Genetic and phylogenetic characterizations of a novel genotype of highly pathogenic avian influenza (HPAI) H5N8 viruses in 2016/2017 in South Korea

Kim, Y.I.,Park, S.J.,Kwon, H.I.,Kim, E.H.,Si, Y.J.,Jeong, J.H.,Lee, I.W.,Nguyen, H.D.,Kwon, J.J.,Choi, W.S.,Song, M.S.,Kim, C.J.,Choi, Y.K. Elsevier Science 2017 INFECTION GENETICS AND EVOLUTION Vol.53 No.-

<P>During the outbreaks of highly pathogenic avian influenza (HPAI) H5N6 viruses in 2016 in South Korea, novel H5N8 viruses were also isolated from migratory birds. Phylogenetic analysis revealed that the HA gene of these H5N8 viruses belonged to clade 2.3.4.4, similarly to recent H5Nx viruses, and originated from A/Brk/Korea/Gochang1/14(H5N8), a minor lineage of H5N8 that appeared in 2014 and then disappeared. At least four reassortment events occurred with different subtypes (H5N8, H7N7, H3N8 and H10N7) and a chicken challenge study revealed that they were classified as HPAI viruses according to OIE criteria. (C) 2017 Elsevier B.V. All rights reserved.</P>

Supplementation of oil-based inactivated H9N2 vaccine with M2e antigen enhances resistance against heterologous H9N2 avian influenza virus infection

Park, J.K.,Lee, D.H.,Cho, C.H.,Yuk, S.S.,To, E.O.,Kwon, J.H.,Noh, J.Y.,Kim, B.Y.,Choi, S.W.,Shim, B.S.,Song, M.K.,Lee, J.B.,Park, S.Y.,Choi, I.S.,Song, C.S. Elsevier Scientific Pub. Co 2014 Veterinary microbiology Vol.169 No.3

Avian influenza virus (AIV) subtype H9N2 has been evolving rapidly and vaccine escape variants have been reported to cause circulation of infections and economic losses. In the present study, we developed and evaluated ectodomain of the AIV matrix 2 (M2e) protein as a supplementing antigen for oil-based inactivated H9N2 vaccine to increase resistance against vaccine escape variants. AIV H9N2 M2e antigen was expressed in Escherichia coli and supplemented to inactivated H9N2 oil emulsion vaccine. Specific pathogen-free chickens received a single injection of inactivated H9N2 oil emulsion vaccines with or without M2e supplementation. At three weeks post vaccination, hemagglutination inhibition tests and enzyme-linked immunosorbent assays were performed to determine serological immune responses. Challenge study using a vaccine escape H9N2 variant was performed to evaluate the efficacy of M2e supplementation. M2e antigen supplemented in oil emulsion vaccine was highly immunogenic, and a single M2e-supplemented vaccination reduced challenge virus replication and shedding more effectively than non-supplemented vaccination.

Time-dependent effects of Klebsiella pneumoniae endotoxin on the pharmacokinetics of chlorzoxazone and its main metabolite, 6-hydroxychlorzoxazone, in rats: restoration of the parameters in 96 hour in KPLPS rats to control levels

Jung, Hye Y.,Kang, Hee E.,Choi, Young H.,Kim, So H.,Lee, Myung G. John Wiley Sons, Ltd. 2009 BIOPHARMACEUTICS AND DRUG DISPOSITION Vol.30 No.8

<P>It has been reported that chlorzoxazone (CZX) was primarily metabolized via hepatic Cyp2e1 to form 6-hydroxychlorzoxazone (OH-CZX) in rats, and the activity of aniline hydroxylase (a Cyp2e1 marker) in the liver was significantly decreased in rats at 24 h after pretreatment with lipopolysaccharide derived from Klebsiella pneumoniae (24 h KPLPS rats), whereas the levels were not changed at 2 h and 96 h in the KPLPS rats. Thus, the time-dependent pharmacokinetic parameters of CZX and OH-CZX were evaluated after the intravenous administration of CZX (20 mg/kg) to control rats, and the 2 h, 24 h and 96 h KPLPS rats along with the time-dependent changes in the protein expression of hepatic Cyp2e1. After the intravenous administration of CZX to 24 h KPLPS rats, the AUC<SUB>0–2 h</SUB> of OH-CZX and AUC<SUB>OH-CZX, 0–2 h</SUB>/AUC<SUB>CZX</SUB> were significantly smaller (by 40.5% and 71.2%, respectively) than those of controls due to the significant decrease (by 75.3%) in the protein expression of hepatic Cyp2e1. However, in 96 h KPLPS rats, the pharmacokinetic parameters of both CZX and OH-CZX were unchanged compared with controls due to the restoration of the protein expression of hepatic Cyp2e1 to control levels. These observations highlighted the existence of the time-dependent effects of KPLPS on the pharmacokinetics of CZX and OH-CZX in rats. Copyright © 2009 John Wiley & Sons, Ltd.</P>

