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https://www.readbyqxmd.com/read/28420742/synergistic-internal-ribosome-entry-site-microrna-based-approach-for-flavivirus-attenuation-and-live-vaccine-development
#1
Konstantin A Tsetsarkin, Guangping Liu, Evgeniya Volkova, Alexander G Pletnev
The recent emergence of Zika virus underscores the need for new strategies for a rapid development of safe flavivirus vaccines. Using another flavivirus (Langat virus [LGTV]) that belongs to the group of tick-borne flaviviruses as a model, we describe a dual strategy for virus attenuation which synergistically accesses the specificity of microRNA (miRNA) genome targeting and the effectiveness of internal ribosome entry site (IRES) insertion. To increase the stability and immunogenicity of bicistronic LGTVs, we developed a novel approach in which the capsid (C) protein gene was relocated into the 3' noncoding region (NCR) and expressed under translational control from an IRES...
April 18, 2017: MBio
https://www.readbyqxmd.com/read/28420741/new-mechanism-by-which-human-cytomegalovirus-micrornas-negate-the-proinflammatory-response-to-infection
#2
Andrew D Yurochko
Viruses have evolved many novel mechanisms to promote infection and to mitigate the host cell response to that infection. In the article by M. H. Hancock et al. (mBio 8:e00109-17, 2017, https://doi.org/10.1128/mBio.00109-17), the authors describe a new mechanism by which human cytomegalovirus (HCMV) microRNAs (miRNAs; miR-US5-1 and miR-UL112-3p) negate the proinflammatory response to infection. The authors document that these two viral miRNAs downregulate the NF-κB response through direct targeting of the IKKα and IKKβ mRNAs, which in turn, through diminished IκB kinases (IKKs), block production of proinflammatory cytokines (interleukin-6 [IL-6], CCL5, and tumor necrosis factor alpha [TNF-α])...
April 18, 2017: MBio
https://www.readbyqxmd.com/read/28413835/mirna-signatures-can-predict-acute-liver-failure-in-hepatitis-e-infected-pregnant-females
#3
Nirupma Trehanpati, Rashi Sehgal, Sharda Patra, Ashish Vyas, Madavan Vasudevan, Ritu Khosla, Arshi Khanam, Guresh Kumar, Rakhi Maiwall, Gayatri Ramakrishna, Shyam Kottilil, Shiv Kumar Sarin
BACKGROUND: Acute viral hepatitis E (AVH-E) can often result in acute liver failure (ALF) during pregnancy. microRNAs serve as mediators in drug induced liver failure. We investigated their role as a biomarker in predicting ALF due to HEV (ALF-E). METHODS: We performed next generation sequencing and subsequent validation studies in PBMCs of pregnant (P) self limiting AVH-E, ALF due to HEV (ALF-E) and compared with AVH-E in non-pregnant (NP) females and healthy controls...
April 2017: Heliyon
https://www.readbyqxmd.com/read/28401895/integrated-host-and-viral-transcriptome-analyses-reveal-pathology-and-inflammatory-response-mechanisms-to-alv-j-injection-in-spf-chickens
#4
Xi Lan, Yan Wang, Kai Tian, Fei Ye, Huadong Yin, Xiaoling Zhao, Hengyong Xu, Yong Huang, Haibo Liu, John C F Hsieh, Susan J Lamont, Qing Zhu
Avian leukosis virus (ALV) is detrimental to poultry health and causes substantial economic losses from mortality and decreased performance. Because tumorigenesis is a complex mechanism, the regulatory architecture of the immune system is likely to include the added dimensions of modulation by miRNAs and long-noncoding RNA (lncRNA). To characterize the response to ALV challenge, we developed a novel methodology that combines four datasets: mRNA expression and the associated regulatory factors of miRNA and lncRNA, and ALV gene expression...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28389707/the-race-of-10-synthetic-rnai-based-drugs-to-the-pharmaceutical-market
#5
REVIEW
Ricardo Titze-de-Almeida, Catherine David, Simoneide Souza Titze-de-Almeida
Ten years after Fire and Melo's Nobel Prize for discovery of gene silencing by double-stranded RNA, a remarkable progress was achieved in RNA interference (RNAi). Changes in the chemical structure of synthetic oligonucleotides make them more stable and specific, and new delivery strategies became progressively available. The attention of pharmaceutical industry rapidly turned to RNAi, as an opportunity to explore new drug targets. This review addresses nine small-interfering RNAs (siRNAs) and one unique microRNA (miRNA) inhibitor, which entered the phase 2-3 clinical trials...
