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Virology
Modeling Williams syndrome with induced pluripotent stem cells
Feb 23, 2017   Neurogenesis (Austin, Tex.)
Chailangkarn T, Muotri AR
Modeling Williams syndrome with induced pluripotent stem cells
Feb 23, 2017
Neurogenesis (Austin, Tex.)
The development of induced pluripotent stem cells (iPSCs) like never before has opened novel opportunity to study diseases in relevant cell types. In our recent study, Williams syndrome (WS), a rare genetic neurodevelopmental disorder, that is caused by hemizygous deletion of 25-28 genes on chromosome 7, is of interest because of its unique cognitive and social profiles. Little is known about haploinsufficiency effect of those deleted genes on molecular and cellular phenotypes at the neural level due to the lack of relevant human cellular model. Using the cellular reprogramming approach, we reported that WS iPSC-derived neural progenitor cells (NPCs) has increased apoptosis and therefore increased doubling time, which could be rescued by complementation of frizzled 9, one of the genes typically deleted in WS. Moreover, WS iPSC-derived CTIP2-positive pyramidal neurons exhibit morphologic alterations including longer total dendrites and increasing dendritic spine number. In addition, WS iPSC-derived neurons show an increase in calcium transient frequency and synchronized activity likely due to increased number of dendritic spines and synapses. Our work integrated cross-level data from genetics to behavior of WS individuals and revealed altered cellular phenotypes in WS human NPCs and neurons that could be validated in other model systems such as magnetic resonance imaging (MRI) in live subjects and postmortem brain tissues.
Alteration of N-glycan expression profile and glycan pattern of glycoproteins in human hepatoma cells after HCV infection
Feb 23, 2017   Biochimica Et Biophysica Acta
Xiang T, Yang G, Liu X, Zhou Y, Fu Z, Lu F, Gu J, Taniguchi N, Tan Z, Chen X, Xie Y, Guan F, Zhang XL
Alteration of N-glycan expression profile and glycan pattern of glycoproteins in human hepatoma cells after HCV infection
Feb 23, 2017
Biochimica Et Biophysica Acta
BACKGROUND: Hepatitis C virus (HCV) infection causes chronic liver diseases, liver fibrosis and even hepatocellular carcinoma (HCC). However little is known about any information of N-glycan pattern in human liver cell after HCV infection. METHODS: The altered profile of N-glycans in HCV-infected Huh7.5.1 cell were analyzed by using mass spectrometry. Then, lectin microarray, lectin pull-down assay, reverse transcription-quantitative real time PCR (RT-qPCR) and western-blotting were used to identify the altered N-glycosylated proteins and glycosyltransferases. RESULTS: Compared to uninfected cells, significantly elevated levels of fucosylated, sialylated and complex N-glycans were found in HCV infected cells. Furthermore, Lens culinaris agglutinin (LCA)-binding glycoconjugates were increased most. Then, the LCA-agarose was used to precipitate the specific glycosylated proteins and identify that fucosylated modified annexin A2 (ANXA2) and heat shock protein 90 beta family member 1 (HSP90B1) was greatly increased in HCV-infected cells. However, the total ANXA2 and HSP90B1 protein levels remained unchanged. Additionally, we screened the mRNA expressions of 47 types of different glycosyltransferases and found that α1,6-fucosyltransferase 8 (FUT8) was the most up-regulated and contributed to strengthen the LCA binding capability to fucosylated modified ANXA2 and HSP90B1 after HCV infection. CONCLUSIONS: HCV infection caused the altered N-glycans profiles, increased expressions of FUT8, fucosylated ANXA2 and HSP90B1 as well as enhanced LCA binding to Huh7.5.1. GENERAL SIGNIFICANCE: Our results may lay the foundation for clarifying the role of N-glycans and facilitate the development of novel diagnostic biomarkers and therapeutic targets based on the increased FUT8, fucosylated ANXA2 and HSP90B1 after HCV infection. Copyright © 2017. Published by Elsevier B.V.
