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https://www.readbyqxmd.com/read/28446681/minute-virus-of-mice-mvm-inhibits-transcription-of-the-cyclin-b1-gene-during-infection
#1
Matthew S Fuller, Kinjal Majumder, David J Pintel
Replication of minute virus of mice (MVM) induces a sustained cellular DNA damage response (DDR) which the virus then exploits to prepare the nuclear environment for effective parvovirus takeover. An essential aspect of the MVM-induced DDR is the establishment of a potent pre-mitotic block, which we previously found to be independent of activated p21 and ATR/Chk1 signaling. This arrest, unlike others previously reported, depends upon the significant, specific depletion of cyclin B1 and its encoding RNA, which precludes cyclin B1/CDK1 complex function thus preventing mitotic entry...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28444295/features-of-dengue-and-chikungunya-infections-of-colombian-children-under-24%C3%A2-months-of-age-admitted-to-the-emergency-department
#2
Angel Paternina-Caicedo, Fernando De la Hoz-Restrepo, Fredi Díaz-Quijano, William Caicedo-Torres, María Auxiliadora Badillo-Viloria, Doris Bula-Anichiarico, Nelson Alvis-Guzmán, Salim Mattar, Dagna Constenla, Hernando Pinzón-Redondo
We aimed to assess clinical and laboratory differences between dengue and chikungunya in children <24 months of age in a comparative study. We collected retrospective clinical and laboratory data confirmed by NS1/IgM for dengue for 19 months (1 January 2013 to 17 August 2014). Prospective data for chikungunya confirmed by real-time polymerase chain reaction were collected for 4 months (22 September 2014-14 December 2014). Sensitivity and specificity [with 95% confidence interval (CI)] were reported for each disease diagnosis...
April 21, 2017: Journal of Tropical Pediatrics
https://www.readbyqxmd.com/read/28441781/dengue-virus-non-structural-protein-5
#3
REVIEW
Abbas El Sahili, Julien Lescar
The World Health Organization estimates that the yearly number of dengue cases averages 390 million. This mosquito-borne virus disease is endemic in over 100 countries and will probably continue spreading, given the observed trend in global warming. So far, there is no antiviral drug available against dengue, but a vaccine has been recently marketed. Dengue virus also serves as a prototype for the study of other pathogenic flaviviruses that are emerging, like West Nile virus and Zika virus. Upon viral entry into the host cell and fusion of the viral lipid membrane with the endosomal membrane, the viral RNA is released and expressed as a polyprotein, that is then matured into three structural and seven non-structural (NS) proteins...
April 24, 2017: Viruses
https://www.readbyqxmd.com/read/28437586/pathogenesis-of-vascular-leak-in-dengue-virus-infection
#4
REVIEW
Gathsaurie Neelika Malavige, Graham S Ogg
Endothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident during 3-6 days since the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24 to 48 hours and usually shows rapid and complete reversal, suggesting it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as TNFα, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors...
April 24, 2017: Immunology
https://www.readbyqxmd.com/read/28433538/the-ns1-protein-from-influenza-virus-stimulates-translation-initiation-by-enhancing-ribosome-recruitment-to-mrnas
#5
Baptiste Panthu, Olivier Terrier, Coralie Carron, Aurélien Traversier, Antoine Corbin, Laurent Balvay, Bruno Lina, Manuel Rosa-Calatrava, Théophile Ohlmann
The non-structural protein NS1 of influenza A viruses exerts pleiotropic functions during infection. Amongst these functions, NS1 was shown to be involved both in the control of viral and cellular translation; however the mechanism by which this occurs remains to be determined. Thus, we have revisited the role of NS1 in translation by using a combination of influenza infection, mRNA reporter transfection, in vitro functional and biochemical assays. Our data show that the NS1 protein is able to enhance translation of virtually all tested mRNAs with the exception of constructs bearing the Dicistroviruses IRESes (DCV and CrPV), suggesting a role at the level of translation initiation...
April 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28426973/non-linear-enhancement-of-mrna-delivery-efficiencies-by-influenza-a-derived-ns1-protein-engendering-host-gene-inhibition-property
#6
Kyle K L Phua, Yi Liu, Shun Hui Sim
Nucleic acid induced immunogenicity remains a significant impediment in biomedical therapeutics because the innate immune system is a complex network overlaid with functional redundancies. Herein we report that non-structural protein 1 (NS1), an immune evasion protein derived from influenza A virus, when co-delivered in mRNA format is a potent mRNA transfection enhancer without toxicity. Transfection enhancement is mediated by NS1's effector domain through inhibition of IRF3 and PKR, activators of early anti-viral responses as well as CPSF30, a non immunostimulating protein...