Neural stem cells injured by oxidative stress can be rejuvenated by GV1001, a novel peptide, through scavenging free radicals and enhancing survival signals

Park, H.H.,Yu, H.J.,Kim, S.,Kim, G.,Choi, N.Y.,Lee, E.H.,Lee, Y.J.,Yoon, M.Y.,Lee, K.Y.,Koh, S.H. Elsevier BV 2016 NeuroToxicology Vol.55 No.-

<P>Oxidative stress is a well-known pathogenic mechanism of a diverse array of neurological diseases, and thus, numerous studies have attempted to identify antioxidants that prevent neuronal cell death. GV1001 is a 16-amino-acid peptide derived from human telomerase reverse transcriptase (hTERT). Considering that hTERT has a strong antioxidant effect, whether GV1001 also has an antioxidant effect is a question of interest. In the present study, we aimed to investigate the effects of GV1001 against oxidative stress in neural stem cells (NSCs). Primary culture NSCs were treated with different concentrations of GV1001 and/or hydrogen peroxide (H2O2) for various time durations. The H2O2 decreased the viability of the NSCs in a concentration-dependent manner, with 200 mu M H2O2 significantly decreasing both proliferation and migration. However, treatment with GV1001 rescued the viability, proliferation and migration of H2O2 injured NSCs. Consistently, free radical levels were increased in rat NSCs treated with H2O2, while co-treatment with GV1001 significantly reduced these levels, especially the intracellular levels. In addition, GV1001 restored the expression of survival-related proteins and reduced the expression of death associated ones in NSCs treated with H2O2. In conclusion, GV1001 has antioxidant and neuroprotective effects in NSCs following treatment with H2O2, which appear to be mediated by scavenging free radicals, increasing survival signals and decreasing death signals. (C) 2016 Elsevier B.V. All rights reserved.</P>

NMR study of hydrogen exchange during the B-Z transition of a DNA duplex induced by the Zα domains of yatapoxvirus E3L

Lee, E.H.,Seo, Y.J.,Ahn, H.C.,Kang, Y.M.,Kim, H.E.,Lee, Y.M.,Choi, B.S.,Lee, J.H. North-Holland Pub ; Elsevier Science Ltd 2010 FEBS letters Vol.584 No.21

The Yaba-like disease viruses (YLDV) are members of the Yatapoxvirus family and have double-stranded DNA genomes. The E3L protein, which is essential for pathogenesis in the vaccinia virus, consists of two domains: an N-terminal Z-DNA binding domain and a C-terminal RNA binding domain. The crystal structure of the E3L orthologue of YLDV (yabZα<SUB>E3L</SUB>) bound to Z-DNA revealed that the overall structure of yabZα<SUB>E3L</SUB> and its interaction with Z-DNA are very similar to those of hZα<SUB>ADAR1</SUB>. Here we have performed NMR hydrogen exchange experiments on the complexes between yabZα<SUB>E3L</SUB> and d(CGCGCG)<SUB>2</SUB> with a variety of protein-to-DNA molar ratios. This study revealed that yabZα<SUB>E3L</SUB> could efficiently change the B-form helix of the d(CGCGCG)<SUB>2</SUB> to left-handed Z-DNA via the active-mono B-Z transition pathway like hZα<SUB>ADAR1</SUB>1.