Human Enterovirus 68 Interferes with the Host Cell Cycle to Facilitate Viral Production
Feb 23, 2017   Frontiers In Cellular And Infection Microbiology
Wang ZY, Zhong T, Wang Y, Song FM, Yu XF, Xing LP, Zhang WY, Yu JH, Hua SC, Yu XF
Human Enterovirus 68 Interferes with the Host Cell Cycle to Facilitate Viral Production
Feb 23, 2017
Frontiers In Cellular And Infection Microbiology
Enterovirus D68 (EV-D68) is an emerging pathogen that recently caused a large outbreak of severe respiratory disease in the United States and other countries. Little is known about the relationship between EV-D68 virus and host cells. In this study, we assessed the effect of the host cell cycle on EV-D68 viral production, as well as the ability of EV-D68 to manipulate host cell cycle progression. The results suggest that synchronization in G0/G1 phase, but not S phase, promotes viral production, while synchronization in G2/M inhibits viral production. Both an early EV-D68 isolate and currently circulating strains of EV-D68 can manipulate the host cell cycle to arrest cells in the G0/G1 phase, thus providing favorable conditions for virus production. Cell cycle regulation by EV-D68 was associated with corresponding effects on the expression of cyclins and CDKs, which were observed at the level of the protein and/or mRNA. Furthermore, the viral non-structural protein 3D of EV-D68 prevents progression from G0/G1 to S. Interestingly, another member of the
Feb 23, 2017   Frontiers In Cellular And Infection Microbiology
Cabezas-Cruz A, Alberdi P, Valdés JJ, Villar M, de la Fuente J
Feb 23, 2017
Frontiers In Cellular And Infection Microbiology
The obligate intracellular pathogen,
ER protein SCAP inhibits Dengue virus NS2B3 protease by suppressing its K27-linked polyubiquitylation
Feb 23, 2017   Journal Of Virology
Liu H, Zhang L, Sun J, Chen W, Li S, Wang Q, Yu H, Xia Z, Jin X, Wang C
ER protein SCAP inhibits Dengue virus NS2B3 protease by suppressing its K27-linked polyubiquitylation
Feb 23, 2017
Journal Of Virology
Dengue viruses (DENVs) are an emerging threat to global public health. The NS2B3 protease complex of DENV has recently been shown to cleave antiviral protein STING and thereby subverting the innate immune signaling to facilitate virus replication. Whether host cells have mechanism to counteract this virus-mediated immunosuppression is unclear. We discovered that the K27-linked poly-ubiquitination of NS3 protein facilitates its recruitment of NS2B and the formation of NS2B3, and consequently the enhanced cleavage of STING. However, an ER protein SCAP, through binding to NS2B protein, inhibits the ubiquitination of NS3, rendering NS2B3 protease incapable of binding and cleavage of STING. Importantly, ectopic-expression of SCAP impaired DENV infection, whereas silencing of SCAP potentiated DENV infection. Collectively, this study uncovered a novel function of SCAP to counteract the inhibitory action of DENV NS2B3 protease on the STING signaling, suggesting that modulation of SCAP levels may have therapeutic implications.Copyright © 2017 American Society for Microbiology.
Phylogenetic Characterizations of Highly Mutated EV-B106 Recombinants Showing Extensive Genetic Exchanges with Other EV-B in Xinjiang, China
Feb 23, 2017   Scientific Reports
Song Y, Zhang Y, Fan Q, Cui H, Yan D, Zhu S, Tang H, Sun Q, Wang D, Xu W
Phylogenetic Characterizations of Highly Mutated EV-B106 Recombinants Showing Extensive Genetic Exchanges with Other EV-B in Xinjiang, China
Feb 23, 2017
Scientific Reports
Human enterovirus B106 (EV-B106) is a new member of the enterovirus B species. To date, only three nucleotide sequences of EV-B106 have been published, and only one full-length genome sequence (the Yunnan strain 148/YN/CHN/12) is available in the GenBank database. In this study, we conducted phylogenetic characterisation of four EV-B106 strains isolated in Xinjiang, China. Pairwise comparisons of the nucleotide sequences and the deduced amino acid sequences revealed that the four Xinjiang EV-B106 strains had only 80.5-80.8% nucleotide identity and 95.4-97.3% amino acid identity with the Yunnan EV-B106 strain, indicating high mutagenicity. Similarity plots and bootscanning analyses revealed that frequent intertypic recombination occurred in all four Xinjiang EV-B106 strains in the non-structural region. These four strains may share a donor sequence with the EV-B85 strain, which circulated in Xinjiang in 2011, indicating extensive genetic exchanges between these strains. All Xinjiang EV-B106 strains were temperature-sensitive. An antibody seroprevalence study against EV-B106 in two Xinjiang prefectures also showed low titres of neutralizing antibodies, suggesting limited exposure and transmission in the population. This study contributes the whole genome sequences of EV-B106 to the GenBank database and provides valuable information regarding the molecular epidemiology of EV-B106 in China.
