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https://www.readbyqxmd.com/read/28202752/human-herpesvirus-6a-hhv-6a-exhibits-restrictive-propagation-with-limited-activation-of-pkr-eif2%C3%AE-stress-pathway
#1
Eyal Sharon, Niza Frenkel
The eIF2α protein plays a critical role in the regulation of translation. The production of dsRNA during viral replication can activate protein kinase R (PKR) which phosphorylates the eIF2α, leading to inhibition of the initial step of translation. Many viruses have evolved gene products targeting PKR-eIF2a pathway, indicating its importance in antiviral defense. In the present study we focus on alternations of PKR-eIF2a pathway along HHV-6A infection while monitoring viral gene expression and infectious viral yields...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28186978/combination-antiretroviral-therapy-cart-restores-hiv-1-infection-mediated-impairment-of-jak-stat-signaling-pathway
#2
Man-Qing Liu, Min Zhao, Wen-Hua Kong, Li Tang, Fang Wang, Ze-Rong Zhu, Xia Wang, Hong-Yan Qiu, Dun-Jin Zhou, Xu Wang, Wen-Zhe Ho, Wang Zhou
JAK-STAT signaling pathway has a crucial role in host innate immunity against viral infections, including HIV-1. We therefore examined the impact of HIV-1 infection and combination antiretroviral therapy (cART) on JAK-STAT signaling pathway. Compared to age-matched healthy donors (n = 18), HIV-1-infected subjects (n = 18) prior to cART had significantly lower expression of toll-like receptors (TLR-1/4/6/7/8/9), the IFN regulatory factors (IRF-3/7/9), and the antiviral factors (OAS-1, MxA, A3G, PKR, and Tetherin)...
February 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28167698/adar1-and-pact-contribute-to-efficient-translation-of-transcripts-containing-hiv-1-trans-activating-response-tar-element
#3
Evelyn Chukwurah, Indhira Handy, Rekha C Patel
Human immunodeficiency virus type 1 (HIV-1) has evolved various measures to counter the host cell's innate antiviral response during the course of infection. Interferon (IFN)-stimulated gene products are produced following HIV-1 infection to limit viral replication, but viral proteins and RNAs counteract their effect. One such mechanism is specifically directed against the IFN-induced Protein Kinase R (PKR), which is centrally important to the cellular antiviral response. In the presence of viral RNAs, PKR is activated and phosphorylates the translation initiation factor, eIF2α...
February 6, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28158275/early-endonuclease-mediated-evasion-of-rna-sensing-ensures-efficient-coronavirus-replication
#4
Eveline Kindler, Cristina Gil-Cruz, Julia Spanier, Yize Li, Jochen Wilhelm, Huib H Rabouw, Roland Züst, Mihyun Hwang, Philip V'kovski, Hanspeter Stalder, Sabrina Marti, Matthias Habjan, Luisa Cervantes-Barragan, Ruth Elliot, Nadja Karl, Christina Gaughan, Frank J M van Kuppeveld, Robert H Silverman, Markus Keller, Burkhard Ludewig, Cornelia C Bergmann, John Ziebuhr, Susan R Weiss, Ulrich Kalinke, Volker Thiel
Coronaviruses are of veterinary and medical importance and include highly pathogenic zoonotic viruses, such as SARS-CoV and MERS-CoV. They are known to efficiently evade early innate immune responses, manifesting in almost negligible expression of type-I interferons (IFN-I). This evasion strategy suggests an evolutionary conserved viral function that has evolved to prevent RNA-based sensing of infection in vertebrate hosts. Here we show that the coronavirus endonuclease (EndoU) activity is key to prevent early induction of double-stranded RNA (dsRNA) host cell responses...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28157174/myxoma%C3%A2-virus%C3%A2-dsrna%C3%A2-binding%C3%A2-protein%C3%A2-m029%C3%A2-inhibits%C3%A2-the%C3%A2-type%C3%A2-i%C3%A2-ifn-induced%C3%A2-antiviral%C3%A2-state%C3%A2-in%C3%A2-a%C3%A2-highly%C3%A2-species-specific%C3%A2-fashion
#5
Masmudur M Rahman, Grant McFadden
Myxoma virus (MYXV) is Leporipoxvirus that possesses a specific rabbit-restricted host tropism but exhibits a much broader  cellular host range in cultured cells. MYXV is able to efficiently  block all aspects of the type I interferon (IFN)-induced  antiviral  state  in rabbit cells, partially in  human  cells  and  very  poorly  in  mouse  cells.  The mechanism(s) of this species-specific inhibition of  type I IFN-induced antiviral state is not well understood...