April 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28420823/listeria-monocytogenes-serotype-4b-strains-replicate-in-monocytes-macrophages-more-than-the-other-serotypes
#7
Rie Hasebe, Ryo Nakao, Aiko Ohnuma, Takeshi Yamasaki, Hirofumi Sawa, Shinji Takai, Motohiro Horiuchi
We analyzed the pathogenicity of various serotypes of Listeria monocytogenes using a Balb/c mouse intravenous injection model. The survival rates of mice inoculated with strains NS1/2b (serotype 1/2b), NS3b (serotype 3b) and NS 4b (serotype 4b) were 60%, 63.6% and 63.6%, respectively. Although the survival rates were similar, the bacterial growth in the liver of NS3b-infected mice was 144.5-fold higher than that in the liver of NS4b-infected mice. Histopathological analyses suggest that the NS4b strain replicated more in monocytes/macrophages, whereas the NS3b strain replicated more in hepatocytes...
April 17, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28411164/high-levels-of-local-inter-and-intra-host-genetic-variation-of-west-nile-virus-and-evidence-of-fine-scale-evolutionary-pressures
#8
Dylan J Ehrbar, Kiet A Ngo, Scott R Campbell, Laura D Kramer, Alexander T Ciota
West Nile virus (WNV; Flaviviridae, Flavivirus) has been endemic in New York State (NYS) since its 1999 introduction, yet prevalence in Culex mosquitoes varies substantially over small spatial and temporal scales. It is unclear if viral genetics plays a role in this variability, as genetic and phenotypic characterization on local scales has generally been lacking. In addition, intrahost diversity of circulating strains have not been fully characterized despite the documented role of minority variants in viral fitness and virulence...
April 12, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28400751/ethanolic-extract-of-melia-fructus-has-anti-influenza-a-virus-activity-by-affecting-viral-entry-and-viral-rna-polymerase
#9
Young-Hee Jin, Jang-Gi Choi, Won-Kyung Cho, Jin Yeul Ma
Meliae Fructus (MF) is the dried ripe fruit of Melia toosendan Siebold et Zuccarini, Meliaceae family. MF is widely used in traditional medicine to treat inflammation and helminthic infection and has anti-bacterial, anti-oxidant, anti-cancer, anti-inflammatory, and analgesic activities. However, potential anti-influenza properties of MF have yet to be investigated. We determined whether an ethanolic extract of MF (EMF) has anti-viral activity via an EMF pre-, co-, and post-treatment assay, using the Influenza A/PR/8/34 and H3N2 virus on Madin-Darby canine kidney (MDCK) cells...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28400226/in-vitro-effect-of-human-cathelicidin-antimicrobial-peptide-ll-37-on-dengue-virus-type-2
#10
K Alagarasu, P S Patil, P Shil, M Seervi, M B Kakade, H Tillu, A Salunke
Human Cathelicidin antimicrobial peptide LL-37 is known to have antiviral activity against many viruses. In the present study, we investigated the in-vitro effect of LL-37 on dengue virus type 2 (DENV-2) infection and replication in Vero E6 cells. To study the effect of pretreatment of virus or cells with LL-37, the virus was pretreated with different concentrations of LL-37 (2.5μM-15μM) or scrambled (Scr) LL-37(5μM-15μM) and used for infection or the cells were first treated with LL-37 and infected. To study the effect of LL-37 post infection (PI), the cells were infected first followed by addition of LL-37 to the culture medium 24h after infection...
April 9, 2017: Peptides
https://www.readbyqxmd.com/read/28395999/the-ns1-protein-of-h5n6-feline-influenza-virus-inhibits-feline-beta-interferon-response-by-preventing-nf-%C3%AE%C2%BAb-and-irf3-activation
#11
Lifang Wang, Xinliang Fu, Yun Zheng, Pei Zhou, Bo Fang, San Huang, Xin Zhang, Jidang Chen, Zongxi Cao, Jin Tian, Shoujun Li
Despite the apparent lack of a feline influenza virus lineage, cats are susceptible to infection by influenza A viruses. Here, we characterized in vitro A/feline/Guangdong/1/2015, an H5N6 avian influenza virus recently isolated from cats. A/feline/Guangdong/1/2015 replicated to high titers and caused CPE in feline kidney cells. We determined that infection with A/feline/Guangdong/1/2015 did not activate the IFN-β promoter, but inhibited it by blocking the activation of NF-κB and IRF3. We also determined that the viral NS1 protein mediated the block, and that the dsRNA binding domain of NS1 was essential to perform this function...