PreC and C Regions of Woodchuck Hepatitis Virus Facilitate Persistent Expression of Surface Antigen of Chimeric WHV-HBV Virus in the Hydrodynamic Injection BALB/c Mouse Model
Feb 23, 2017   Viruses
Wu W, Liu Y, Lin Y, Pan D, Yang D, Lu M, Xu Y
PreC and C Regions of Woodchuck Hepatitis Virus Facilitate Persistent Expression of Surface Antigen of Chimeric WHV-HBV Virus in the Hydrodynamic Injection BALB/c Mouse Model
Feb 23, 2017
Viruses
In the hydrodynamic injection (HI) BALB/c mouse model with the overlength viral genome, we have found that woodchuck hepatitis virus (WHV) could persist for a prolonged period of time (up to 45 weeks), while hepatitis B virus (HBV) was mostly cleared at week four. In this study, we constructed a series of chimeric genomes based on HBV and WHV, in which the individual sequences of a 1.3-fold overlength HBV genome in pBS-HBV1.3 were replaced by their counterparts from WHV. After HI with the WHV-HBV chimeric constructs in BALB/c mice, serum viral antigen, viral DNA (vDNA), and intrahepatic viral antigen expression were analyzed to evaluate the persistence of the chimeric genomes. Interestingly, we found that HI with three chimeric WHV-HBV genomes resulted in persistent antigenemia in mice. All of the persistent chimeric genomes contained the preC region and the part of the C region encoding the N-terminal 1-145 amino acids of the WHV genome. These results indicated that the preC region and the N-terminal part of the C region of the WHV genome may play a role in the persistent antigenemia. The chimeric WHV-HBV genomes were able to stably express viral antigens in the liver and could be further used to express hepadnaviral antigens to study their pathogenic potential.
Genome Sequence of Novel Human Parechovirus Type 17
Feb 24, 2017   Genome Announcements
Böttcher S, Obermeier PE, Diedrich S, Kaboré Y, D'Alfonso R, Pfister H, Kaiser R, Di Cristanziano V
Genome Sequence of Novel Human Parechovirus Type 17
Feb 24, 2017
Genome Announcements
Human parechoviruses (HPeV) circulate worldwide, causing a broad variety of symptoms, preferentially in early childhood. We report here the nearly complete genome sequence of a novel HPeV type, consisting of 7,062 nucleotides and encoding 2,179 amino acids. M36/CI/2014 was taxonomically classified as HPeV-17 by the picornavirus study group.Copyright © 2017 Böttcher et al.
Antiviral activity of peptide inhibitors derived from the protein E stem against Japanese encephalitis and Zika viruses
Feb 24, 2017   Antiviral Research
Chen L, Liu Y, Wang S, Sun J, Wang P, Xin Q, Zhang L, Xiao G, Wang W
Antiviral activity of peptide inhibitors derived from the protein E stem against Japanese encephalitis and Zika viruses
Feb 24, 2017
Antiviral Research
Japanese encephalitis virus (JEV) and Zika virus (ZIKV) are mosquito-borne viruses of the Flavivirus genus that cause viral encephalitis and congenital microcephaly, respectively, in humans, and thus present a risk to global public health. The envelope glycoprotein (E protein) of flaviviruses is a class II viral fusion protein that mediates host cell entry through a series of conformational changes, including association between the stem region and domain II leading to virion-target cell membrane fusion. In this study, peptides derived from the JEV E protein stem were investigated for their ability to block JEV and ZIKV infection. Peptides from stem helix 2 inhibit JEV infection with the 50% inhibitory concentration (ICCopyright © 2017. Published by Elsevier B.V.