February 2, 2017: Viruses
https://www.readbyqxmd.com/read/28143523/immune-and-biochemical-responses-in-skin-differ-between-bovine-hosts-genetically-susceptible-and-resistant-to-the-cattle-tick-rhipicephalus-microplus
#6
Alessandra Mara Franzin, Sandra Regina Maruyama, Gustavo Rocha Garcia, Rosane Pereira Oliveira, José Marcos Chaves Ribeiro, Richard Bishop, Antônio Augusto Mendes Maia, Daniela Dantas Moré, Beatriz Rossetti Ferreira, Isabel Kinney Ferreira de Miranda Santos
BACKGROUND: Ticks attach to and penetrate their hosts' skin and inactivate multiple components of host responses in order to acquire a blood meal. Infestation loads with the cattle tick, Rhipicephalus microplus, are heritable: some breeds carry high loads of reproductively successful ticks, whereas in others, few ticks feed and reproduce efficiently. METHODS: In order to elucidate the mechanisms that result in the different outcomes of infestations with cattle ticks, we examined global gene expression and inflammation induced by tick bites in skins from one resistant and one susceptible breed of cattle that underwent primary infestations with larvae and nymphs of R...
January 31, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28138020/the-type-ii-secretion-system-of-legionella-pneumophila-dampens-the-myd88-and-tlr2-signaling-pathway-in-infected-human-macrophages
#7
Celeste A Mallama, Kessler McCoy-Simandle, Nicholas P Cianciotto
Previously, we reported that mutants of L. pneumophila lacking a type II secretion (T2S) system elicit higher levels of cytokines (e.g., IL-6) following infection of U937 cells, a human macrophage-like cell line. We now show that this effect of T2S is also manifest upon infection of human THP-1 cell macrophages and peripheral blood monocytes but does not occur during infection of murine macrophages. Supporting the hypothesis that T2S acts to dampen the triggering of an innate immune response, we observed that the mitogen-activated protein kinase (MAPK) and nuclear transcription factor kappa-B (NF-κB) pathways are more highly stimulated upon infection with the T2S mutant compared to wild-type...
January 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28122984/parvovirus-expresses-a-small-noncoding-rna-that-plays-an-essential-role-in-virus-replication
#8
Zekun Wang, Weiran Shen, Fang Cheng, Xuefeng Deng, John F Engelhardt, Ziying Yan, Jianming Qiu
: Human bocavirus 1 (HBoV1) belongs to species Primate bocaparvovirus of the genus Bocaparvovirus of the Parvoviridae family. HBoV1 causes acute respiratory tract infections in young children and has a selective tropism for the apical surface of well-differentiated human airway epithelia (HAE). In this study, we identify an additional HBoV1 gene, bocavirus-transcribed small non-coding RNA (BocaSR) within the 3' non-coding region (nt 5199-5338) of the viral genome of positive sense. BocaSR is transcribed by RNA polymerase III (Pol III) from an intragenic promoter at similar levels to that of the capsid protein-coding mRNA and is essential for replication of the viral DNA in both transfected HEK293 and infected HAE cells...
