Abstract
Recombinant viruses are the workhorse of modern neuroscience. Whether one would like to understand a neuron’s morphology, natural activity patterns, molecular composition, connectivity or behavioural and physiologic function, most studies begin with the injection of an engineered virus, often an adeno-associated virus or herpes simplex virus, among many other types. Recombinant viruses currently enable some combination of cell type-specific, circuit-selective, activity-dependent and spatiotemporally resolved transgene expression. Viruses are now used routinely to study the molecular and cellular functions of a gene within an identified cell type in the brain, and enable the application of optogenetics, chemogenetics, calcium imaging and related approaches. These advantageous properties of engineered viruses thus enable characterization of neuronal function at unprecedented resolution. However, each virus has specific advantages and disadvantages, which makes viral tool selection paramount for properly designing and executing experiments within the central nervous system. In the current Review, we discuss the key principles and uses of engineered viruses and highlight innovations that are needed moving forward.
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Glossary
- Marker genes
-
Genes whose cell type-specific mRNA and/or protein expression can be used to identify a cell type.
- Reporter genes
-
Genes whose expressed mRNA or protein is readily detectable and can be used to characterize another gene or gene product.
- Baltimore classification
-
A classification scheme (conceived by virologist David Baltimore) that characterizes a virus based on its nucleic acid composition, in particular how the virus ultimately synthesizes mRNA.
- Capsid
-
A proteinaceous shell that surrounds the viral genome.
- Vectors
-
Vehicles used to transfer nucleic acid information into the cell.
- Recombinase
-
An enzyme (for example, Cre or Flp) capable of recombining defined nucleic acid sequences, often used to activate or inactivate expression of a gene engineered to include sequences specific for that recombinase.
- Pseudotyping
-
The process of heterologously expressing proteins on a virus’ capsid/envelope (often with the intention of gaining advantageous viral spread/entry properties).
- Constructs
-
Designer DNA sequences.
- Cre-driver line
-
A mouse or rat strain (for example, knock-in and BAC transgenic) engineered to drive expression of Cre recombinase in a cell type-specific pattern (often using a marker gene’s promoter or enhancer elements).
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Nectow, A.R., Nestler, E.J. Viral tools for neuroscience. Nat Rev Neurosci 21, 669–681 (2020). https://doi.org/10.1038/s41583-020-00382-z
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DOI: https://doi.org/10.1038/s41583-020-00382-z
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