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https://www.readbyqxmd.com/read/28733598/role-of-hdac9-foxo1-axis-in-the-transcriptional-program-associated-with-hepatic-gluconeogenesis
#1
Jizheng Chen, Zhilei Zhang, Ning Wang, Min Guo, Xiumei Chi, Yu Pan, Jing Jiang, Junqi Niu, Sulaiman Ksimu, John Zhong Li, Xinwen Chen, Qian Wang
Histone deacetylase 9 (HDAC9) regulates hepatic gluconeogenesis by deacetylating Forkhead box O 1 (FoxO1). HDAC9 upregulation is involved in hepatitis C virus (HCV)-associated exaggerated gluconeogenesis. Herein, we found in addition to FoxO1, HDAC9 also regulates other gluconeogenic transcription factors, including peroxisomeproliferator-activated receptor-γ coactivator-1α (PGC-1α), cyclic AMP-responsive element-binding protein (CREB), and glucocorticoid receptor (GR). Unlike FoxO1, which is regulated by post-translational modification responses to HDAC9, HDAC9 regulates PGC-1α, CREB and GR by altering gene expression...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733129/endocannabinoids-exert-cb1-receptor-mediated-neuroprotective-effects-in-models-of-neuronal-damage-induced-by-hiv-1-tat-protein
#2
Changqing Xu, Douglas J Hermes, Blessing Nwanguma, Ian R Jacobs, Kenneth Mackie, Somnath Mukhopadhyay, Aron H Lichtman, Bogna Ignatowska-Jankowska, Sylvia Fitting
In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND). Endocannabinoids (eCBs) elicit neuroprotective and anti-inflammatory actions in several central nervous system (CNS) disease models, but their effects in HAND remain unknown. HIV-1 does not infect neurons, but produces viral toxins, such as transactivator of transcription (Tat), that disrupt neuronal calcium equilibrium and give rise to synaptodendritic injuries and cell death, the former being highly correlated with HAND...
July 18, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28732227/atm-supports-gammaherpesvirus-replication-by-attenuating-type-i-interferon-pathway
#3
Eric J Darrah, Kyle P Stoltz, Mitchell Ledwith, Vera L Tarakanova
Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages...
July 18, 2017: Virology
https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#4
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28732051/cd4-is-expressed-on-a-heterogeneous-subset-of-hematopoietic-progenitors-which-persistently-harbor-cxcr4-and-ccr5-tropic-hiv-proviral-genomes-in-vivo
#5
Nadia T Sebastian, Thomas D Zaikos, Valeri Terry, Frances Taschuk, Lucy A McNamara, Adewunmi Onafuwa-Nuga, Ryan Yucha, Robert A J Signer, James Riddell, Dale Bixby, Norman Markowitz, Sean J Morrison, Kathleen L Collins
Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28730979/adsorption-of-staphylococcus-viruses-s13-and-s24-1-on-staphylococcus-aureus-strains-with-different-glycosidic-linkage-patterns-of-wall-teichoic-acids
#6
Jumpei Uchiyama, Maya Taniguchi, Kenji Kurokawa, Iyo Takemura-Uchiyama, Takako Ujihara, Hidekatsu Shimakura, Yoshihiko Sakaguchi, Hironobu Murakami, Masahiro Sakaguchi, Shigenobu Matsuzaki
The group of phages belonging to the family Podoviridae, genus P68virus, including Staphylococcus viruses S13' and S24-1, are important because of their benefits in phage therapy against Staphylococcus aureus infections. The O-glycosidic linkage patterns of wall teichoic acids (WTAs) in S. aureus cell walls seem to be important for adsorption of this phage group. In this study, the adsorption of Staphylococcus viruses S13' and S24-1 to S. aureus was examined using strains with modified WTA glycosidic linkage patterns...
July 21, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28730878/investigational-drugs-in-development-for-hepatitis-d
#7
Mario Rizzetto
Treatment of chronic hepatitis D still relies on Interferon. To improve efficacy, new therapeutic strategies are in development which aim to deprive the Hepatitis D Virus (HDV) of functions of the Hepatitis B Virus and of the host required for its life-cycle. Areas covered: The therapeutic options are; 1) The inhibition of the farnesylation of the large HD-protein permissive of virion assembly with Lonafarnib, 2) The blocking of HBsAg entry into cells with Myrcludex B via the inhibition of the Sodium Taurocholate Cotransporting Receptor, to prevent the spreading of HDV to uninfected hepatocytes, 3) The reduction of subviral HBsAg particles by REP 2139, leading to diminished virion morphogenesis ...