January 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28112215/zebularine-upregulates-expression-of-cyp-genes-through-inhibition-of-dnmt1-and-pkr-in-hepg2-cells
#9
Kazuaki Nakamura, Kazuko Aizawa, Kyaw Htet Aung, Junji Yamauchi, Akito Tanoue
Drug-induced hepatotoxicity is one of the major reasons cited for drug withdrawal. Therefore, it is of extreme importance to detect human hepatotoxic candidates as early as possible during the drug development process. In this study, we aimed to enhance hepatocyte functions such as CYP gene expression in HepG2 cells, one of the most extensively used cell lines in evaluating hepatotoxicity of chemicals and drugs. We found that zebularine, a potent inhibitor of DNA methylation, remarkably upregulates the expression of CYP genes in HepG2 cells...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#10
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28102839/foot-and-mouth-disease-virus-infection-suppresses-autophagy-and-nf-%C3%B0%C2%BAb-antiviral-responses-via-degradation-of-atg5-atg12-by-3c-pro
#11
Xuxu Fan, Shichong Han, Dan Yan, Yuan Gao, Yanquan Wei, Xiangtao Liu, Ying Liao, Huichen Guo, Shiqi Sun
Autophagy-related protein ATG5-ATG12 is an essential complex for the autophagophore elongation in autophagy, which has been reported to be involved in foot-and-mouth disease virus (FMDV) replication. Previous reports show that ATG5-ATG12 positively or negatively regulates type I interferon (IFN-α/β) pathway during virus infection. In this study, we found that FMDV infection rapidly induced LC3 lipidation and GFP-LC3 subcellular redistribution at the early infection stage in PK-15 cells. Along with infection time course to 2-5 h...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28100675/protein-synthesis-inhibition-and-gadd34-control-ifn-%C3%AE-heterogeneous-expression-in-response-to%C3%A2-dsrna
#12
Alexandre Dalet, Rafael J Argüello, Alexis Combes, Lionel Spinelli, Sebastien Jaeger, Mathieu Fallet, Thien-Phong Vu Manh, Andreia Mendes, Jessica Perego, Marisa Reverendo, Voahirana Camosseto, Marc Dalod, Tobias Weil, Manuel A Santos, Evelina Gatti, Philippe Pierre
In innate immune responses, induction of type-I interferons (IFNs) prevents virus spreading while viral replication is delayed by protein synthesis inhibition. We asked how cells perform these apparently contradictory activities. Using single fibroblast monitoring by flow cytometry and mathematical modeling, we demonstrate that type-I IFN production is linked to cell's ability to enter dsRNA-activated PKR-dependent translational arrest and then overcome this inhibition by decreasing eIF2α phosphorylation through phosphatase 1c cofactor GADD34 (Ppp1r15a) expression...
January 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28070110/melatonin-suppresses-methamphetamine-triggered-endoplasmic-reticulum-stress-in-c6-cells-glioma-cell-lines
#13
Wanida Tungkum, Pichaya Jumnongprakhon, Chainarong Tocharus, Piyarat Govitrapong, Jiraporn Tocharus
Methamphetamine (METH) is a neurotoxic drug that causes brain damage by inducing neuronal and glial cell death together with glial cell hyperactivity-mediated progressive neurodegeneration. Previous studies have shown that METH induced glial cell hyperactivity and death via oxidative stress, the inflammatory response, and endoplasmic reticulum stress (ER stress) mechanisms, and melatonin could reverse these effects. However, the exact mechanism of the protective role of melatonin in METH-mediated ER stress has not been understood...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28069888/human-non-coding-rna-886-nc886-adopts-two-structurally-distinct-conformers-that-are-functionally-opposing-regulators-of-pkr
#14
Brenda M Calderon, Graeme L Conn
The double-stranded RNA (dsRNA)-activated protein kinase (PKR) senses dsRNA produced during viral infection and halts cellular protein synthesis to block viral replication. How basal PKR activity is controlled in the absence of infection was unclear until the recent identification of a potential endogenous regulator, the cellular non-coding RNA 886 (nc886). However, nc886 adopts two distinct conformations for which the structural details and potential functional differences remain unclear. Here, we isolated and separately dissected the function of form of nc886 to more clearly define the molecular mechanism of nc886-mediated PKR inhibition...
January 9, 2017: RNA
https://www.readbyqxmd.com/read/28069423/identification-and-characterization-of-pyrokinin-and-capa-peptides-and-corresponding-gpcrs-from-spotted-wing-drosophila-drosophila-suzukii
#15
Man-Yeon Choi, Seung-Joon Ahn, A Young Kim, Youngho Koh
The family of FXPRLamide peptides serves as a major insect hormone. It is characterized by a core active amino acid sequence conserved at the C-terminal ends, and provides various physiological roles across the Insecta. In this study we identified and characterized pyrokinin (PK) and Capa cDNAs encoding two FXPRLamide peptides, pyrokinin and CAPA-DH (diapause hormone), and two corresponding G-protein-coupled receptors (GPCRs) from spotted wing drosophila (SWD), Drosophila suzukii. Expressions of PK and CAPA mRNAs were differentially observed during all life stages except the embryo, and the detection of CAPA transcription was relatively strong compared with the PK gene in SWD...
