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https://www.readbyqxmd.com/read/28453983/discovery-and-mechanism-of-action-of-novel-baicalein-modified-derivatives-as-potent-antihepatitis-agent
#1
Ji Ma, Tengfei Li, Xinwei Han, Huifeng Yuan, Haijun Liang, Yanping Wang, Xinwei Wang, Yuxiu Duan, Aihui Li, Huilian Song, Daokun Yang
Anti-hepatitis B virus (HBV) activity was evaluated in HepG2 2.2.15 cells by novel Baicalein derivatives. The result showed that compounds 4k and 4h was found to be effective anti-HBV agent. Further, the effect of compounds 4k and 4h showed dose-dependent inhibition of HBV-DNA as compared to control together with significant inhibition of HbeAG and HbsAG expression in the tested dose. Both compounds showed considerable affinity against the HepG2.2.15 cells. Moreover, the docking study of compound 4k was carried out with HLA molecule showing excellent intermolecular interactions with the receptor via creation of numerous bonds with Ser5, Thr27, Asp29 and Phe8...
April 25, 2017: Virology
https://www.readbyqxmd.com/read/28448850/perturbation-of-drosha-and-dicer-expression-by-human-papillomavirus-16-oncoproteins
#2
Mallory E Harden, Karl Munger
Many tumors, including cervical carcinoma, show dysregulated expression of the microRNA processing machinery, specifically DROSHA and DICER. Some cervical cancers exhibit chromosome 5p amplifications and DROSHA is the most significantly upregulated transcript and is observed in all tumors with 5p gain. DROSHA and DICER mRNA levels, however, are higher in HPV positive cancer lines than in an HPV negative cervical carcinoma line. We show that high-risk HPV E6/E7 expression in HPV negative C33A cervical carcinoma cells and primary human epithelial cell causes increased expression of DROSHA and DICER mRNA and protein...
April 24, 2017: Virology
https://www.readbyqxmd.com/read/28448849/regulation-of-the-human-papillomavirus-type-16-late-promoter-by-transcriptional-elongation
#3
William K Songock, Matthew L Scott, Jason M Bodily
Transcripts from the late promoter of human papillomavirus type 16 (HPV16) are upregulated upon host cell differentiation. Differentiation-dependent transcript regulation is thought to sequester viral antigens in the uppermost epithelial layers, facilitating immune evasion. The mechanisms regulating late promoter upregulation during differentiation are poorly characterized. We show that the late promoter is upregulated at the transcriptional level and that the viral enhancer stimulates promoter activity. Using kinase inhibition and chromatin immunoprecipitation analysis, we show evidence for differentiation-dependent enhancement of transcript elongation...
April 24, 2017: Virology
https://www.readbyqxmd.com/read/28448848/transmissible-gastroenteritis-virus-infection-induces-nf-%C3%AE%C2%BAb-activation-through-rlr-mediated-signaling
#4
Zhen Ding, Kang An, Lilan Xie, Wei Wu, Ruoxi Zhang, Dang Wang, Ying Fang, Huanchun Chen, Shaobo Xiao, Liurong Fang
Transmissible gastroenteritis virus (TGEV) is a porcine enteric coronavirus which causes lethal severe watery diarrhea in piglets. The pathogenesis of TGEV is strongly associated with inflammation. In this study, we found that TGEV infection activates transcription factors NF-κB, IRF3 and AP-1 in a time- and dose-dependent manner in porcine kidney cells. Treatment with the NF-κB-specific inhibitor BAY11-7082 significantly decreased TGEV-induced proinflammatory cytokine production, but did not affect virus replication...
April 24, 2017: Virology
https://www.readbyqxmd.com/read/28441586/kobuvirus-vp3-protein-restricts-the-ifn-%C3%AE-triggered-signaling-pathway-by-inhibiting-stat2-irf9-and-stat2-stat2-complex-formation
#5
Qianqian Peng, Xi Lan, Chen Wang, Yujie Ren, Ningning Yue, Junyong Wang, Bo Zhong, Qiyun Zhu
Emerged porcine kobuvirus (PKV) has adversely affected the global swine industry since 2008, but the etiological biology of PKV is unclear. Screening PKV-encoded structural and non-structural proteins with a type I IFN-responsive luciferase reporter showed that PKV VP3 protein inhibited the IFN-β-triggered signaling pathway, resulting in the decrease of VSV-GFP replication. QPCR data showed that IFN-β downstream cytokine genes were suppressed without cell-type specificity as well. The results from biochemical experiments indicated that PKV VP3 associated with STAT2 and IRF9, and interfered with the formation of the STAT2-IRF9 and STAT2-STAT2 complex, impairing nuclear translocation of STAT2 and IRF9...