April 7, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28394300/computational-identification-of-antibody-epitopes-on-the-dengue-virus-ns1-protein
#12
Martina L Jones, Fiona S Legge, Kebaneilwe Lebani, Stephen M Mahler, Paul R Young, Daniel Watterson, Herbert R Treutlein, Jun Zeng
We have previously described a method to predict antigenic epitopes on proteins recognized by specific antibodies. Here we have applied this method to identify epitopes on the NS1 proteins of the four Dengue virus serotypes (DENV1-4) that are bound by a small panel of monoclonal antibodies 1H7.4, 1G5.3 and Gus2. Several epitope regions were predicted for these antibodies and these were found to reflect the experimentally observed reactivities. The known binding epitopes on DENV2 for the antibodies 1H7.4 and 1G5...
April 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28393899/increased-serum-hyaluronic-acid-and-heparan-sulfate-in-dengue-fever-association-with-plasma-leakage-and-disease-severity
#13
Tommy Hing-Cheung Tang, Sylvie Alonso, Lisa Fong-Poh Ng, Tun-Linn Thein, Vincent Jun-Xiong Pang, Yee-Sin Leo, David Chien-Boon Lye, Tsin-Wen Yeo
Plasma leakage is a major pathogenic mechanism of severe dengue, but the etiology remains unclear. The association between endothelial glycocalyx integrity and vascular permeability in older adults with dengue has not been evaluated. A prospective cohort study of adults with undifferentiated fever screened for dengue by RT-PCR or NS1 antigen testing was performed. Patients were assessed daily while symptomatic and at convalescence. Serum hyaluronic acid (HA), heparan sulfate (HS) and selected cytokines (TNF-α, IL-6, IL-10) were measured on enrollment and convalescence...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28389145/serodiagnosis-of-dengue-virus-infection-using-commercially-available-antibody-and-ns1-antigen-elisas
#14
D Granger, Y S Leo, L K Lee, E S Theel
Accuracy of the InBios DENV Detect IgM, IgG and NS1 antigen (Ag) ELISAs (Seattle, WA) for detection of dengue virus (DENV) infection were evaluated using 100 retrospectively selected sera from acutely febrile patients presenting to a Singapore hospital. The InBios DENV NS1, IgM and IgG ELISAs had an overall sensitivity of 83.6%, 40% and 58.2% and an overall specificity of 97.8%, 97.8% and 55.6%, respectively. Simultaneous testing for NS1 and IgM-antibodies yielded a sensitivity and specificity of 85.5% and 95...
March 30, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28388487/characterization-of-virus-specific-vesicles-assembled-by-west-nile-virus-non-structural-proteins
#15
Li Yu, Kazuyo Takeda, Yamei Gao
Flavivirus genome encodes seven non-structural proteins (NSPs) and these NSPs are believed to be involved in their genomic RNA replication, of which the mechanism is unclear. We find that West Nile virus (WNV) NSPs were capable of self-assembling membranous vesicles in cells, which are composed of the host endoplasmic reticulum membrane integrated with viral NS1 and NS4A, and possibly NS2A. The vesicles can further organize into replication complex (RC)-associated vesicles which combine both the vesicle and predicted RC components...
June 2017: Virology
https://www.readbyqxmd.com/read/28381638/antibody-epitopes-identified-in-critical-regions-of-dengue-virus-nonstructural-1-protein-in-mouse-vaccination-and-natural-human-infections
#16
Tomer Hertz, P Robert Beatty, Zachary MacMillen, Sarah S Killingbeck, Chunling Wang, Eva Harris
Dengue is a global public health problem and is caused by four dengue virus (DENV) serotypes (DENV1-4). A major challenge in dengue vaccine development is that cross-reactive anti-DENV Abs can be protective or potentially increase disease via Ab-dependent enhancement. DENV nonstructural protein 1 (NS1) has long been considered a vaccine candidate as it avoids Ab-dependent enhancement. In this study, we evaluated survival to challenge in a lethal DENV vascular leak model in mice immunized with NS1 combined with aluminum and magnesium hydroxide, monophosphoryl lipid A + AddaVax, or Sigma adjuvant system+CpG DNA, compared with mice infected with a sublethal dose of DENV2 and mice immunized with OVA (negative control)...
