Vesicular stomatitis virus: re-inventing the bullet

As our understanding of the molecular aspects of human disease increases, it is becoming possible to create designer therapeutics that are exquisitely targeted and have greater efficacy and fewer side effects. One class of targeted biological agents that has benefited from recent advances in molecular biology is designer viruses. Vesicular stomatitis virus (VSV) is normally relatively innocuous but can be engineered to target cancer cells or to stimulate immunity against diseases such as AIDS or influenza. Strains of VSV that induce or direct the production of interferon are superior to wild-type strains of the virus for inducing oncolysis. These strains might also make better vaccine vectors. In this review, some of the features that make VSV an excellent platform for the development of a range of viral therapeutics are discussed. Many viruses are being developed as clinical tools for the treatment or prevention of human disease. A relative newcomer for this application is the vesicular stomatitis virus (VSV), which has had an important role in our increasing understanding of both innate and acquired immunity, as well as virology in general. Although VSV has been used extensively as a laboratory tool for probing aspects of cellular physiology, it was only during the last decade that its potential as a therapeutic has been appreciated. VSV is a clinically important vaccine vector but, more recently, it has attracted attention as an oncolytic virus. Several naturally occurring or recombinant strains of VSV have been developed as potential therapeutic vectors (Table 1). Vaccine vectors have been engineered to express foreign viral proteins designed either to elicit a specific immune response or to be more attenuated than the wild-type protein. The oncolytic strains have been selected and designed for tumor targeting and engineered to express marker proteins or suicide genes. Historically, vaccine vectors and oncolytic viruses have been based on human DNA viruses. RNA viruses are now being considered and offer several advantages, including rapid and robust growth, which aids the production and amplification of dose. The use of animal viruses, such as VSV, also avoids the problems associated with pre-existing immunity to the therapeutic vector in the patient. Recent findings demonstrated that strains of VSV that induce or direct the expression of interferon are an important advancement in the development of RNA-virus-based therapeutics