July 21, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28729706/sudan-ebolavirus-long-recovered-survivors-produce-gp-specific-abs-that-are-of-the-igg1-subclass-and-preferentially-bind-fc%C3%AE-ri
#8
Olga Radinsky, Avishay Edri, Michael Brusilovsky, Shlomit Fedida-Metula, Ariel Sobarzo, Orly Gershoni-Yahalom, Julius Lutwama, John Dye, Leslie Lobel, Angel Porgador
Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729347/lethal-avian-influenza-a-h5n1-virus-induces-ataxic-breathing-in-mice-with-apoptosis-of-pre-botzinger-complex-neurons-expressing-neurokinin-1-receptor
#9
Jianguo Zhuang, Na Zang, Chunyan Ye, Fadi Xu
BACKGROUND: Lethal influenza A (H5N1) induces respiratory failure in humans. Although it also causes death at 7 day postinfection (dpi) in mice, the development of the respiratory failure and the viral impact on pre-Botzinger complex (PBC) neurons expressing neurokinin 1 receptor (NK1R), the respiratory rhythm-generator, have not been explored. METHODS: Body temperature, weight, ventilation, arterial blood pH and gases were measured at 0, 2, 4, and 6 dpi in control, lethal HK483 and non-lethal HK486 viral infected mice...
July 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28727829/functional-differentiation-and-spatial-temporal-co-expression-networks-of-the-nbs-encoding-gene-family-in-jilin-ginseng-panax-ginseng-c-a-meyer
#10
Rui Yin, Mingzhu Zhao, Kangyu Wang, Yanping Lin, Yanfang Wang, Chunyu Sun, Yi Wang, Meiping Zhang
Ginseng, Panax ginseng C.A. Meyer, is one of the most important medicinal plants for human health and medicine. It has been documented that over 80% of genes conferring resistance to bacteria, viruses, fungi and nematodes are contributed by the nucleotide binding site (NBS)-encoding gene family. Therefore, identification and characterization of NBS genes expressed in ginseng are paramount to its genetic improvement and breeding. However, little is known about the NBS-encoding genes in ginseng. Here we report genome-wide identification and systems analysis of the NBS genes actively expressed in ginseng (PgNBS genes)...
2017: PloS One
https://www.readbyqxmd.com/read/28727685/erbb4-signaling-in-dopaminergic-axonal-projections-increases-extracellular-dopamine-levels-and-regulates-spatial-working-memory-behaviors
#11
M Skirzewski, I Karavanova, A Shamir, L Erben, J Garcia-Olivares, J H Shin, D Vullhorst, V A Alvarez, S G Amara, A Buonanno
Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28726743/the-effect-of-n-terminal-cyclization-on-the-function-of-the-hiv-entry-inhibitor-5p12-rantes
#12
Anna F Nguyen, Megan S Schill, Mike Jian, Patricia J LiWang
Despite effective treatment for those living with Human Immunodeficiency Virus (HIV), there are still two million new infections each year. Protein-based HIV entry inhibitors, being highly effective and specific, could be used to protect people from initial infection. One of the most promising of these for clinical use is 5P12-RANTES, a variant of the chemokine RANTES/CCL5. The N-terminal amino acid of 5P12-RANTES is glutamine (Gln; called Q0), a residue that is prone to spontaneous cyclization when at the N-terminus of a protein...
July 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28725225/antiviral-functions-of-human-immunodeficiency-virus-type-1-hiv-1-specific-igg-antibodies-effects-of-antiretroviral-therapy-and-implications-for-therapeutic-hiv-1-vaccine-design
#13
REVIEW
Martyn A French, M Christian Tjiam, Laila N Abudulai, Sonia Fernandez
Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting "protective" HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28725108/identification-of-the-linear-ligand-epitope-on-classical-swine-fever-virus-that-interacts-with-porcine-kidney-15-cells
#14
Yin Mei, Feng Yue, Hong-Mei Ning, Juan-Juan Zhou, Xuan-Nian Wang
Binding of the viral ligand to a specific receptor is the first step of virus entry into target cells. The envelope proteins E(rns), E1, and E2 of classical swine fever virus (CSFV) are involved in the interaction with host cell receptors to mediate CSFV infection. The aim of this investigation was to identify epitopes that bind to porcine kidney (PK)-15 cells to prevent CSFV infection. Ten peptides representing E(rns), E1, and E2 were synthesized. Immunohistochemical study showed that the SE24 peptide, which is derived from the E2 amino acid sequence, could effectively bind to PK-15 cells...
