Anterograde transneuronal tracing and genetic control with engineered yellow fever vaccine YFV-17D

Elizabeth Li, Jun Guo, So Jung Oh, Yi Luo, Heankel Cantu Oliveros, Wenqin Du, Rachel Arano, Yerim Kim, Yuh Tarng Chen, Jennifer Eitson, Da Ting Lin, Ying Li, Todd Roberts, John W. Schoggins, Wei Xu

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Transneuronal viruses are powerful tools for tracing neuronal circuits or delivering genes to specific neurons in the brain. While there are multiple retrograde viruses, few anterograde viruses are available. Further, available anterograde viruses often have limitations such as retrograde transport, high neuronal toxicity or weak signals. We developed an anterograde viral system based on a live attenuated vaccine for yellow fever—YFV-17D. Replication- or packaging-deficient mutants of YFV-17D can be reconstituted in the brain, leading to efficient synapse-specific and anterograde-only transneuronal spreading, which can be controlled to achieve either monosynaptic or polysynaptic tracing. Moreover, inducible transient replication of YFV-17D mutant is sufficient to induce permanent transneuronal genetic modifications without causing neuronal toxicity. The engineered YFV-17D systems can be used to express fluorescent markers, sensors or effectors in downstream neurons, thus providing versatile tools for mapping and functionally controlling neuronal circuits.

Original languageEnglish (US)
Pages (from-to)1542-1551
Number of pages10
JournalNature methods
Volume18
Issue number12
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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