Alphavirus vectors: development and potential therapeutic applications

Alphaviruses are RNA enveloped viruses that are proving their value as expr ession vectors. They are particularly well-suited for this role as they are easily and quickly engineered and can be used to produce high levels of pr oteins of interest. A promising and important use is as vaccines against di sease-causing agents such as HIV. The three alphaviruses now serving as vec tors are Sindbis virus, Semliki Forest vir-us (SFV) and Venezuelan equine e ncephalitis (VEE) virus. Sindbis virus and SFV are wen-known models for stu dies in molecular and cell biology; VEE virus is a human pathogen and had r eceived some previous notoriety as a potential biological weapon. It is now becoming a potentially valuable vaccine vector. All three viruses are bein g tested as vaccines but, at present, only Sindbis virus and SFV have been considered for other uses. Sindbis virus vectors have been developed to scr een libraries for the identification of new proteins and to devise sensitiv e assays to detect viruses more difficult to grow in culture. Both Sindbis virus and SFV vectors are serving as tools for fundamental studies in biolo gy, examples include development in insects and analysis of protein functio ns in neuronal cells. In this article the replication strategy of alphaviru ses and the different ways they can be engineered to serve as expression ve ctors is described. This provides an introduction to the ways these vectors have been used and illustrates the promise these vectors offer.