Using Viral-Mediated Gene Transfer to Study Depressive- Like Behavior - Viral Vector Approaches in Neurobiology and Brain Diseases - page 162

to the vectors. This may require devising a system that alerts ani-
mal care personnel to the presence of virus, while maintaining
blinded conditions and preserving the integrity of the experiment
for those collecting data. In our lab, we have dealt with this by
treating every cage in an experiment as if the animals have been
exposed to virus (i.e., even if it was a sham or vehicle injection).
These types of issues dictate where the animals live (special BSL-
dedicated housing or in the general population), as well the proce-
dure for disposing of soiled bedding. High expectations for detail
extend beyond just animal care. Finally, just as each drug used in a
behavioral experiment must be described in an approved protocol,
the type of virus and the nature of the transgenes encoded by the
vector must be detailed; this can become a regulatory burden for
both the investigator and the institutional committees overseeing
the research procedures.

3 Considerations in Choosing a Vector

3.1 Overview

There are several common viral vectors from which to choose,
including Herpes Simplex Virus type 1 (HSV), lentivirus, adenovi-
rus (AV), adeno-associated virus (AAV), and canine adenovirus-2
(CAV). Use of these vectors in the CNS has been extensively
reviewed [ 1 ]. Many factors will dictate which vector is best to use,
including safety for the user, the vector's ability to induce an infl am-
matory response, and cell type infection specifi city. Many individu-
als choose a particular viral vector based on their familiarity with the
tool, advice from colleagues, or the convenience of packaging. Each
of these vectors has advantages and disadvantages, and in most
cases, more than one will work well for a particular experimental
plan. In the end, the virus that is the safest and most effective, for
both laboratory personnel and animals, and that appropriately
expresses in the model system should be used. Some vectors are
highly versatile and adaptable to different needs and others are
more restricted in their potential. Characteristics to consider are
cellular infectivity (which cell types or stages can be targeted), titer,
time course of transgene expression, “payload” capacity, chromo-
somal integration (if the gene becomes incorporated into the host
genome), and for vectors that do not integrate, cytoplasmic stability
(how long a nonintegrated gene is actively transcribed); also the
size of the gene or genes that can be packaged for transmission can
be an issue. Table 1 compares characteristics of the different viruses
that are commonly used in behavioral neuroscience research.
We have been using HSV for a number of years and it has been
reviewed previously; this vector system has been reviewed previ-
ously [ 2 ]. Some advantages of this vector include its relatively large
payload capacity (at least 5 kb and potentially much more), BSL-1
containment practices after confi rming that the particular batch of