Using Viral-Mediated Gene Transfer to Study Depressive- Like Behavior - Viral Vector Approaches in Neurobiology and Brain Diseases - page 163

Table 1
Characteristics of different viral vectors

Lentivirus AV AAV HSV

Infl ammatory response Mild Strong Mild Moderate

Cell type specifi city Neurons and glia Neurons and glia Neurons and glia

(depends on strain)

Neurons

Integration into
host chromosome

Yes No Possibly No

Predictable site
of integration

No N/A Yes N/A

Titers Moderate Very high Very high Low

Insert size Can be large Must be small Can be large

Gene expression
time course

Prolonged
and stable

Prolonged
and stable

Transient gene
expression

Transient gene
expression

vector is replication defi cient, rapid onset of intense, albeit short-
term expression when using the HSV promoter, neuron specifi city,
high affi nity binding to its cellular recognition protein, and low
levels of retrograde infection (i.e., infection of axon terminals at the
site of vector infusion). Disadvantages include diffi culty achieving
high titers unless packaged with replication-defi cient helper virus,
expression dissipates after about 1 week (unless a non-HSV pro-
moter is used, see Ferguson and Neumaier chapter), fairly small
areas are transduced (usually less than 1 mm is infected per injec-
tion), and fewer neurons are infected than with other vectors.
However, each of these problems can be used to the investigator's
advantage. For example, the rapid onset and offset of transgene
expression allowed us to test the effects of increased 5-HT 1B auto-
receptor expression on the acquisition vs. expression of conditioned
fear [ 3 ]. Furthermore, the high affi nity binding and limited spread
of HSV is ideal for transducing genes into small brain regions.
Currently, AAV may be the most commonly used vector; it has the
advantages of very high titers with helper virus-free packaging,
long-term transgene expression, low infl ammatory responses, and
the availability of commercial packaging. On the other hand, only a
rather small payload can be incorporated (usually less than 3 kb),
different serotypes have varying effi ciency in infecting neurons vs.
glia, and lower affi nity for cellular binding leads to larger areas of
infection (but this can be an advantage as well). Some basic charac-
teristics of several common viral vectors are summarized in Table 1 .
Viral vectors offer a broad range of potential manipulations of
brain function. These include overexpression of an endogenous
protein such as a receptor, enzyme, or structural protein. In most