes. It replicates and proliferates in the cytoplasm of cells without integrating into the host cell genome.

Oncolytic vaccinia viruses (oVVs) exhibit a natural tropism for tumors. To further enhance their targeting and specificity, researchers have modified them. The two main modification strategies are:

1) Deletion of vaccinia growth factor (VGF)

2) Deletion of thymidine kinase (TK)

The VGF gene in VV is homologous to epidermal growth factor (EGF) and can bind to the EGF receptor (EGFR) on the cell surface. This activates the Ras pathway, further initiating the cell cycle and promoting cell differentiation. Cell differentiation, in turn, promotes TK synthesis, increasing viral infection efficiency. This is crucial for viral expansion in normal cells but is not essential in tumor cells that can proliferate extensively.

Among the various VV strains, Western Reverse (WR), Lister, Wyeth, and Copenhagen strains exhibit oncolytic properties, with Western Reverse demonstrating the strongest oncolytic activity.