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https://www.readbyqxmd.com/read/28820725/understanding-hepatitis-c-virus-drug-resistance-clinical-implications-for-current-and-future-regimens
#1
David L Wyles, Anne F Luetkemeyer
Viral resistance to direct-acting antiviral drugs may impact their effectiveness during treatment of hepatitis C virus (HCV) infection. Most data on HCV drug resistance concern genotypes 1 and 3. The clinical impact of resistance to HCV nonstructural protein 5A (NS5A) inhibitors and a practical approach to indications and methods for resistance testing are discussed.
July 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28815532/hepatitis-c-virus-replication
#2
Tetsuro Suzuki
Viruses use synthetic mechanism and organelles of the host cells to facilitate their replication and make new viruses. Host's ATP provides necessary energy. Hepatitis C virus (HCV) is a major cause of liver disease. Like other positive-strand RNA viruses, the HCV genome is thought to be synthesized by the replication complex, which consists of viral- and host cell-derived factors, in tight association with structurally rearranged vesicle-like cytoplasmic membranes. The virus-induced remodeling of subcellular membranes, which protect the viral RNA from nucleases in the cytoplasm, promotes efficient replication of HCV genome...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28809743/outcomes-for-cirrhotic-patients-with-hepatitis-c-virus-1b-treated-with-asunaprevir-and-daclatasvir-combination
#3
Akihiro Tamori, Hoang Hai, Sawako Uchida-Kobayashi, Masaru Enomoto, Ritsuzo Kozuka, Hiroyuki Motoyama, Etsushi Kawamura, Atsushi Hagihara, Yuga Teranishi, Kanako Yoshida, Hiroyasu Morikawa, Yoshiki Murakami, Norifumi Kawada
BACKGROUND: The efficacy and safety of asunaprevir + daclatasvir combination therapy for treatment of hepatitis C virus (HCV) in compensated cirrhotic patients was not fully evaluated in real-world. Outcomes were assessed in cirrhotic patients with sustained viral response (SVR). MATERIAL AND METHODS: A total of 145 patients without resistance-associated substitutions (RASs) at L31 and Y93 in the nonstructural protein 5A of HCV genotype 1b, consisting of 49 hepatic cirrhotic and 96 non-cirrhotic patients, were enrolled to the therapy...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28807904/no-clinically-relevant-drug-drug-interactions-between-methadone-or-buprenorphine-naloxone-and-anti-viral-combination-glecaprevir-and-pibrentasvir
#4
Matthew Kosloski, Weihan Zhao, Armen Asatryan, Jens Kort, Pierre Geoffroy, Wei Liu
The combination of glecaprevir (formerly ABT-493), a nonstructural (NS) protein 3/4A protease inhibitor, and pibrentasvir (formerly ABT-530), a NS5A protein inhibitor, is being developed as treatment for HCV genotype 1-6 infection. The pharmacokinetics, pharmacodynamics, safety, and tolerability of methadone or buprenorphine/naloxone when coadministered with the glecaprevir and pibrentasvir combination in HCV-negative subjects on stable opioid maintenance therapy were investigated in a Phase 1, single-center, two-arm, multiple-dose, open-label sequential study...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28806616/parvovirus-b19-integration-into-human-cd36-erythroid-progenitor-cells
#5
Tyler Janovitz, Susan Wong, Neal S Young, Thiago Oliveira, Erik Falck-Pedersen
The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome...
August 11, 2017: Virology
https://www.readbyqxmd.com/read/28765561/antibodies-against-modified-ns1-wing-domain-peptide-protect-against-dengue-virus-infection
#6
Yen-Chung Lai, Yung-Chun Chuang, Ching-Chuan Liu, Tzong-Shiann Ho, Yee-Shin Lin, Robert Anderson, Trai-Ming Yeh
Dengue is the most common mosquito-transmitted viral infection for which an improved vaccine is still needed. Although nonstructural protein-1 (NS1) immunization can protect mice against dengue infection, molecular mimicry between NS1 and host proteins makes NS1-based vaccines challenging to develop. Based on the epitope recognized by the anti-NS1 monoclonal Ab (mAb) 33D2 which recognizes a conserved NS1 wing domain (NS1-WD) region but not host proteins, we synthesized a modified NS1-WD peptide to immunize mice...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28759334/b-cell-tetramer-development-for-veterinary-vaccinology
#7
Michael C Rahe, Kevin L Gustafson, Michael P Murtaugh
Immunological memory is elicited after either vaccination or natural exposure to a pathogen and is essential for protection against re-exposure. Despite its critical importance, the ability to interrogate the veterinary animal memory immune response has long been hindered by a paucity of tools to assess immunological memory. As a result, the evaluation and analysis of protective immune responses that predict immune protection in food and fiber animals and facilitate vaccine development are obstructed. To fill this gap in knowledge in swine, we created a B cell tetramer to porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 7 (nsp7) to efficiently and effectively investigate the memory B cell response, a hallmark of anti-viral immunity...