July 2017: Canadian Journal of Veterinary Research, Revue Canadienne de Recherche Vétérinaire
https://www.readbyqxmd.com/read/28724955/mushroom-lectin-overcomes-hepatitis-b-virus-tolerance-via-tlr6-signaling
#15
Meina He, Dan Su, Qinghong Liu, Wenjuan Gao, Youmin Kang
Currently, chronic hepatitis B virus (HBV) infection remains a serious public health problem in the world. Recombinant HBV vaccine, as a preventive strategy against HBV infection, generates high antibody level, but it is not effective to activate innate and cellular immunity for chronic HBV infection therapy. Lectins from mushroom are natural and active proteins which have been shown important biological functions. However, little is known about the immunological mechanism engaged by mushroom lectins. Here we report that, lectin from Pleurotus ostreatus (POL) stimulated innate response by activating Toll-like receptor 6 signal pathway of dendritic cells...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724801/tcr-ligand-dissociation-rate-is-a-robust-and-stable-biomarker-of-cd8-t-cell-potency
#16
Mathilde Allard, Barbara Couturaud, Laura Carretero-Iglesia, Minh Ngoc Duong, Julien Schmidt, Gwennaëlle C Monnot, Pedro Romero, Daniel E Speiser, Michael Hebeisen, Nathalie Rufer
Despite influencing many aspects of T cell biology, the kinetics of T cell receptor (TCR) binding to peptide-major histocompatibility molecules (pMHC) remain infrequently determined in patient monitoring or for adoptive T cell therapy. Using specifically designed reversible fluorescent pMHC multimeric complexes, we performed a comprehensive study of TCR-pMHC off-rates combined with various functional assays on large libraries of self/tumor- and virus-specific CD8+ T cell clones from melanoma patients and healthy donors...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724773/nkp46-recognizes-the-sigma1-protein-of-reovirus-implications-for-reovirus-based-cancer-therapy
#17
Yotam Bar-On, Yoav Charpak-Amikam, Ariella Glasner, Batya Isaacson, Alexandra Duev-Cohen, Pinchas Tsukerman, Alexander Varvak, Michal Mandelboim, Ofer Mandelboim
The recent approval of onclolytic virus for therapy of melanoma patients has increased the need for precise evaluation of the mechanisms by which oncolytic viruses affect tumor growth. Here we show that the human NK activating receptor, NKp46, and its mouse orthologous protein, NCR1, recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify NKp46/NCR1 binding sites to sigma1 and show that sigma1 binding by NKp46/NCR1 leads to NK cell activation in vitro Finally, we demonstrate that NCR1 activation is essential for reovirus-based therapy in vivo Collectively, we identified sigma1 as a novel ligand for NKp46/NCR1 and demonstrated that NKp46/NCR1 is needed for both clearance of reovirus infections and reovirus-based tumor therapy...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724770/rgs-cam-detects-and-counteracts-viral-rna-silencing-suppressors-in-plant-immune-priming
#18
Eun Jin Jeon, Kazuki Tadamura, Taiki Murakami, Jun-Ichi Inaba, Bo Min Kim, Masako Sato, Go Atsumi, Kazuyuki Kuchitsu, Chikara Masuta, Kenji S Nakahara
Primary infection of a plant with a pathogen that causes high accumulation of salicylic acid in the plant typically via a hypersensitive response confers enhanced resistance against secondary infection with a broad spectrum of pathogens, including viruses. This phenomenon is called systemic acquired resistance (SAR), which is a plant-priming for adaption to repeated biotic stress. However, the molecular mechanisms of SAR-mediated enhanced inhibition, especially of virus infection, remain unclear. Here, we show that SAR against cucumber mosaic virus (CMV) in tobacco plants (Nicotiana tabacum) involves a calmodulin-like protein, rgs-CaM...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724768/synthetic-tlr4-and-tlr7-ligands-work-additively-via-myd88-to-induce-protective-antiviral-immunity-in-mice
#19
Peter H Goff, Tomoko Hayashi, Wenqian He, Shiyin Yao, Howard B Cottam, Gene S Tan, Brian Crain, Florian Krammer, Karen Messer, Minya Pu, Dennis A Carson, Peter Palese, Maripat Corr
We have previously demonstrated that the combination of synthetic small molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity protective against influenza viruses in homologous, heterologous and heterosubtypic murine challenge models. Combining TLR4 and TLR7 ligands balances Th1/Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function in vivo via their known receptors with negligible off-target effects to induce protective immunity...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724766/a-unique-t-cell-receptor-amino-acid-sequence-selected-by-htlv-i-tax301-309-specific-cytotoxic-t-cells-in-hla-a24-02-asymptomatic-carriers-and-adult-t-cell-leukemia-lymphoma-patients
#20
Yuko Ishihara, Yukie Tanaka, Seiichiro Kobayashi, Koji Kawamura, Hideki Nakasone, Ayumi Gomyo, Jin Hayakawa, Masaharu Tamaki, Yu Akahoshi, Naonori Harada, Machiko Kusuda, Kazuaki Kameda, Tomotaka Ugai, Hidenori Wada, Kana Sakamoto, Miki Sato, Kiriko Terasako-Saito, Misato Kikuchi, Shun-Ichi Kimura, Aki Tanihara, Shinichi Kako, Kaoru Uchimaru, Yoshinobu Kanda
We previously reported that the T-cell receptor (TCR) repertoire of HTLV-I Tax301-309-specific CD8(+) cytotoxic T-cells (Tax-CTLs) was highly restricted and a particular amino acid sequence motif, "PDR", was conserved among HLA-A*24:02(+) ATL patients who have undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR+CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-I. On the other hand, the TCR repertoires in Tax-CTL of asymptomatic HTLV-I carriers (ACs) remain unclear...
July 19, 2017: Journal of Virology
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