Nanoparticulate zero-valent iron coupled with polyphosphate: the sequential redox treatment of organic compounds and its stability and bacterial toxicity

Kim, H. H.,Kim, M.,Kim, H. E.,Lee, H. J.,Jang, M. H.,Choi, J.,Hwang, Y.,Lee, C. RSC 2017 Environmental science Vol.4 No.2

<P>Nanoparticulate zero-valent iron (nZVI) coupled with tetrapolyphosphate (TPP) (nZVI/TPP) was examined for the degradation of organic compounds, such as trichloroethylene (TCE), pentachlorophenol (PCP), and phenol, and the effects of TPP on the stability and toxicity of nZVI were studied. A sequential redox treatment (i.e., anoxic followed by oxic treatment) was attempted as a means to improve the utilization of nZVI for compound degradation. In the first anoxic treatment, chlorinated organic compounds, such as TCE and PCP, were degraded reductively by electron transfer from nZVI to the compounds at relatively slow rates. In the following oxic treatment, all organic compounds were rapidly degraded by the reactive oxidant (Fe(IV) species) produced via the reaction of the Fe(II)-TPP complexes with oxygen. In both anoxic and oxic treatment stages, the nZVI/TPP system exhibited greater activity in the degradation of organic compounds than that of nZVI alone. The anoxic/oxic reactivity of nZVI/TPP was affected by the pH and nZVI dose. The coupling of nZVI with TPP also enhanced the stability of nZVI; TPP was observed to inhibit the agglomeration and sedimentation of nZVI. In addition, the bacterial toxicity of nZVI and its oxidation products (i.e., Fe(II) and Fe(III)) was significantly reduced by the addition of TPP; TPP lowered the degree of E. coli inactivation by nZVI and its products, mitigating cell membrane damage.</P>

Surveillance of avian influenza virus in wild bird fecal samples from South Korea, 2003-2008.

Kang, H M,Jeong, O M,Kim, M C,Kwon, J S,Paek, M R,Choi, J G,Lee, E K,Kim, Y J,Kwon, J H,Lee, Y J [Wildlife Disease Association] 2010 JOURNAL OF WILDLIFE DISEASES Vol.46 No.3

<P>We analyzed the results from nationwide surveillance of avian influenza (AI) from birds in South Korea's major wild bird habitats and the demilitarized zone of South Korea, 2003-2008. Of 28,214 fecal samples analyzed, 225 yielded influenza viruses, for a prevalence of 0.8%. Hemagglutinin (HA) subtypes H1-H12 and all nine neuraminidase (NA) subtypes were detected. The dominant HA subtypes were H6, H1, and H4, and the most common NA subtypes were N2, N1, and N6. Among the 38 HA/NA subtype combinations, the most common were H4N6, H6N1, and H5N2. Thirty-seven low-pathogenic AI (LPAI) viruses of the H5 and H7 subtype were detected. Among them, we identified bird species for 16 H5- and H7-positive fecal samples using a DNA bar-coding system instituted in 2007; all birds were identified as Anseriformes. The HA gene of the H5 wild bird isolates belonged to the Eurasian avian lineage, and could be clearly distinguished from the sublineage H5N1 highly pathogenic AI (HPAI) of the Eurasian and American avian lineages. Whereas H7 LPAI viruses did not group as a separate sublineage with H7 HPAI viruses, H7 isolates were closely related with the Eurasian avian lineage.</P>

Rapid expression of RASD1 is regulated by estrogen receptor-dependent intracellular signaling pathway in the mouse uterus

Kim, H.R.,Cho, K.S.,Kim, E.,Lee, O.H.,Yoon, H.,Lee, S.,Moon, S.,Park, M.,Hong, K.,Na, Y.,Shin, J.E.,Kwon, H.,Song, H.,Choi, D.H.,Choi, Y. North-Holland 2017 Molecular and cellular endocrinology Vol.446 No.-

<P>Dexamethasone-induced RAS-related protein 1 (RASD1) is a signaling protein that is involved in various cellular processes. In a previous study, we found that RASD1 expression was down-regulated in the uterine endometrium of repeated implantation failure patients. The study aim was to determine whether RASD1 is expressed in the endometrium of mouse uterus and how it is regulated by steroid hormones during the estrous cycle. In this study, we investigated RASD1 expression and regulation in an ovariectomized female mouse model. Rasdl mRNA was highly expressed in mouse reproductive tissues, including the uterus. Rasdl expression was detected exclusively in the endometrial epithelium at the proestrus stage of the estrous cycle. Rasd1 expression in uteri increased with administration of estradiol, but not progesterone. Its expression was rapidly induced within 2 h after E2 treatment. Pretreatment with ICI 182,780, an estrogen receptor antagonist, reduced RASD1 protein expression. In addition, we identified that rapid expression of Rasd1 was mediated by the estrogen intracellular signaling including both p38-mitogen-activated protein kinase and the extracellular signal-regulated kinase. These findings suggest that RASD1 acts as a novel signaling molecule and plays an important role in regulating dynamic uterine remodeling during the estrous cycle in the uterus. (C) 2017 Elsevier B.V. All rights reserved.</P>

