Metagenomic analysis of double-stranded DNA viruses in healthy adults.

The Human Microbiome Project (HMP) was undertaken with the
goal of defining microbial communities in and on the bodies of healthy
individuals using high-throughput, metagenomic sequencing analysis. The
viruses present in these microbial communities, the `human virome¿, are
an important aspect of the human microbiome that is particularly
understudied in the absence of overt disease. We analyzed eukaryotic
double-stranded DNA (dsDNA) viruses, together with dsDNA replicative
intermediates of single-stranded DNA viruses, in metagenomic sequence
data generated by the HMP. 706 samples from 102 subjects were studied,
with each subject sampled at up to five major body habitats: nose, skin,
mouth, vagina, and stool. Fifty-one individuals had samples taken at
two or three time points 30 to 359 days apart from at least one of the
body habitats.ResultsWe detected an average of 5.5 viral genera in each
individual. At least 1 virus was detected in 92% of the individuals
sampled. These viruses included herpesviruses, papillomaviruses,
polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and
circoviruses. Each individual had a distinct viral profile,
demonstrating the high interpersonal diversity of the virome. Some
components of the virome were stable over time.ConclusionsThis study is
the first to use high-throughput DNA sequencing to describe the
diversity of eukaryotic dsDNA viruses in a large cohort of normal
individuals who were sampled at multiple body sites. Our results show
that the human virome is a complex component of the microbial flora.
Some viruses establish long-term infections that may be associated with
increased risk or possibly with protection from disease. A better
understanding of the composition and dynamics of the virome may hold
important keys to human health.

Mice Genetically Depleted of Brain Serotonin Do Not Display a Depression-like Behavioral Phenotype - ACS Chemical Neuroscience

Reductions in function within the serotonin (5HT) neuronal system have
long been proposed as etiological factors in depression. Selective
serotonin reuptake inhibitors (SSRIs) are the most common treatment for
depression, and their therapeutic effect is generally attributed to
their ability to increase the synaptic levels of 5HT. Tryptophan
hydroxylase 2 (TPH2) is the initial and rate-limiting enzyme in the
biosynthetic pathway of 5HT in the CNS, and losses in its catalytic
activity lead to reductions in 5HT production and release. The time
differential between the onset of 5HT reuptake inhibition by SSRIs
(minutes) and onset of their antidepressant efficacy (weeks to months),
when considered with their overall poor therapeutic effectiveness, has
cast some doubt on the role of 5HT in depression. Mice lacking the gene
for TPH2 are genetically depleted of brain 5HT and were tested for a
depression-like behavioral phenotype using a battery of valid tests for
affective-like disorders in animals. The behavior of TPH2^–/–
mice on the sucrose preference test, tail suspension test, and forced
swim test and their responses in the unpredictable chronic mild stress
and learned helplessness paradigms was the same as wild-type controls.
While TPH2^–/– mice as a group were not responsive to SSRIs, a
subset responded to treatment with SSRIs in the same manner as
wild-type controls with significant reductions in immobility time on the
tail suspension test, indicative of antidepressant drug effects. The
behavioral phenotype of the TPH2^–/– mouse questions the role of 5HT in depression. Furthermore, the TPH2^–/–
mouse may serve as a useful model in the search for new medications
that have therapeutic targets for depression that are outside of the 5HT
neuronal system.