January 6, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28062005/gga-mir-2127-downregulates-the-translation-of-chicken-p53-and-attenuates-chp53-mediated-innate-immune-response-against-ibdv-infection
#16
Wei Ouyang, Yong-Shan Wang, Kai Meng, Qun-Xing Pan, Xiao-Li Wang, Xing-Xia Xia, Yu-Mei Zhu, Zhen-Wei Bi, Hai-Bin Zhang, Kai Luo
Infectious bursal disease (IBD) is characterized by the immune suppression of infected birds. The molecular mechanism by which IBD virus (IBDV) suppresses the host immune system remains to be elucidated. The tumor suppressor protein p53 can inhibit the replication of various viruses, but its effect on IBDV remains unknown. This study established an in vitro infection model based on DF-1 cells (chicken embryo fibroblast cell line) to investigate the antiviral effects of chicken p53 (chp53) on IBDV infection...
January 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28061446/%C3%AE-40p53-is-involved-in-the-inactivation-of-autophagy-and-contributes-to-inhibition-of-cell-death-in-hct116-%C3%AE-40p53-cells
#17
Yunjin Zang, Ying Shi, Kai Liu, Luxin Qiao, Xianghua Guo, Dexi Chen
Δ40p53 is an isoform of wild-type p53 (wtp53). Here, we assessed whether Δ40p53 has the same functions as wild-type p53 in the regulation of cell death and autophagy. First, we used HCT116 (p53+/+) and H1299 (p53-free) cells to produce two cell lines (HCT116-Δ40p53 and H1299-Δ40p53) that express exogenous Δ40p53 but not wtp53. By using these cell lines, we determined that Δ40p53 inhibited starvation-induced autophagy, as does wtp53. This inhibition arises from both Δ40p53 and wtp53 having 3'-5' exonuclease activity, which reduces the levels of double-stranded RNA (dsRNA) and then inhibits PKR/eIF2α-induced autophagy in cells exposed to starvation...
January 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28017918/effects-of-ketamine-administration-on-mtor-and-reticulum-stress-signaling-pathways-in-the-brain-after-the-infusion-of-rapamycin-into-prefrontal-cortex
#18
Helena M Abelaira, Gislaine Z Réus, Zuleide M Ignácio, Maria Augusta B Dos Santos, Airam B de Moura, Danyela Matos, Júlia P Demo, Júlia B I da Silva, Monique Michels, Mariane Abatti, Beatriz Sonai, Felipe Dal Pizzol, André F Carvalho, João Quevedo
Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC...
December 3, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28011649/newcastle-disease-virus-induces-stable-formation-of-bona-fide-stress-granules-to-facilitate-viral-replication-through-manipulating-host-protein-translation
#19
Yingjie Sun, Luna Dong, Shengqing Yu, Xiaoxu Wang, Hang Zheng, Pin Zhang, Chunchun Meng, Yuan Zhan, Lei Tan, Cuiping Song, Xusheng Qiu, Guijun Wang, Ying Liao, Chan Ding
Mammalian cells respond to various environmental stressors to form stress granules (SGs) by arresting cytoplasmic mRNA, protein translation element, and RNA binding proteins. Virus-induced SGs function in different ways, depending on the species of virus; however, the mechanism of SG regulation of virus replication is not well understood. In this study, Newcastle disease virus (NDV) triggered stable formation of bona fide SGs on HeLa cells through activating the protein kinase R (PKR)/eIF2α pathway. NDV-induced SGs contained classic SG markers T-cell internal antigen (TIA)-1, Ras GTPase-activating protein-binding protein (G3BP)-1, eukaryotic initiation factors, and small ribosomal subunit, which could be disassembled in the presence of cycloheximide...
December 23, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28008894/the-specific-protein-kinase-r-pkr-inhibitor-c16-protects-neonatal-hypoxia-ischemia-brain-damages-by-inhibiting-neuroinflammation-in-a-neonatal-rat-model
#20
Jinglei Xiao, Yongchang Tan, Yinjiao Li, Yan Luo
BACKGROUND Brain injuries induced by hypoxia-ischemia in neonates contribute to increased mortality and lifelong neurological dysfunction. The specific PKR inhibitor C16 has been previously demonstrated to exert a neuroprotective role in adult brain injuries. However, there is no recent study available concerning its protective role in hypoxia-ischemia-induced immature brain damage. Therefore, we investigated whether C16 protects against neonatal hypoxia-ischemia injuries in a neonatal rat model. MATERIAL AND METHODS Postnatal day 7 (P7) rats were used to establish classical hypoxia-ischemia animal models, and C16 postconditioning with 100 ug/kg was performed immediately after hypoxia...
December 23, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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