April 7, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28388330/yellow-fever-virus-modulates-the-expression-of-key-proteins-related-to-the-microrna-pathway-in-the-human-hepatocarcinoma-cell-line-hepg2
#6
Gustavo Moraes Holanda, Samir Mansour Moraes Casseb, Karla Fabiane Lopes Mello, Pedro Fernando Costa Vasconcelos, Ana Cecília Ribeiro Cruz
Yellow fever is a zoonotic disease caused by the yellow fever virus (YFV) and transmitted by mosquitoes of the family Culicidae. It is well known that cellular and viral microRNAs (miRNAs) are involved in modulation of viral and cellular gene expression, as well as immune response, and are considered by the scientific community as possible targets for an effective therapy against viral infections. This regulation may be involved in different levels of infection and clinical symptomatology. We used viral titration techniques, viral kinetics from 24 to 96 hours postinfection (hpi), and analyzed the expression of key proteins related to the miRNA pathway by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)...
April 7, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28382020/h9n2-avian-influenza-virus-protein-pb1-enhances-the-immune-responses-of-bone-marrow-derived-dendritic-cells-by-down-regulating-mir375
#7
Jian Lin, Jing Xia, Chong Z Tu, Ke Y Zhang, Yan Zeng, Qian Yang
Polymerase basic protein 1 (PB1), the catalytic core of the influenza A virus RNA polymerase complex, is essential for viral transcription and replication. Dendritic cells (DCs) possess important antigen presenting ability and a crucial role in recognizing and clearing virus. MicroRNA (miRNA) influence the development of DCs and their ability to present antigens as well as the ability of avian influenza virus (AIV) to infect host cells and replicate. Here, we studied the molecular mechanism underlying the miRNA-mediated regulation of immune function in mouse DCs...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28374846/infections-of-virulent-and-avirulent-viruses-differentially-influenced-the-expression-of-dicer-1-ago-1-and-micrornas-in-bombus-terrestris
#8
Jinzhi Niu, Ivan Meeus, Dieter Im De Coninck, Dieter Deforce, Kayvan Etebari, Sassan Asgari, Guy Smagghe
The microRNA (miRNA) pathway is well established to be involved in host-pathogen interactions. As key insect pollinators, bees are suffering from widely spreading viruses, especially honeybees and bumblebees. In order to better understand bee-virus interaction, we comparatively analyzed the involvement of the bumblebee miRNA pathway upon infection by two different viruses. In our setup, an avirulent infection is induced by slow bee paralysis virus (SBPV) and a virulent infection is induced by Israeli acute paralysis virus (IAPV)...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28368488/plasma-microrna-levels-are-associated-with-hbeag-status-and-treatment-response-in-chronic-hepatitis-b-patients
#9
Meike H van der Ree, Louis Jansen, Zita Kruize, Ad C van Nuenen, Karel A van Dort, R Bart Takkenberg, Hendrik W Reesink, Neeltje A Kootstra
Background: Hepatitis B virus (HBV) modulates miRNA expression to support viral replication. The aim of this study was to identify miRNAs associated with HBeAg-status and response to antiviral therapy in chronic hepatitis B (CHB) patients, and to assess if these miRNAs are secreted by hepatoma cells. Methods: Plasma miRNA levels were measured by RT-qPCR in healthy controls (n=10), and pre-treatment samples of an identification cohort (n=24) and a confirmation cohort (n=64) of CHB patients treated with peg-interferon/nucleotide analogue combination therapy...
March 23, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28368362/sus-scrofa-mir-204-and-mir-4331-negatively-regulate-swine-h1n1-2009-influenza-a-virus-replication-by-targeting-viral-ha-and-ns-respectively
#10
Shishuo Zhang, Ruifang Wang, Huijuan Su, Biaoxiong Wang, Suolang Sizhu, Zhixin Lei, Meilin Jin, Huanchun Chen, Jiyue Cao, Hongbo Zhou
The prevalence of swine pandemic H1N1/2009 influenza A virus (SIV-H1N1/2009) in pigs has the potential to generate novel reassortant viruses, posing a great threat to human health. Cellular microRNAs (miRNAs) have been proven as promising small molecules for regulating influenza A virus replication by directly targeting viral genomic RNA. In this study, we predicted potential Sus scrofa (ssc-, swine) miRNAs targeting the genomic RNA of SIV-H1N1/2009 by RegRNA 2.0, and identified ssc-miR-204 and ssc-miR-4331 to target viral HA and NS respectively through dual-luciferase reporter assays...