Fair Reporting of Study Results
Feb 24, 2017   Clinical Microbiology And Infection : The Official Publication Of The European Society Of Clinical Microbiology And Infectious Diseases
Huttner A, Kaiser L
Fair Reporting of Study Results
Feb 24, 2017
Clinical Microbiology And Infection : The Official Publication Of The European Society Of Clinical Microbiology And Infectious Diseases
Corrigendum to 'Sinu virus, a novel and divergent orthomyxovirus related to members of the genus Thogotovirus isolated from mosquitoes in Colombia' [Virology 501 (2017) 166-175]
Feb 24, 2017   Virology
Contreras-Gutiérrez MA, Nunes MR, Guzman H, Uribe S, Suaza Vasco JD, Cardoso JF, Popov VL, Widen SG, Wood TG, Vasilakis N, Tesh RB
A polymorphism within the internal fusion loop of the Ebola virus glycoprotein modulates host cell entry
Feb 23, 2017   Journal Of Virology
Hoffmann M, Crone L, Dietzel E, Paijo J, González-Hernández M, Nehlmeier I, Kalinke U, Becker S, Pöhlmann S
A polymorphism within the internal fusion loop of the Ebola virus glycoprotein modulates host cell entry
Feb 23, 2017
Journal Of Virology
The large scale of the Ebola virus disease (EVD) outbreak in West Africa in 2013-2016 raised the question whether the host cell interactions of the responsible Ebola virus (EBOV) strain differed from those of other ebolaviruses. We previously reported that the glycoprotein (GP) of the virus circulating in West Africa in 2014 (EBOV2014) exhibited reduced ability to mediate entry into two non-human primate (NHP)-derived cell lines relative to the GP of EBOV1976. Here, we investigated the molecular determinants underlying the differential entry efficiency. We found that EBOV2014-GP-driven entry into diverse NHP-derived cell lines as well as human monocyte-derived macrophages and dendritic cells was reduced as compared to EBOV1976-GP, although entry into most human- and all bat-derived cell lines tested was comparable. Moreover, EBOV2014 replication in NHP but not human cells was diminished relative to EBOV1976, suggesting that reduced cell entry translated into reduced viral spread. Mutagenic analysis of EBOV2014-GP and EBOV1976-GP revealed that an amino acid polymorphism in the receptor-binding domain, A82V, modulated entry efficiency in a cell line-independent manner and did not account for the reduced EBOV2014-GP-driven entry into NHP cells. In contrast, polymorphism T544I, located in the internal fusion loop in the GP2 subunit, was found to be responsible for the entry phenotype. These results suggest that position 544 is an important determinant of EBOV infectivity for NHP- and certain human target cells.Copyright © 2017 American Society for Microbiology.
Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells
Feb 23, 2017   Proceedings Of The National Academy Of Sciences Of The United States Of America
Baldauf HM, Stegmann L, Schwarz SM, Ambiel I, Trotard M,   . . . . . .   , König R, Kim B, Emerman M, Fackler OT, Keppler OT
Vpx overcomes a SAMHD1-independent block to HIV reverse transcription that is specific to resting CD4 T cells
Feb 23, 2017
Proceedings Of The National Academy Of Sciences Of The United States Of America
Early after entry into monocytes, macrophages, dendritic cells, and resting CD4 T cells, HIV encounters a block, limiting reverse transcription (RT) of the incoming viral RNA genome. In this context, dNTP triphosphohydrolase SAM domain and HD domain-containing protein 1 (SAMHD1) has been identified as a restriction factor, lowering the concentration of dNTP substrates to limit RT. The accessory lentiviral protein X (Vpx) proteins from the major simian immunodeficiency virus of rhesus macaque, sooty mangabey, and HIV-2 (SIVsmm/SIVmac/HIV-2) lineage packaged into virions target SAMHD1 for proteasomal degradation, increase intracellular dNTP pools, and facilitate HIV cDNA synthesis. We find that virion-packaged Vpx proteins from a second SIV lineage, SIV of red-capped mangabeys or mandrills (SIVrcm/mnd-2), increased HIV infection in resting CD4 T cells, but not in macrophages, and, unexpectedly, acted in the absence of SAMHD1 degradation, dNTP pool elevation, or changes in SAMHD1 phosphorylation. Vpx rcm/mnd-2 virion incorporation resulted in a dramatic increase of HIV-1 RT intermediates and viral cDNA in infected resting CD4 T cells. These analyses also revealed a barrier limiting HIV-1 infection of resting CD4 T cells at the level of nuclear import. Single amino acid changes in the SAMHD1-degrading Vpx mac239 allowed it to enhance early postentry steps in a Vpx rcm/mnd-2-like fashion. Moreover, Vpx enhanced HIV-1 infection of SAMHD1-deficient resting CD4 T cells of a patient with Aicardi-Goutières syndrome. These results indicate that Vpx, in addition to SAMHD1, overcomes a previously unappreciated restriction for lentiviruses at the level of RT that acts independently of dNTP concentrations and is specific to resting CD4 T cells.
