A Viral Receptor Complementation Strategy to Overcome CAV-2 Tropism for Efficient Retrograde Targeting of Neurons

Shu Jing Li, Alexander Vaughan, James Fitzhugh Sturgill, Adam Kepecs

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Retrogradely transported neurotropic viruses enable genetic access to neurons based on their long-range projections and have become indispensable tools for linking neural connectivity with function. A major limitation of viral techniques is that they rely on cell-type-specific molecules for uptake and transport. Consequently, viruses fail to infect variable subsets of neurons depending on the complement of surface receptors expressed (viral tropism). We report a receptor complementation strategy to overcome this by potentiating neurons for the infection of the virus of interest—in this case, canine adenovirus type-2 (CAV-2). We designed AAV vectors for expressing the coxsackievirus and adenovirus receptor (CAR) throughout candidate projection neurons. CAR expression greatly increased retrograde-labeling rates, which we demonstrate for several long-range projections, including some resistant to other retrograde-labeling techniques. Our results demonstrate a receptor complementation strategy to abrogate endogenous viral tropism and thereby facilitate efficient retrograde targeting for functional analysis of neural circuits. Retrograde viruses are indispensable tools for linking neural connectivity with function; however, their use is often limited by poor or variable infectivity. Li et al. report a viral receptor complementation strategy for more efficient and tropism-free projection-specific neuronal targeting.

Original languageEnglish
Pages (from-to)905-917.e5
JournalNeuron
Volume98
Issue number5
DOIs
StatePublished - Jun 6 2018

Keywords

  • CAR
  • CAV-2
  • complementation
  • labeling
  • pathway
  • projection
  • retrograde
  • targeting
  • tropism
  • virus

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