July 31, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28758632/tree-shrew-a-potential-animal-model-for-hepatitis-c-supports-the-infection-and-replication-of-hcv-in-vitro-and-in-vivo
#8
Yue Feng, Yue-Mei Feng, Caixia Lu, Yuanyuan Han, Li Liu, Xiaomei Sun, Jiejie Dai, Xueshan Xia
The tree shrew (Tupaia belangeri chinensis), a small animal widely distributed in Southeast Asia and southwest China, has the potential to be developed as an animal model for hepatitis C. To determine the susceptibility of the tree shrew to hepatitis C virus (HCV) infection in vitro and in vivo, a well-established HCV, produced from the J6/JFH1-Huh7.5.1 culture system, was used to infect cultured primary tupaia hepatocytes (PTHs) and tree shrews. The in vitro results showed that HCV genomic RNA and HCV-specific nonstructural protein 5A (NS5A) could be detected in the PTH cell culture from days 3-15 post-infection, although the viral load was lower than that observed in Huh7...
July 31, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28747493/role-of-viral-hemorrhagic-septicemia-virus-matrix-m-protein-in-suppressing-host-transcription
#9
Qi Ke, Wade Weaver, Adam Pore, Bartolomeo Gorgoglione, Julia Halo Wildschutte, Peng Xiao, Brian S Shepherd, Allyn Spear, Krishnamurthy Malathi, Carol A Stepien, Vikram N Vakharia, Douglas W Leaman
Viral Hemorrhagic Septicemia virus (VHSV) is a pathogenic fish rhabdovirus found in discrete locales throughout the northern hemisphere. VHSV infection of fish cells leads to upregulation of the host's virus detection response, but the virus quickly suppresses interferon (IFN) production and antiviral genes expression. By systematically screening each of the six VHSV structural and nonstructural genes, we have identified matrix protein (M) as its most potent anti-host protein. VHSV-IVb M alone suppressed mitochondrial antiviral signaling protein (MAVS) and type I IFN-induced gene expression in a dose-dependent manner...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28746382/gelatin-nanoparticles-enhance-delivery-of-hepatitis-c-virus-recombinant-ns2-gene
#10
Salwa Sabet, Marina A George, Haidan M El-Shorbagy, Heba Bassiony, Khaled Y Farroh, Tareq Youssef, Taher A Salaheldin
BACKGROUND: Development of an effective non-viral vaccine against hepatitis C virus infection is of a great importance. Gelatin nanoparticles (Gel.NPs) have an attention and promising approach as a viable carrier for delivery of vaccine, gene, drug and other biomolecules in the body. AIM OF WORK: The present study aimed to develop stable Gel.NPs conjugated with nonstructural protein 2 (NS2) gene of Hepatitis C Virus genotype 4a (HCV4a) as a safe and an efficient vaccine delivery system...
2017: PloS One
https://www.readbyqxmd.com/read/28735962/enhancement-of-antiviral-capacity-of-transgenic-silkworms-against-cytoplasmic-polyhedrosis-virus-via-knockdown-of-multiple-viral-genes
#11
Liang Jiang, Zhengwen Peng, Huizhen Guo, Jingchen Sun, Qiang Sun, Fei Xia, Chunlin Huang, Guowen Xu, Qingyou Xia
Bombyx mori cytoplasmic polyhedrosis virus (BmCPV), a major pathogen of silkworms, causes serious economic losses in sericulture. The BmCPV genome contains 10 discrete dsRNA segments; among these, S1, S2, S3, S4, S6, and S7 encode virus structural proteins, whereas S5, S8, S9, and S10 encode nonstructural proteins. In an attempt to create an anti-BmCPV silkworm strain, we constructed transgenic RNAi vector pb-CNS for knockdown of S5, S8, S9, and S10, and pb-SNS targeting S1, S2, S4, S5, and S8. Transgenic silkworm line CNS and SNS were generated via microinjection of the practical diapause silkworm strain Furong...