Anti-RNPC3 Antibodies as a Marker of Cancer-Associated Scleroderma
Feb 20, 2017   Arthritis & Rheumatology (Hoboken, N.J.)
Shah AA, Xu G, Rosen A, Hummers LK, Wigley FM, Elledge SJ, Casciola-Rosen L
Anti-RNPC3 Antibodies as a Marker of Cancer-Associated Scleroderma
Feb 20, 2017
Arthritis & Rheumatology (Hoboken, N.J.)
INTRODUCTION: Prior studies have demonstrated an increased risk of cancer-associated scleroderma in patients with RNA polymerase III (POL) autoantibodies and in patients negative for anti-centromere (CENP), anti-topoisomerase-1 (TOPO), and anti-POL antibodies (referred to as CENP/TOPO/POL (CTP)-Negative). In a recent study of 16 CTP-negative scleroderma patients with coincident cancer, we found that 25% had autoantibodies to RNPC3, a member of the minor spliceosome complex. In this investigation, we validated the relationship between anti-RNPC3 antibodies and cancer and examined the associated clinical phenotype in a large sample of scleroderma patients. METHODS: Scleroderma patients with cancer were assayed for CENP, TOPO, POL and RNPC3 autoantibodies. Disease characteristics and the cancer-scleroderma interval were compared across autoantibody groups. The relationship between autoantibody status and cancer-associated scleroderma was assessed by logistic regression. RESULTS: Of 318 patients with scleroderma and cancer, 70 (22.0%) were positive for anti-POL, 54 (17.0%) for anti-TOPO, and 96 (30.2%) for anti-CENP. Twelve patients (3.8% of overall group or 12.2% of CTP-negatives) were positive for anti-RNPC3. Patients with anti-RNPC3 had a short cancer-scleroderma interval (median 0.9 years). Relative to patients with anti-CENP, patients with anti-RNPC3 (OR 4.3; 95%CI 1.10-16.9; p=0.037) and anti-POL (OR 4.49; 95%CI 1.98-10.2; p4-fold increased risk of cancer within 2 years of scleroderma onset. Patients with anti-RNPC3 had severe restrictive lung and gastrointestinal disease, Raynaud's, and myopathy. CONCLUSION: Anti-RNPC3 autoantibodies associate with an increased risk of cancer at scleroderma onset, similar to POL autoantibodies. These data suggest the possibility of cancer-induced autoimmunity in this scleroderma subset. This article is protected by copyright. All rights reserved. © 2017, American College of Rheumatology.
ICTV Virus Taxonomy Profile: Flaviviridae
Feb 20, 2017   The Journal Of General Virology
Simmonds P, Becher P, Bukh J, Gould EA, Meyers G, Monath T, Muerhoff S, Pletnev A, Rico-Hesse R, Smith DB, Stapleton JT, Ictv Report Consortium
ICTV Virus Taxonomy Profile: Flaviviridae
Feb 20, 2017
The Journal Of General Virology
UNASSIGNED: The Flaviviridae is a family of small enveloped viruses with RNA genomes of 9000-13 000 bases. Most infect mammals and birds. Many flaviviruses are host-specific and pathogenic, such as hepatitis C virus in the genus Hepacivirus. The majority of known members in the genus Flavivirus are arthropod borne, and many are important human and veterinary pathogens (e.g. yellow fever virus, dengue virus). This is a summary of the current International Committee on Taxonomy of Viruses (ICTV) report on the taxonomy of the Flaviviridae, which is available at www.ictv.global/report/flaviviridae.
Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited
Feb 20, 2017   ACS Medicinal Chemistry Letters
Drakopoulos A, Tzitzoglaki C, Ma C, Freudenberger K, Hoffmann A, Hu Y, Gauglitz G, Schmidtke M, Wang J, Kolocouris A
Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited
Feb 20, 2017
ACS Medicinal Chemistry Letters
UNASSIGNED: Recent findings from solid state NMR (ssNMR) studies suggested that the (
Dendritic cells infected by Ad-sh-SOCS1 enhance cytokine-induced killer (CIK) cell immunotherapeutic efficacy in cervical cancer models
Feb 20, 2017   Cytotherapy
Zheng Y, Hu B, Xie S, Chen X, Hu Y, Chen W, Li S, Hu B
Dendritic cells infected by Ad-sh-SOCS1 enhance cytokine-induced killer (CIK) cell immunotherapeutic efficacy in cervical cancer models
Feb 20, 2017
Cytotherapy
BACKGROUND AIMS: Cervical cancer constitutes a major problem in women's health worldwide, but the efficacy of the standard therapy is unsatisfactory. Cytokine-induced killer (CIK) cells exhibit antitumor activity against a variety of malignancies in preclinical models and have proven safe and effective in clinical trials. However, current CIK therapy has limitations and needs to be improved to meet the clinical requirements. The aim of this study was to investigate whether suppressing the expression of cytokine signaling 1 (SOCS1) in dendritic cells (DCs) can shorten in vitro CIK culture time and improve its antitumor efficacy. METHODS: DCs were pre-cultured for 3 days before infected with adenovirus-mediated-SOCS1 short hairpin RNA (Ad-sh-SOCS1) and pulsed with CTL epitope peptides E7. The DCs infected by Ad-sh-SOCS1 (gmDCs) and CIKs were then co-cultured for 5 or 9 days, and CIK proliferation and antitumor activity were evaluated both in vitro and in vivo. RESULTS: Our data show that gmDCs significantly stimulated the expansion of co-cultured CIKs and increased the secretion of interferon-γ and interleukin-12. Moreover, gmDCs-activated CIKs showed higher cytotoxic activity against TC-1 cells expressing HPV16E6 and E7. Our in vivo study showed that the mice infused with gmDCs-activated CIKs on day 10 had an increased survival rate and prolonged survival time compared with the controls. CONCLUSIONS: Taken together, these results indicate that DCs modified by adenovirus-mediated SOCS1 silencing can promote CIKs expansion and enhance the efficacy of antitumor immunotherapy both in vitro and in vivo, which represents an effective therapeutic approach for cervical cancer and other tumors. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Rice grassy stunt virus p5 interacts with two protein components of the plant-specific CBL-CIPK Ca
Feb 18, 2017   Virus Genes
Xiong G, Liu X, Qiu P, Wu X, Du Z, Zhang J, Yang L, Wu Z
Rice grassy stunt virus p5 interacts with two protein components of the plant-specific CBL-CIPK Ca
Feb 18, 2017
Virus Genes
UNASSIGNED: Rice grassy stunt virus (RGSV) is a tenuivirus posing a threat to rice production in many South, Southeast, and East Asian countries. To date, no host factor interacting with RGSV has been reported. In this study, we screened a rice cDNA library with the GAL4-based yeast two-hybrid system using RGSV p5 as the bait. One of the candidate host factors interacting with RGSV p5 was found to be CBL-interacting protein kinase 25 (OsCIPK25), a member of the plant-specific CBL-CIPK Ca
Diversity, evolution and population dynamics of avian influenza viruses circulating in the live poultry markets in China
Feb 21, 2017   Virology
Chen LJ, Lin XD, Tian JH, Liao Y, Ying XH, Shao JW, Yu B, Guo JJ, Wang MR, Peng Y, Shi M, Holmes EC, Yang ZQ, Zhang YZ
Diversity, evolution and population dynamics of avian influenza viruses circulating in the live poultry markets in China
Feb 21, 2017
Virology
UNASSIGNED: Live poultry markets (LPMs) are an important source of novel avian influenza viruses (AIV). During 2015-2016 we surveyed AIV diversity in ten LPMs in Hubei, Zhejiang and Jiangxi provinces, China. A high diversity and prevalence of AIVs (totaling 12 subtypes) was observed in LPMs in these provinces. Strikingly, however, the subtypes discovered during 2015-2016 were markedly different to those reported by us in these same localities one year previously, suggesting a dynamic shift in viral genetic diversity over the course of a single year. Phylogenetic analyses revealed frequent reassortment, including between high and low pathogenic AIV subtypes and among those that circulate in domestic and wild birds. Notably, the novel H5N6 reassortant virus, which contains a set of H9N2-like internal genes, was prevalent in all three regions surveyed. Overall, these data highlight the profound changes in genetic diversity and in patterns of reassortment in those AIVs that circulate in LPMs. Copyright © 2017 Elsevier Inc. All rights reserved.