April 22, 2017: Virology
https://www.readbyqxmd.com/read/28437636/chimeric-flock-house-virus-protein-a-with-endoplasmic-reticulum-targeting-domain-enhances-viral-replication-and-virus-like-particle-trans-encapsidation-in-plants
#6
Yiyang Zhou, Christopher M Kearney
Flock House virus (FHV) RNA can be trans-encapsidated, entirely in planta, by tobacco mosaic virus coat protein to form virus-like particles (VLPs). Vaccination with these VLPs leads to strong antigen expression in mice and immune-activation. We hypothesize that creating an additional cellular site for replication and/or trans-encapsidation might significantly improve the final output of trans-encapsidated product. FHV protein A was engineered to target the endoplasmic reticulum (ER) via a heterologous tobacco etch virus ER-targeting domain, and was expressed in cis or in trans relative to the replicating FHV RNA1...
April 21, 2017: Virology
https://www.readbyqxmd.com/read/28437635/three-cysteine-residues-of-slc52a1-a-receptor-for-the-porcine-endogenous-retrovirus-a-perv-a-play-a-critical-role-in-cell-surface-expression-and-infectivity
#7
Winston Colon-Moran, Takele Argaw, Carolyn A Wilson
Porcine endogenous retrovirus-A (PERV-A), a gammaretrovirus, infects human cells in vitro, thus raising the potential risk of cross-species transmission in xenotransplantation. Two members of the solute carrier family 52 (SLC52A1 and SLC52A2) are PERV-A receptors. Site-directed mutagenesis of the cDNA encoding SLC52A1 identified that only one of two putative glycosylation signals is occupied by glycans. In addition, we showed that glycosylation of SLC52A1 is not necessary for PERV-A receptor function. We also identified that at a minimum, three cysteine residues are sufficient for SLC52A1 cell surface expression...
April 20, 2017: Virology
https://www.readbyqxmd.com/read/28432928/a-humanized-mouse-based-hiv-1-viral-outgrowth-assay-with-higher-sensitivity-than-in-vitro-qvoa-in-detecting-latently-infected-cells-from-individuals-on-art-with-undetectable-viral-loads
#8
Paige Charlins, Kimberly Schmitt, Leila Remling-Mulder, Louise E Hogan, Emily Hanhauser, Kristen S Hobbs, Frederick Hecht, Steven G Deeks, Timothy J Henrich, Ramesh Akkina
Assays that can verify full viral eradication are essential in the context of achieving a cure for HIV/AIDS. In vitro quantitative viral out growth assays (qVOA) are currently the gold standard for measuring latent HIV-1 but these assays often fail to detect very low levels of replication-competent virus. Here we investigated an alternative in vivo approach for sensitive viral detection using humanized mice (hmVOA). Peripheral blood CD4+ T cell samples from HIV subjects on stable ART with undetectable viral loads by RT-PCR were first assayed by in vitro qVOA...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28432927/type-2-bvdv-n-pro-suppresses-ifn-1-pathway-signaling-in-bovine-cells-and-augments-brsv-replication
#9
Abdulrahman A Alkheraif, Christina L Topliff, Jay Reddy, Chandirasegaran Massilamany, Ruben O Donis, Gregor Meyers, Kent M Eskridge, Clayton L Kelling
Bovine viral diarrhea virus (BVDV) infection induces immunosuppression and in conjunction with bovine respiratory syncytial virus (BRSV) contributes to the bovine respiratory disease complex. Bovine turbinate cells were single or co-infected with type 2 BVDV wild-type (BVDV2-wt), its dysfunctional N(pro) mutant (BVDV2-E), and/or BRSV. BVDV2-E significantly up-regulated PKR, IRF-7, TBK-1, IRF-3, and IFN-β mRNAs based on real-time Q-RT-PCR. BRSV-infected cells expressed significantly up-regulated PKR, IRF-3, IRF-7, and IFN-β mRNAs, whereas BVDV2-wt, but not BVDV2-E, abolished this up-regulation in co-infection...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28432926/tick-borne-encephalitis-virus-infects-human-brain-microvascular-endothelial-cells-without-compromising-blood-brain-barrier-integrity
#10
Martin Palus, Marie Vancova, Jana Sirmarova, Jana Elsterova, Jan Perner, Daniel Ruzek
