Alphaviruses: Semliki Forest virus and Sindbis virus vectors for gene transfer into neurons

Alphaviral vectors based on Semliki Forest virus and Sindbis virus infect many host cell types, causing rapid and high-level transgene expression. Compared to other viruses used to infect CNS cell and tissue preparations, Semliki Forest virus and Sindbis virus exhibit an outstanding preference for neurons rather than glial cells. High-titer vector generation typically requires biosafety level 1 or 2 containment and occurs in less than 2 days. Wild-type vectors are cytotoxic, permitting short-term transgene expression. However, mutant vectors with decreased cytotoxicity, to prolong host cell survival, have been developed. They also increase transgene expression and cellular coinfection, permitting heteromeric protein expression in individual cells. Other mutants with temperature-dependent control of transgene expression and altered host cell preference to target interneurons and astrocytes rather than principal neurons are available. Because of these advantages, alphaviral vectors are increasingly used in neurobiological and other studies, including structural biology, vaccine development, and cancer treatment.