Selective viral vector transduction of ErbB4 expressing cortical interneurons in vivo with a viral receptor-ligand bridge protein

Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16703-8. doi: 10.1073/pnas.1006233107. Epub 2010 Sep 7.


Both treatment of disease and basic studies of complex tissues can benefit from directing viral vector infection to specific cell types. We have used a unique cell targeting method to direct viral vector transduction to cerebral cortical neurons expressing the neuregulin (NRG) receptor ErbB4; both NRG and ErbB4 have been implicated in schizophrenia, and ErbB4 expression in cerebral cortex is known to be restricted to inhibitory neurons. We find that a bridge protein composed of the avian viral receptor TVB fused to NRG, along with EnvB-pseudotyped virus, is able to direct infection selectively to ErbB4-expressing inhibitory cortical neurons in vivo. Interestingly, although ErbB4 is expressed in a broad range of cortical inhibitory cell types, NRG-dependent infection is restricted to a more selective subset of inhibitory cell types. These results demonstrate a tool that can be used for further studies of NRG and ErbB receptors in brain circuits and demonstrate the feasibility for further development of related bridge proteins to target gene expression to other specific cell types in complex tissues.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Base Sequence
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • DNA Primers / genetics
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Genetic Vectors*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Interneurons / metabolism*
  • Ligands
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Mice, Transgenic
  • Neuregulins / genetics
  • Neuregulins / metabolism
  • Rabies virus / genetics
  • Rats
  • Receptor, ErbB-4
  • Receptors, Virus / genetics
  • Receptors, Virus / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transduction, Genetic*


  • Avian Proteins
  • DNA Primers
  • Ligands
  • Neuregulins
  • Receptors, Virus
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • ErbB Receptors
  • Erbb4 protein, mouse
  • Erbb4 protein, rat
  • Receptor, ErbB-4