Alteration of the blood-brain barrier (BBB) is a hallmark of tick-borne encephalitis (TBE), a life-threating human viral neuroinfection. However, the mechanism of BBB breakdown during TBE, as well as TBE virus (TBEV) entry into the brain is unclear. Here, primary human microvascular endothelial cells (HBMECs) were infected with TBEV to study interactions with the BBB. Although the number of infected cells was relatively low in culture (<5%), the infection was persistent with high TBEV yields (>10(6)pfu/ml)...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28432925/structure-of-the-s1-subunit-c-terminal-domain-from-bat-derived-coronavirus-hku5-spike-protein
#11
Xue Han, Jianxun Qi, Hao Song, Qihui Wang, Yanfang Zhang, Ying Wu, Guangwen Lu, Kwok-Yung Yuen, Yi Shi, George F Gao
Accumulating evidence indicates that MERS-CoV originated from bat coronaviruses (BatCoVs). Previously, we demonstrated that both MERS-CoV and BatCoV HKU4 use CD26 as a receptor, but how the BatCoVs evolved to bind CD26 is an intriguing question. Here, we solved the crystal structure of the S1 subunit C-terminal domain of HKU5 (HKU5-CTD), another BatCoV that is phylogenetically related to MERS-CoV but cannot bind to CD26. We observed that the conserved core subdomain and those of other betacoronaviruses (betaCoVs) have a similar topology of the external subdomain, indicating the same ancestor of lineage C betaCoVs...
April 19, 2017: Virology
https://www.readbyqxmd.com/read/28431284/mitovirus-uga-trp-codon-usage-parallels-that-of-host-mitochondria
#12
Max L Nibert
Mitoviruses replicate in mitochondria of their host fungi. They have small RNA genomes that encompass a single ORF encoding the viral RdRp. Since UGA codons encode Trp in fungal mitochondria, the RdRp ORF of a typical mitovirus includes multiple UGA codons. In some mitoviruses, however, the ORF has no such codons, suggesting that these particular viruses may be under selective pressure to exclude them. In this report, new evidence is presented that host fungi whose mitoviruses have no or few UGA codons are distinctive in also having no or few UGA codons in their core mitochondrial genes...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28431283/zika-virus-infection-of-adult-and-fetal-stat2-knock-out-hamsters
#13
Venkatraman Siddharthan, Arnaud J Van Wettere, Rong Li, Jinxin Miao, Zhongde Wang, John D Morrey, Justin G Julander
Zika virus (ZIKV) infection was investigated in adult and fetal STAT2 knock-out (KO) hamsters. Subcutaneous injection of ZIKV of adults resulted in morbidity, mortality, and infection of the uterus, placenta, brain, spinal cord, and testicles, thus providing an opportunity to evaluate congenital ZIKV infection in a second rodent species besides mice. ZIKV-infected cells with morphologies of Sertoli cells and spermatogonia were observed in the testes, which may have implications for sexual transmission and male sterility...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28431282/the-role-of-pharmacologic-modulation-of-autophagy-on-anal-cancer-development-in-an-hpv-mouse-model-of-carcinogenesis
#14
Brooks L Rademacher, Kristina A Matkowskyj, Louise M Meske, Alexis Romero, Hana Sleiman, Evie H Carchman
Autophagy is an intracellular, catabolic process that maintains cellular health. We examined the response of pharmacologic modulation of autophagy in an HPV mouse model of anal carcinogenesis. K14E6/E7 mice were treated with the topical carcinogen DMBA weekly and assessed for tumors over 20 weeks. Concurrently, they were given either chloroquine or BEZ235, to inhibit or induce autophagy, respectively. Time to tumor onset was examined. Immunofluorescence (IF) was performed for LC3β and p62 to examine autophagy...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28431281/dengue-virus-replicates-and-accumulates-in-aedes-aegypti-salivary-glands
#15
Vincent Raquin, Louis Lambrechts
Dengue virus (DENV) is an RNA virus transmitted among humans by mosquito vectors, mainly Aedes aegypti. DENV transmission requires viral dissemination from the mosquito midgut to the salivary glands. During this process the virus undergoes several population bottlenecks, which are stochastic reductions in population size that restrict intra-host viral genetic diversity and limit the efficiency of natural selection. Despite the implications for virus transmission and evolution, DENV replication in salivary glands has not been directly demonstrated...
