UNIT 4.22 Alphaviruses: Semliki Forest Virus and Sindbis Virus Vectors for Gene Transfer into Neurons

  1. Markus U. Ehrengruber1,
  2. Sondra Schlesinger2,
  3. Kenneth Lundstrom3

Published Online: 1 OCT 2011

DOI: 10.1002/0471142301.ns0422s57

Current Protocols in Neuroscience

Current Protocols in Neuroscience

How to Cite

Ehrengruber, M. U., Schlesinger, S. and Lundstrom, K. 2011. Alphaviruses: Semliki Forest Virus and Sindbis Virus Vectors for Gene Transfer into Neurons. Current Protocols in Neuroscience. 57:4.22:4.22.1–4.22.27.

Author Information

  1. 1

    Department of Biology, Kantonsschule Hohe Promenade, Zurich, Switzerland

  2. 2

    Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri

  3. 3

    PanTherapeutics, Lutry, Switzerland

Publication History

  1. Published Online: 1 OCT 2011
  2. Published Print: OCT 2011


Alphaviral vectors based on Semliki Forest virus and Sindbis virus infect many host cell types, causing rapid and high-level transgene expression. In the CNS, Semliki Forest virus and Sindbis virus exhibit an outstanding preference for neurons rather than glial cells, compared to other viruses. Generation of high-titer virus stocks is rapid (less than two days) and typically requires biosafety level 1 or 2 containment. 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 co-infection, permitting heteromeric protein expression in individual cells. In addition, mutants with temperature-dependent control of transgene expression and altered host cell preference to target interneurons and astrocytes rather than principal neurons are available. Other alphavirus vectors based on Venezuelan equine encephalitis and Eastern equine encephalitis virus replicons have been engineered, too. Alphavirus vectors have been successfully used not only in neuroscience, but also for other applications including drug discovery, structural biology, vaccine development, and cancer therapy. Curr. Protoc. Neurosci. 57:4.22.1-4.22.27. © 2011 by John Wiley & Sons, Inc.


  • Semliki Forest virus;
  • Sindbis virus;
  • baby hamster kidney 21 (BHK) cell;
  • hippocampal neuron;
  • in vitro transcription