promoter in an adult animal. By having
control over the time of injection, the use
of viruses can sidestep the issue of devel-
opmental genetic dynamics. Additionally,
this method also potentially allows control
of the amount of expression by varying
the virus titer and injection volume. Lastly,
this method is tremendously cheaper and
faster than creating and maintaining col-
onies of transgenic animals. Similar ap-
proaches have already been shown to
be effective in rats (Mikhailova et al.,
2016 ). Other methods for attaining cell-
type specificity using only viruses in ro-
dents employ pathway-specific injections
of viruses or the creation of synthetic pro-
moters (Zalocusky et al., 2016). Neither of
these methods are easy to generalize to
multiple cell types.
The method presented here also has
some significant limitations. The most
important one is that AAVs can only deliver
small genetic payloads. Thus, when
endogenous promoters are large (TH, for
instance, is7kbp long), modified ver-
sions of these promoters need to be
used. This may require a lot of trial and er-
ror depending on the promoter, though
this process could be sped up by testing
thepromoterfragmentsinmiceorpossibly
cell culture. One way to overcome the lim-
itation in size of the promoter is to use
viruses with larger packaging capacities
for gene transfer such as lentiviruses.
Another limitation is that the amount of
expression of the protein of interest can
be quite heterogeneous across infected
cells when compared to transgenic ani-
mals. Lastly, one has to spend significant
effort in determining the best viruses for
infecting each cell type of interest, and in
some cases, there may be no available
virus combination for targeting a specific
cell type.
In sum, the methods presented by
Stauffer et al. (2016)will hopefully lead to
the advent of cell-type-specific neuronal
studies in monkeys. Further, in animals
such as mice for which genetic methods
are already established, this approach
may potentially result in the development
of better virus-based methods that could
dramatically reduce the cost and speed
of attaining cell-type specificity. Never-
theless, this method needs to be repli-
cated in other cell types in order to have
long-term impact.ACKNOWLEDGMENTSWe would like to acknowledge funding support
from the Helen Lyng White Fellowship (V.M.K.N.),The Foundation of Hope, the Brain and Behavior
Research Foundation, and the National Institute
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Give Your Brain Something Good to Eat
Janelle S. Ayres1,*
(^1) Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road,
La Jolla, CA 92037, USA
*Correspondence:[email protected]
http://dx.doi.org/10.1016/j.cell.2016.08.034
The reprioritization of feeding motivations during disease is proposed to optimize host defense
strategies against infection. Now, Wang et al. identify that sickness-induced anorexia differentially
shapes the metabolic requirements of cellular stress adaptations, leading to opposite impact on
disease tolerance upon bacterial versus viral infections.
Many of us may remember hearing our
mother reciting the old proverb ‘‘feed a
cold, starve a fever.’’ Despite some his-
torical and linguistic debates about this
phrase, there may be something to it.
During infection, animals exhibit stereo-
typical behavioral changes, including
anorexia, changes in sleep patterns, so-
cial withdrawal, and changes in groom-
ing practices, collectively referred to as
‘‘sickness behaviors’’ (Hart, 1988). These
behaviors are highly conserved from
1368 Cell 166 , September 8, 2016ª2016 Elsevier Inc.