April 18, 2017: Virology
https://www.readbyqxmd.com/read/28410483/contributions-of-cd8-t-cells-to-the-pathogenesis-of-mouse-adenovirus-type-1-respiratory-infection
#16
Caitlyn T Molloy, Jennifer S Andonian, Harrison M Seltzer, Megan C Procario, Michael E Watson, Jason B Weinberg
CD8 T cells are key components of the immune response to viruses, but their roles in the pathogenesis of adenovirus respiratory infection have not been characterized. We used mouse adenovirus type 1 (MAV-1) to define CD8 T cell contributions to the pathogenesis of adenovirus respiratory infection. CD8 T cell deficiency in β2m(-/-) mice had no effect on peak viral replication in lungs, but clearance of virus was delayed in β2m(-/-) mice. Virus-induced weight loss and increases in bronchoalveolar lavage fluid total protein, IFN-γ, TNF-α, IL-10, CCL2, and CCL5 concentrations were less in β2m(-/-) mice than in controls...
April 11, 2017: Virology
https://www.readbyqxmd.com/read/28399437/genotypic-and-epitope-characteristics-of-group-a-porcine-rotavirus-strains-circulating-in-canada
#17
Omer Naseer, Matthew C Jarvis, Max Ciarlet, Douglas G Marthaler
Surveillance of Rotavirus A (RVA) infections in North America swine populations are limited and not performed over a significant time period to properly assess the diversity of RVA strains in swine. The VP7 (G) and VP4 (P) genes of 32 Canadian RVA strains, circulating between 2009 and 2015 were sequenced, identifying the G3P[13], G5P[7], G9P[7], G9[13], and G9[19] genotype combinations. The Canadian RVA strains were compared to the RVA strains present in the swine ProSystems RCE rotavirus vaccine. The comparison revealed multiple amino acid differences in the G and P antigenic epitopes, regardless of the G and P genotypes but specifically in the Canadian G3, P[13] and P[19] genotypes...
April 8, 2017: Virology
https://www.readbyqxmd.com/read/28399436/phylogenetic-study-of-recombinant-strains-of-potato-virus-y
#18
Kelsie J Green, Celeste J Brown, Stewart M Gray, Alexander V Karasev
Potato virus Y (PVY) exists as a complex of strains, including a growing number of recombinants. Evolution of PVY proceeds through accumulation of mutations and more rapidly through recombination. Here, the role of recombination in PVY evolution and the origin of common PVY recombinants were studied through whole genome analysis of 119 newly sequenced PVY isolates largely from U.S. potato, and subsequent combined phylogenetic and recombination analyses with an additional 166 whole PVY genomes from the GenBank database...
April 8, 2017: Virology
https://www.readbyqxmd.com/read/28399435/inhibition-of-crm1-mediated-nuclear-export-of-influenza-a-nucleoprotein-and-nuclear-export-protein-as-a-novel-target-for-antiviral-drug-development
#19
Nopporn Chutiwitoonchai, Takafumi Mano, Michinori Kakisaka, Hirotaka Sato, Yasumitsu Kondoh, Hiroyuki Osada, Osamu Kotani, Masaru Yokoyama, Hironori Sato, Yoko Aida
An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP...
April 8, 2017: Virology
https://www.readbyqxmd.com/read/28395182/sensitive-luminescent-reporter-viruses-reveal-appreciable-release-of-hepatitis-c-virus-ns5a-protein-into-the-extracellular-environment
#20
Nicholas S Eyre, Amanda L Aloia, Michael A Joyce, Monrat Chulanetra, D Lorne Tyrrell, Michael R Beard
The HCV NS5A protein is essential for viral RNA replication and virus particle assembly. To study the viral replication cycle and NS5A biology we generated an infectious HCV construct with a NanoLuciferase (NLuc) insertion within NS5A. Surprisingly, beyond its utility as a sensitive reporter of cytoplasmic viral RNA replication, we also observed strong luminescence in cell culture fluids. Further analysis using assembly-defective viruses and subgenomic replicons revealed that infectious virus production was not required for extracellular NS5A-NLuc activity but was associated with enrichment of extracellular NS5A-NLuc in intermediate-density fractions similar to those of exosomes and virus particles...
April 7, 2017: Virology
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