Cross-protective efficacies of highly-pathogenic avian influenza H5N1 vaccines against a recent H5N8 virus

Park, S.J.,Si, Y.J.,Kim, J.,Song, M.S.,Kim, S.m.,Kim, E.H.,Kwon, H.i.,Kim, Y.I.,Lee, O.J.,Shin, O.S.,Kim, C.J.,Shin, E.C.,Choi, Y.K. Academic Press 2016 Virology Vol.498 No.-

<P>To investigate cross-protective vaccine efficacy of highly-pathogenic avian influenza H5N1 viruses against a recent HPAI H5N8 virus, we immunized C57BL/6 mice and ferrets with three alum-adjuvanted inactivated whole H5N1 vaccines developed through reverse-genetics (Rg): [Vietnam/1194/04xPR8 (clade 1), Korea/W149/06xPR8 (clade 2.2), and Korea/ES223N/03xPR8 (clade 2.5)]. Although relatively low cross-reactivities (10-40 HI titer) were observed against heterologous H5N8 virus, immunized animals were 100% protected from challenge with the 20 mLD(50) of H5N8 virus, with the exception of mice vaccinated with 3.5 mu g of Rg Vietnam/1194/04xPR8. Of note, the Rg Korea/ES223N/03xPR8 vaccine provided not only effective protection, but also markedly inhibited viral replication in the lungs and nasal swabs of vaccine recipients within five days of HPAI H5N8 virus challenge. Further, we demonstrated that antibody-dependent cell-mediated cytotoxicity (ADCC) of an antibody-coated target cell by cytotoxic effector cells also plays a role in the heterologous protection of H5N1 vaccines against H5N8 challenge. (C) 2016 Elsevier Inc. All rights reserved.</P>

Blocking the immunosuppressive axis with small interfering RNA targeting interleukin (IL)‐10 receptor enhances dendritic cell‐based vaccine potency

Kim, J. H.,Kang, T. H.,Noh, K. H.,Bae, H. C.,Ahn, Y‐,H.,Lee, Y‐,H.,Choi, E. Y.,Chun, K‐,H.,Lee, S‐,J.,Kim, T. W. Blackwell Publishing Ltd 2011 Clinical and experimental immunology Vol.165 No.2

<P><B>Summary</B></P><P>Improving dendritic cell (DC) functions is highly promising for therapeutic intervention of diverse diseases, including cancer. Immunosuppressive cytokines such as interleukin (IL)‐10 produced by DCs themselves (autocrine) and other regulatory immune cells (paracrine) down‐regulate functional profiles of DCs through specific cell surface receptors such as IL‐10R. Here, we tried to improve DC functions using small interfering RNA (siRNA) technology to block an IL‐10R‐mediated immunosuppressive axis. DCs modified with siRNA targeting against IL‐10R or IL‐10 (DC/siIL‐10R or DC/siIL‐10) led to up‐regulation of major histocompatibility complex (MHC) class II, CD40 co‐stimulatory molecule, and IL‐12 proinflammatory cytokine after lipopolysacharide (LPS) stimulation compared to DC/siGFP. Notably, the LPS‐induced functional profiles of DC/siIL‐10R were strongly resistant to the addition of recombinant IL‐10, which mimicked paracrine IL‐10. In contrast, those of DC/siIL‐10 were reversed by adding exogenous IL‐10. Consistently, DC/siIL‐10R generated more human papilloma virus (HPV) E7‐specific CD8<SUP>+</SUP> T cells and stronger anti‐tumour effects against E7‐expressing TC‐1 tumour cells in vaccinated mice than DC/siGFP, as well as DC/siIL‐10. Taken together, these results provide the groundwork for future clinical translation of siRNA‐mediated strategy targeting IL‐10R to enhance DC‐based vaccine potency.</P>