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author:("Lee, yulin")
1.  Structure of a Protozoan Virus from the Human Genitourinary Parasite Trichomonas vaginalis 
mBio  2013;4(2):e00056-13.
The flagellated protozoan Trichomonas vaginalis is an obligate human genitourinary parasite and the most frequent cause of sexually transmitted disease worldwide. Most clinical isolates of T. vaginalis are persistently infected with one or more double-stranded RNA (dsRNA) viruses from the genus Trichomonasvirus, family Totiviridae, which appear to influence not only protozoan biology but also human disease. Here we describe the three-dimensional structure of Trichomonas vaginalis virus 1 (TVV1) virions, as determined by electron cryomicroscopy and icosahedral image reconstruction. The structure reveals a T = 1 capsid comprising 120 subunits, 60 in each of two nonequivalent positions, designated A and B, as previously observed for fungal Totiviridae family members. The putative protomer is identified as an asymmetric AB dimer consistent with either decamer or tetramer assembly intermediates. The capsid surface is notable for raised plateaus around the icosahedral 5-fold axes, with canyons connecting the 2- and 3-fold axes. Capsid-spanning channels at the 5-fold axes are unusually wide and may facilitate release of the viral genome, promoting dsRNA-dependent immunoinflammatory responses, as recently shown upon the exposure of human cervicovaginal epithelial cells to either TVV-infected T. vaginalis or purified TVV1 virions. Despite extensive sequence divergence, conservative features of the capsid reveal a helix-rich fold probably derived from an ancestor shared with fungal Totiviridae family members. Also notable are mass spectrometry results assessing the virion proteins as a complement to structure determination, which suggest that translation of the TVV1 RNA-dependent RNA polymerase in fusion with its capsid protein involves −2, and not +1, ribosomal frameshifting, an uncommonly found mechanism to date.
Trichomonas vaginalis causes ~250 million new cases of sexually transmitted disease each year worldwide and is associated with serious complications, including premature birth and increased transmission of other pathogens, including HIV. It is an extracellular parasite that, in turn, commonly hosts infections with double-stranded RNA (dsRNA) viruses, trichomonasviruses, which appear to exacerbate disease through signaling of immunoinflammatory responses by human epithelial cells. Here we report the first three-dimensional structure of a trichomonasvirus, which is also the first such structure of any protozoan dsRNA virus; show that it has unusually wide channels at the capsid vertices, with potential for releasing the viral genome and promoting dsRNA-dependent responses by human cells; and provide evidence that it uses −2 ribosomal frameshifting, an uncommon mechanism, to translate its RNA polymerase in fusion with its capsid protein. These findings provide both mechanistic and translational insights concerning the role of trichomonasviruses in aggravating disease attributable to T. vaginalis.
PMCID: PMC3622925  PMID: 23549915
2.  Association between the BDNF Val66Met Polymorphism and Chronicity of Depression 
Psychiatry Investigation  2013;10(1):56-61.
Both clinical and biological factors influence the course of depressive disorders. This study tested for associations between the brain-derived neurotrophic factor (BDNF) gene at the Val66Met locus and the course of major depressive disorder (MDD).
Three hundred ten Korean subjects (209 patients, 101 controls) were genotyped for rs6265 at nucleotide 196 (G/A), which produces an amino acid substitution at codon 66 (Val66Met) of the gene for BDNF. Course of illness was evaluated both by chronicity of current episode (episode duration >24 months) and by the lifetime history of recurrences.
Patients with the Met/Met BDNF genotype had a significantly higher rate of chronic depression than all others. There was a significant dose effect of the Met allele on chronicity. Compared with the Val/Val genotype, the relative risk of chronicity was 1.67 for the Val/Met genotype, and 2.58 for the Met/Met genotype. Lifetime history of recurrent episodes was not related to BDNF genotypes but was significantly associated with younger age of onset and with a history of depression in first degree relatives.
BDNF genotyping may be informative for anticipating chronicity in major depression.
PMCID: PMC3590431  PMID: 23482723
Brain-derived neurotrophic factor (BDNF); BDNF Val66Met; Major depressive disorder; Clinical course; Chronicity; Recurrent depression
3.  G1/S Cell Cycle Checkpoint Defect in Lymphocytes from Patients with Alzheimer's Disease 
Psychiatry Investigation  2012;9(4):413-417.
We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimer's disease (AD) and normal controls to assess the early phase control defect in cell cycle.
Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin.
The patients with AD were older than the normal controls (AD 74.03±7.90 yr vs. control 68.28±6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29±6.32% vs. 76.03±9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45±6.09% vs. 6.03±5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects.
The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death.
PMCID: PMC3521120  PMID: 23251208
Alzheimer's disease; Cell cycle; Biomarker
4.  Endobiont Viruses Sensed by the Human Host – Beyond Conventional Antiparasitic Therapy 
PLoS ONE  2012;7(11):e48418.
Wide-spread protozoan parasites carry endosymbiotic dsRNA viruses with uncharted implications to the human host. Among them, Trichomonas vaginalis, a parasite adapted to the human genitourinary tract, infects globally ∼250 million each year rendering them more susceptible to devastating pregnancy complications (especially preterm birth), HIV infection and HPV-related cancer. While first-line antibiotic treatment (metronidazole) commonly kills the protozoan pathogen, it fails to improve reproductive outcome. We show that endosymbiotic Trichomonasvirus, highly prevalent in T. vaginalis clinical isolates, is sensed by the human epithelial cells via Toll-like receptor 3, triggering Interferon Regulating Factor -3, interferon type I and proinflammatory cascades previously implicated in preterm birth and HIV-1 susceptibility. Metronidazole treatment amplified these proinflammatory responses. Thus, a new paradigm targeting the protozoan viruses along with the protozoan host may prevent trichomoniasis-attributable inflammatory sequelae.
PMCID: PMC3492353  PMID: 23144878
5.  Serotonin Transporter Gene Polymorphisms and Chronic Illness of Depression 
Journal of Korean Medical Science  2010;25(12):1824-1827.
Clinical course of depression is variable. The serotonin transporter gene is one of the most studied genes for depression. We examined the association of serotonin transporter gene polymorphisms with chronicity and recurrent tendency of depression in Korean subjects. This cross-sectional study involved 252 patients with major depression. Patients were genotyped for s/l polymorphisms in 5-HTT promoter region (5-HTTLPR), s/l variation in second intron of the 5-HTT gene (5-HTT VNTR intron2). Chronicity was associated with 5-HTTLPR. Patients with l/l had higher rate of chronicity than the other patients (l/l vs s/l or s/s; odds ratio, 4.45; 95% confidence interval, 1.59-12.46; P=0.005; logistic regression analysis). Recurrent tendency was not associated with 5-HTTLPR. Chronicity and recurrent tendency were not associated with 5-HTT VNTR intron2. These results suggest that chronic depression is associated with 5-HTTLPR.
PMCID: PMC2995243  PMID: 21165304
Depression; 5-Hydroxytryptamine Transporter

Results 1-5 (5)