April 5, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28381608/sensitivity-and-kinetics-of-a-ns1-based-zika-virus-elisa-in-zika-infected-travelers-from-israel-czech-republic-italy-belgium-germany-and-chile
#17
Yaniv Lustig, Hana Zelena, Giulietta Venturi, Marjan Van Esbroeck, Camilla Rothe, Cecilia Perret, Ravit Koren, Shiri Katz-Likvornik, Ella Mendelson, Eli Schwartz
Serological diagnosis of Zika Virus is challenging due to high cross-reactivity of Zika virus with other flavivirus antibodies. Recently, a Zika-NS1 based ELISA was developed and shown to be highly specific for Zika antibodies detection; however, sensitivity was evaluated for only a small number of confirmed Zika infected patients. In this study we measured the sensitivity and kinetics of Zika IgM and IgG antibodies by the Zika-NS1 based ELISA in 105 samples from 63 returning-travelers infected by Zika virus (proven by PCR or neutralization assay) from Israel, Czech-Republic, Italy, Belgium, Germany and Chile...
April 5, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28373913/zika-virus-evades-interferon-mediated-antiviral-response-through-the-co-operation-of-multiple-nonstructural-proteins-in-vitro
#18
Yaoxing Wu, Qingxiang Liu, Jie Zhou, Weihong Xie, Cheng Chen, Zefang Wang, Haitao Yang, Jun Cui
Type I interferon (IFN) serves as the first line of defense against invading pathogens. Inhibition of IFN-triggered signaling cascade by Zika virus (ZIKV) plays a critical role for ZIKV to evade antiviral responses from host cells. Here we demonstrate that ZIKV nonstructural proteins NS1, NS4B and NS2B3 inhibit the induction of IFN and downstream IFN-stimulated genes through diverse strategies. NS1 and NS4B of ZIKV inhibit IFNβ signaling at TANK-binding kinase 1 level, whereas NS2B-NS3 of ZIKV impairs JAK-STAT signaling pathway by degrading Jak1 and reduces virus-induced apoptotic cell death...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28370088/expression-of-surface-bound-non-structural-1-ns1-protein-of-influenza-virus-a-h5n1-on-lactobacillus-casei-strain-c1
#19
Toong Seng Tan, Sharifah Syed Hassan, Wei Boon Yap
The study aimed to construct a recombinant Lactobacillus casei (L. casei) expressing the non-structural (NS) 1 protein of influenza A virus H5N1 on its cell wall. The NS1 gene was first amplified and fused to the pSGANC332 expression plasmid. The NS1 protein expression was carried out by L. casei strain C1. PCR screening and DNA sequencing confirmed the presence of recombinant pSG-NS1-ANC332 plasmid in L. casei. The plasmid was stably maintained (98.94±1.65%) by the bacterium within the first 20 generations without selective pressure...
April 2, 2017: Letters in Applied Microbiology
https://www.readbyqxmd.com/read/28368102/the-molecular-mechanisms-underlying-the-hijack-of-host-proteins-by-the-1918-spanish-influenza-virus
#20
Qingliang Shen, Danyun Zeng, Baoyu Zhao, Veer S Bhatt, Pingwei Li, Jae-Hyun Cho
The 1918 Spanish influenza A virus (IAV) caused one of the most serious pandemics in history. The nonstructural protein 1 (NS1) of the 1918 IAV hijacks the interaction between human CrkII and JNK1. Little is, however, known about its molecular mechanism. Here, we performed X-ray crystallography, NMR relaxation dispersion experiment, and fluorescence spectroscopy to determine the structural, kinetic, and thermodynamic mechanisms underlying the hijacking of CrkII by 1918 IAV NS1. We observed that the interaction between a proline-rich motif in NS1 and the N-terminal SH3 domain of CrkII displays strikingly rapid kinetics and exceptionally high affinity with 100-fold faster kon and 3,300-fold lower Kd compared to those for the CrkII-JNK1 interaction...
April 3, 2017: ACS Chemical Biology
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