July 20, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28720733/dengue-virus-hijacks-a-noncanonical-oxidoreductase-function-of-a-cellular-oligosaccharyltransferase-complex
#12
David L Lin, Natalia A Cherepanova, Leonia Bozzacco, Margaret R MacDonald, Reid Gilmore, Andrew W Tai
Dengue virus (DENV) is the most common arboviral infection globally, infecting an estimated 390 million people each year. We employed a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen to identify host dependency factors required for DENV propagation and identified the oligosaccharyltransferase (OST) complex as an essential host factor for DENV infection. Mammalian cells express two OSTs containing either STT3A or STT3B. We found that the canonical catalytic function of the OSTs as oligosaccharyltransferases is not necessary for DENV infection, as cells expressing catalytically inactive STT3A or STT3B are able to support DENV propagation...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28715653/inhibition-of-nf-%C3%AE%C2%BAb-activity-by-the-porcine-epidemic-diarrhea-virus-nonstructural-protein-1-for-innate-immune-evasion
#13
Qingzhan Zhang, Jinyou Ma, Dongwan Yoo
Porcine epidemic diarrhea virus emerged in the US is known to suppress the type I interferons response during infection. In the present study using porcine epithelial cells, we showed that PEDV inhibited both NF-κB and proinflammatory cytokines. PEDV blocked the p65 activation in infected cells and suppressed the PRD II-mediated NF-κB activity. Of the total of 22 viral proteins, nine proteins were identified as NF-κB antagonists, and nsp1 was the most potent suppressor of proinflammatory cytokines. Nsp1 interfered the phosphorylation and degradation of IκBα, and thus blocked the p65 activation...
July 14, 2017: Virology
https://www.readbyqxmd.com/read/28701392/partially-uncleaved-alphavirus-replicase-forms-spherule-structures-in-the-presence-and-absence-of-rna-template
#14
Kirsi Hellström, Katri Kallio, Age Utt, Tania Quirin, Eija Jokitalo, Andres Merits, Tero Ahola
Alphaviruses are positive-strand RNA viruses expressing their replicase as a polyprotein P1234, which is cleaved to four final products, nonstructural proteins nsP1-nsP4. The replicase proteins together with viral RNA and host factors form membrane invaginations termed spherules, which act as the replication complexes producing progeny RNAs. We have previously shown that the wild type alphavirus replicase requires a functional RNA template and active polymerase to generate spherule structures. However, we now find that specific partially processed forms of the replicase proteins alone can give rise to membrane invaginations, in the absence of RNA or replication...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28698274/noroviruses-co-opt-the-function-of-host-proteins-vapa-and-vapb-for-replication-via-a-phenylalanine-phenylalanine-acidic-tract-motif-mimic-in-nonstructural-viral-protein-ns1-2
#15
Broc T McCune, Wei Tang, Jia Lu, James B Eaglesham, Lucy Thorne, Anne E Mayer, Emily Condiff, Timothy J Nice, Ian Goodfellow, Andrzej M Krezel, Herbert W Virgin
The Norovirus genus contains important human pathogens, but the role of host pathways in norovirus replication is largely unknown. Murine noroviruses provide the opportunity to study norovirus replication in cell culture and in small animals. The human norovirus nonstructural protein NS1/2 interacts with the host protein VAMP-associated protein A (VAPA), but the significance of the NS1/2-VAPA interaction is unexplored. Here we report decreased murine norovirus replication in VAPA- and VAPB-deficient cells. We characterized the role of VAPA in detail...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28693575/interleukin-2-enhancer-binding-factor-2-interacts-with-the-nsp9-or-nsp2-of-porcine-reproductive-and-respiratory-syndrome-virus-and-exerts-negatively-regulatory-effect-on-the-viral-replication
#16
Xuexia Wen, Ting Bian, Zhibang Zhang, Lei Zhou, Xinna Ge, Jun Han, Xin Guo, Hanchun Yang, Kangzhen Yu
BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes reproductive failures in sows and respiratory diseases in growing pigs, resulting in huge economic loss for the pig production worldwide. The nonstructural protein 9 (nsp9) and nonstructural protein 2 (nsp2) of PRRSV are known to play important roles in viral replication. Cellular interleukin-2 enhancer binding factor 2 (ILF2) participates in many cellular pathways and involves in life cycle of some viruses...