April 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28363461/hsv1-latent-transcription-and-non-coding-rna-a-critical-retrospective
#11
REVIEW
Dane Phelan, Enrico R Barrozo, David C Bloom
Virologists have invested great effort into understanding how the herpes simplex viruses and their relatives are maintained dormant over the lifespan of their host while maintaining the poise to remobilize on sporadic occasions. Piece by piece, our field has defined the tissues in play (the sensory ganglia), the transcriptional units (the latency-associated transcripts), and the responsive genomic region (the long repeats of the viral genomes). With time, the observed complexity of these features has compounded, and the totality of viral factors regulating latency are less obvious...
March 6, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28362190/hpv-epigenetic-mechanisms-related-to-oropharyngeal-and-cervix-cancers
#12
Marina Di Domenico, Giancarlo Giovane, Soumaya Kouidhi, Rosamaria Iorio, Maurizio Romano, Francesco De Francesco, Antonia Feola, Camilla Siciliano, Luigi Califano, Antonio Giordano
Human Papilloma Virus infection is very frequent in humans and is mainly transmitted sexually. The majority of infections are transient and asymptomatic, however, if the infection persists, it can occur with a variety of injuries to skin and mucous membranes, depending on the type of HPV involved. Some types of HPV are classified as high oncogenic risk as associated with the onset of cancer. The tumors most commonly associated with HPV are cervical and oropharyngeal cancer, epigenetic mechanisms related to HPV infection include methylation changes to host and viral DNA and chromatin modification in host species...
March 31, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28357807/dual-microrna-to-cellular-prion-protein-inhibits-propagation-of-pathogenic-prion-protein-in-cultured-cells
#13
Sang-Gyun Kang, Chiye Kim, Judd Aiken, Han Sang Yoo, Debbie McKenzie
Prion diseases are fatal transmissible neurodegenerative disorders affecting humans and various mammals. In spite of intensive efforts, there is no effective cure or treatment for prion diseases. Cellular forms of prion protein (PrP(C)) is essential for propagation of abnormal isoforms of prion protein (PrP(Sc)) and pathogenesis. The effect of an artificial dual microRNA (DmiR) on PrP(C) suppression and resultant inhibition of prion replication was determined using prion-infectible cell cultures: differentiated C2C12 culture and primary mixed neuronal and glial cells culture (MNGC)...
March 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28356525/microrna-mir-27-inhibits-adenovirus-infection-by-suppressing-the-expression-of-snap25-and-txn2
#14
M Machitani, F Sakurai, K Wakabayashi, K Nakatani, M Tachibana, H Mizuguchi
Recent studies have reported that host microRNAs (miRNAs) regulate infection with several types of viruses via various mechanisms, and that inhibition of the miRNA processing factors enhances or prevents viral infection. However, it has not been clarified whether these effects of miRNAs extend to adenovirus (Ad) infection. Here we show that miR-27a/b efficiently inhibit infection with an Ad via the down-regulation of SNAP25 and TXN2, which are members of the SNARE proteins and the thioredoxin family, respectively...
March 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28330853/noncoding-mirnas-bridge-virus-infection-and-host-autophagy-in-shrimp-in-vivo
#15
Yaodong He, Yuechao Sun, Xiaobo Zhang
Autophagy is known to be involved in viral infection. However, the relationship between autophagy and viral infection has not been characterized. MicroRNAs (miRNAs), important regulators of gene transcription, play central roles in many biologic processes, including autophagy and viral infection. It was therefore of interest to investigate the miRNAs regulating viral infection and host autophagy. In this study the viral infection (white spot syndrome virus, WSSV) correlated positively with the host autophagy in shrimp...