Identification of miRNA-mRNA crosstalk in CD4
Feb 22, 2017   Journal Of Translational Medicine
Liao Q, Wang J, Pei Z, Xu J, Zhang X
Identification of miRNA-mRNA crosstalk in CD4
Feb 22, 2017
Journal Of Translational Medicine
BACKGROUND: HIV-1-infected long-term nonprogressors (LTNPs) are characterized by infection with HIV-1 more than 7-10 years, but keeping high CD4 METHODS: To identify microRNAs (miRNAs) and their target genes related to distinct clinical outcomes in HIV-1 infection, we performed the integrative transcriptome analyses in two series GSE24022 and GSE6740 by GEO2R, R, TargetScan, miRDB, and Cytoscape softwares. The functional pathways of these differentially expressed miRNAs (DEMs) targeting genes were further analyzed with DAVID. RESULTS: We identified that 7 and 19 DEMs in CD4 CONCLUSIONS: Integrative transcriptome analyses showed that distinct transcriptional profiles in CD4
Antibody responses to Zika virus infections in flavivirus-endemic environments
Feb 23, 2017   Clinical And Vaccine Immunology : CVI
Keasey SL, Pugh CL, Jensen SM, Smith JL, Hontz RD, Durbin AP, Dudley DM, O'Connor DH, Ulrich RG
Antibody responses to Zika virus infections in flavivirus-endemic environments
Feb 23, 2017
Clinical And Vaccine Immunology : CVI
Zika virus (ZIKV) infections occur in areas where dengue (DENV), West Nile (WNV), yellow fever (YFV), and other viruses of the genus Copyright © 2017 American Society for Microbiology.
Spectroscopic, Polarographic, and Microcalorimetric Studies on Mitochondrial Dysfunction Induced by Ethanol
Feb 22, 2017   The Journal Of Membrane Biology
Ma L, Dong JX, Wu C, Li XY, Chen J, Zhang H, Liu Y
Spectroscopic, Polarographic, and Microcalorimetric Studies on Mitochondrial Dysfunction Induced by Ethanol
Feb 22, 2017
The Journal Of Membrane Biology
UNASSIGNED: Liver mitochondria are involved in several important life processes; mitochondrial dysfunction and disorders are implicated in several human diseases. Alcohol permeates all tissues of the body and exerts some intrinsic hepatotoxicity. In this work, our results demonstrated that ethanol caused a series of mitochondria permeability transition pore (MPTP) opening factors such as mitochondrial swelling, increased permeability of H
Development and application of nsp5-ELISA for the detection of antibody to infectious bronchitis virus
Feb 22, 2017   Journal Of Virological Methods
Lei J, Shi T, Sun D, Mo K, Yan Y, Jin Y, Liao M, Zhou J
Development and application of nsp5-ELISA for the detection of antibody to infectious bronchitis virus
Feb 22, 2017
Journal Of Virological Methods
UNASSIGNED: Infectious bronchitis virus (IBV) continues to be one of the most important poultry pathogens worldwide. The current commercially available enzyme-linked immunosorbent assay (ELISA) kits for IBV specific antibody detection are mostly based on the whole virion, and few serological tests based on nonstructural proteins of IBV have been developed. Herein, an alternative indirect ELISA for detection of IBV antibody was developed with IBV nonstructural protein 5 (nsp5) produced by Escherichia coli. Using an indirect immunofluorescence assay (IFA) and a commercial ELISA kit as reference, we optimized the nsp5-ELISA and determined its cut-off as 0.12. The diagnostic sensitivity (DSN), specificity (DSP) and accuracy of the nsp5-ELISA were 93.11%, 95.38% and 93.33%, respectively, compared with IFA in 660 field serum samples, and were 98.11%, 95.00% and 97.62%, respectively, compared with the commercial IBV ELISA kit (IDEXX) in 126 field sera samples. Furthermore, a time course of IBV specific antibody level detected by nsp5-ELISA following IBV infection and vaccination is consistent with that of IBV antibody detected by the commercial ELISA kit. The results presented in this study indicate that nsp5-ELISA has the potential to serve as a rapid, reliable and cost-effective method for IBV antibody detection. This study is the first to report the development of an nsp-based ELISA to detect an antibody to IBV. Copyright © 2017. Published by Elsevier B.V.