July 11, 2017: Virology Journal
https://www.readbyqxmd.com/read/28690868/mirna-200c-3p-is-crucial-in-acute-respiratory-distress-syndrome
#17
Qiang Liu, Jianchao Du, Xuezhong Yu, Jun Xu, Fengming Huang, Xiaoyun Li, Cong Zhang, Xiao Li, Jiahui Chang, Daozhen Shang, Yan Zhao, Mingyao Tian, Huijun Lu, Jiantao Xu, Chang Li, Huadong Zhu, Ningyi Jin, Chengyu Jiang
Influenza infection and pneumonia are known to cause much of their mortality by inducing acute respiratory distress syndrome (ARDS), which is the most severe form of acute lung injury (ALI). Angiotensin-converting enzyme 2 (ACE2), which is a negative regulator of angiotensin II in the renin-angiotensin system, has been reported to have a crucial role in ALI. Downregulation of ACE2 is always associated with the ALI or ARDS induced by avian influenza virus, severe acute respiratory syndrome-coronavirus, respiratory syncytial virus and sepsis...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28690069/bovine-leukemia-virus-g4-enhances-virus-production
#18
Hironobu Murakami, Shotaro Asano, Jumpei Uchiyama, Reiichiro Sato, Masahiro Sakaguchi, Kenji Tsukamoto
The nonstructural G4 gene of bovine leukemia virus (BLV) has been thought to function in virus replication. However, the discovery of the AS1 gene on the antisense strand of the G4 gene has affected this interpretation. In this study, we investigated the function of G4 in virus production independent of the AS1 gene using a reverse genetic approach, and briefly examined the association of the G4 protein with Tax, which is also a nonstructural protein that promotes virus replication. First, we constructed a mutant molecular clone of BLV with a nonsense mutation in G4 that had a minimal effect on the AS1 gene...
July 6, 2017: Virus Research
https://www.readbyqxmd.com/read/28680969/differential-antagonism-of-human-innate-immune-responses-by-tick-borne-phlebovirus-nonstructural-proteins
#19
Veronica V Rezelj, Ping Li, Vidyanath Chaudhary, Richard M Elliott, Dong-Yan Jin, Benjamin Brennan
In recent years, several newly discovered tick-borne viruses causing a wide spectrum of diseases in humans have been ascribed to the Phlebovirus genus of the Bunyaviridae family. The nonstructural protein (NSs) of bunyaviruses is the main virulence factor and interferon (IFN) antagonist. We studied the molecular mechanisms of IFN antagonism employed by the NSs proteins of human apathogenic Uukuniemi virus (UUKV) and those of Heartland virus (HRTV) and severe fever with thrombocytopenia syndrome virus (SFTSV), both of which cause severe disease...
May 2017: MSphere
https://www.readbyqxmd.com/read/28665723/kidney-cell-adapted-infectious-bronchitis-arkdpi-vaccine-is-stable-and-protective
#20
R A Zegpi, C Breedlove, V L van Santen, C R Rasmussen-Ivey, H Toro
We previously demonstrated that adaptation of an embryo-attenuated infectious bronchitis virus (IBV) Arkansas (Ark) Delmarva Poultry Industry (DPI)-derived vaccine to chicken embryo kidney (CEK) cells (CEKp7) shifted the virus population towards homogeneity in spike (S) and nonstructural protein genes. Moreover, the typical Ark vaccine subpopulations emerging in chickens vaccinated with commercial Ark vaccines were not detected in chickens vaccinated with CEKp7, indicating that kidney-cell adaptation drastically increased the stability of the vaccine virus population in chickens...
June 2017: Avian Diseases
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