March 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28325684/monitoring-and-visualizing-microrna-dynamics-during-live-cell-differentiation-using-microrna-responsive-non-viral-reporter-vectors
#16
Hideyuki Nakanishi, Kenji Miki, Kaoru R Komatsu, Masayuki Umeda, Megumi Mochizuki, Azusa Inagaki, Yoshinori Yoshida, Hirohide Saito
MicroRNA (miRNA) activity differs with cell type, suggesting it can be used as a cell marker. In this study, we developed novel miRNA-responsive non-viral reporter vectors to continuously monitor and visualize miRNA dynamics during differentiation and to efficiently purify target living cells. Each vector codes miRNA-responsive and reference reporter genes in a single mRNA. These two genes are independent modules but transcribed by a single promoter, which enables us to distinguish miRNA-mediated post-transcriptional repression from transcriptional repression...
March 2, 2017: Biomaterials
https://www.readbyqxmd.com/read/28323040/-machine-learning-based-identification-of-endogenous-cellular-microrna-sponges-against-viral-micrornas
#17
Soowon Kang, Seunghyun Park, Sungroh Yoon, Hyeyoung Min
A "miRNA sponge" is an artificial oligonucleotide-based miRNA inhibitor containing multiple binding sites for a specific miRNA. Each miRNA sponge can bind and sequester several miRNA copies, thereby decreasing the cellular levels of the target miRNA. In addition to developing artificial miRNA sponges, scientists have sought endogenous RNA transcripts and found that long non-coding RNAs, competing endogenous RNAs, pseudogenes, circular RNAs, and coding RNAs could act as miRNA sponges under precise conditions...
March 17, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28298907/mir-21a-5p-contributes-to-porcine-hemagglutinating-encephalomyelitis-virus-proliferation-via-targeting-cask-interactive-protein1-in-vivo-and-vitro
#18
Xiaoling Lv, Kui Zhao, Yungang Lan, Zi Li, Ning Ding, Jingjing Su, Huijun Lu, Deguang Song, Feng Gao, Wenqi He
Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurovirulent coronavirus that can cause nervous symptoms in piglets with muscle tremors, hind limb paralysis, and nystagmus. Whether some factors affect virus replication and proliferation had not been fully understood in the course of nerve damage caused by PHEV infection. In recent years, some reports suggested that miRNA might play a key regulatory role in viral infection. In this study, we found the miR-21a-5p is notably up-regulated in the brains of mice and N2a cells infected with PHEV, and it down-regulated the expression of CASK-interactive protein1 (Caskin1) by directly targeting the 3'-UTR of Caskin1 using a Dual-Luciferase reporter assay...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28296624/dusp11-an-rna-phosphatase-that-regulates-host-and-viral-non-coding-rnas-in-mammalian-cells
#19
James M Burke, Christopher S Sullivan
Dual-specificity phosphatase 11 (DUSP11) is a conserved protein tyrosine phosphatase (PTP) in metazoans. The cellular substrates and physiological activities of DUSP11 remain largely unknown. In nematodes, DUSP11 is required for normal development and RNA interference against endogenous RNAs (endo-RNAi) via molecular mechanisms that are not well understood. However, mammals lack analogous endo-RNAi pathways and consequently, a role for DUSP11 in mammalian RNA silencing was unanticipated. Recent work from our lab demonstrated that DUSP11 activity alters the silencing potential of noncanonical viral miRNAs in mammalian cells...
March 15, 2017: RNA Biology
https://www.readbyqxmd.com/read/28286035/identification-and-characterization-of-two-putative-micrornas-encoded-by-bombyx-mori-cypovirus
#20
Zhong-Hua Pan, Ping Wu, Kun Gao, Cheng-Xiang Hou, Guang-Xing Qin, Tao Geng, Xi-Jie Guo
Viral microRNAs (miRNAs) have been demonstrated to play important roles in virus-host interactions. Some RNA virus-encoded miRNAs have been reported to promote viral replication and may be used as potential drug targets. Bombyx mori cypovirus (BmCPV), an important pathogen of silkworm, is a double-stranded RNA virus frequently causing serious damages in sericulture. Research on miRNA encoded by BmCPV may be useful to elucidate the BmCPV-host interaction and to develop new anti-viral methods. In our previous study, small RNA libraries of the midgut of BmCPV-infected silkworm have been generated by deep sequencing and several BmCPV-encoded putative miRNAs were predicted...
March 8, 2017: Virus Research
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