Detection and genome characterization of four novel bat hepadnaviruses and a hepevirus in China
Feb 22, 2017   Virology Journal
Wang B, Yang XL, Li W, Zhu Y, Ge XY, Zhang LB, Zhang YZ, Bock CT, Shi ZL
Detection and genome characterization of four novel bat hepadnaviruses and a hepevirus in China
Feb 22, 2017
Virology Journal
BACKGROUND: In recent years, novel hepadnaviruses, hepeviruses, hepatoviruses, and hepaciviruses have been discovered in various species of bat around the world, indicating that bats may act as natural reservoirs for these hepatitis viruses. In order to further assess the distribution of hepatitis viruses in bat populations in China, we tested the presence of these hepatitis viruses in our archived bat liver samples that originated from several bat species and various geographical regions in China. METHODS: A total of 78 bat liver samples (involving two families, five genera, and 17 species of bat) were examined using nested or heminested reverse transcription PCR (RT-PCR) with degenerate primers. Full-length genomic sequences of two virus strains were sequenced followed by phylogenetic analyses. RESULTS: Four samples were positive for hepadnavirus, only one was positive for hepevirus, and none of the samples were positive for hepatovirus or hepacivirus. The hepadnaviruses were discovered in the horseshoe bats, Rhinolophus sinicus and Rhinolophus affinis, and the hepevirus was found in the whiskered bat Myotis davidii. The full-length genomic sequences were determined for one of the two hepadnaviruses identified in R. sinicus (designated BtHBVRs3364) and the hepevirus (designated BtHEVMd2350). A sequence identity analysis indicated that BtHBVRs3364 had the highest degree of identity with a previously reported hepadnavirus from the roundleaf bat, Hipposideros pomona, from China, and BtHEVMd2350 had the highest degree of identity with a hepevirus found in the serotine bat, Eptesicus serotinus, from Germany, but it exhibited high levels of divergence at both the nucleotide and the amino acid levels. CONCLUSIONS: This is the first study to report that the Chinese horseshoe bat and the Chinese whiskered bat have been found to carry novel hepadnaviruses and a novel hepevirus, respectively. The discovery of BtHBVRs3364 further supports the significance of host switches evolution while opposing the co-evolutionary theory associated with hepadnaviruses. According to the latest criterion of the International Committee on Taxonomy of Viruses (ICTV), we hypothesize that BtHEVMd2350 represents an independent genotype within the species Orthohepevirus D of the family Hepeviridae.
Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response
Feb 18, 2017   Proceedings Of The National Academy Of Sciences Of The United States Of America
Kozaki T, Komano J, Kanbayashi D, Takahama M, Misawa T, Satoh T, Takeuchi O, Kawai T, Shimizu S, Matsuura Y, Akira S, Saitoh T
Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response
Feb 18, 2017
Proceedings Of The National Academy Of Sciences Of The United States Of America
UNASSIGNED: The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation. TIPARP typically localizes in the nucleus, but it accumulates in the cytoplasm after SINV infection, allowing targeting of cytoplasmic SINV RNA. Redistribution of TIPARP is induced by reactive oxygen species (ROS)-dependent oxidization of the nuclear pore that affects cytoplasmic-nuclear transport. BCL2-associated X protein (BAX) and BCL2 antagonist/killer 1 (BAK1), B-cell leukemia/lymphoma 2 (BCL2) family members, mediate mitochondrial damage to generate ROS after SINV infection. Thus, TIPARP is a viral RNA-sensing PRR that mediates antiviral responses triggered by BAX- and BAK1-dependent mitochondrial damage.

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