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https://www.readbyqxmd.com/read/28324177/a-detailed-analysis-of-codon-usage-patterns-and-influencing-factors-in-zika-virus
#1
Niraj K Singh, Anuj Tyagi
Recent outbreaks of Zika virus (ZIKV) in Africa, Latin America, Europe, and Southeast Asia have resulted in serious health concerns. To understand more about evolution and transmission of ZIKV, detailed codon usage analysis was performed for all available strains. A high effective number of codons (ENC) value indicated the presence of low codon usage bias in ZIKV. The effect of mutational pressure on codon usage bias was confirmed by significant correlations between nucleotide compositions at third codon positions and ENCs...
March 21, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28322690/biologic-evidence-required-for-zika-disease-enhancement-by-dengue-antibodies
#2
Scott B Halstead
The sudden appearance of overt human Zika virus infections that cross the placenta to damage fetal tissues, target sexual organs, and are followed in some instances by Guillain-Barré syndrome raises questions regarding whether these outcomes are caused by genetic mutations or if prior infection by other flaviviruses affects disease outcome. Because dengue and Zika viruses co-circulate in the urban Aedes aegypti mosquito-human cycle, a logical question, as suggested by in vitro data, is whether dengue virus infections result in antibody-dependent enhancement of Zika virus infections...
April 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28289159/cutting-edge-innate-immune-augmenting-vesicular-stomatitis-virus-expressing-zika-virus-proteins-confers-protective-immunity
#3
Dillon Betancourt, Nina M G P de Queiroz, Tianli Xia, Jeonghyun Ahn, Glen N Barber
Zika virus (ZIKV) has become a serious public health concern because of its link to brain damage in developing human fetuses. Recombinant vesicular stomatitis virus (rVSV) was shown to be a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. In this study, we generated rVSVs (wild-type and attenuated VSV with mutated matrix protein [VSVm] versions) that express either the full length ZIKV envelope protein (ZENV) alone or include the ZENV precursor to the membrane protein upstream of the envelope protein, and our rVSV-ZIKV constructs showed efficient immunogenicity in murine models...
March 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28275585/mutational-pressure-in-zika-virus-local-adar-editing-areas-associated-with-pauses-in-translation-and-replication
#4
Vladislav V Khrustalev, Tatyana A Khrustaleva, Nitin Sharma, Rajanish Giri
Zika virus (ZIKV) spread led to the recent medical health emergency of international concern. Understanding the variations in virus system is of utmost need. Using available complete sequences of ZIKV we estimated directions of mutational pressure along the length of consensus sequences of three lineages of the virus. Results showed that guanine usage is growing in ZIKV RNA plus strand due to adenine to guanine transitions, while adenine usage is growing due to cytosine to adenine transversions. Especially high levels of guanine have been found in two-fold degenerated sites of certain areas of RNA plus strand with high amount of secondary structure...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28264033/dengue-virus-genomic-variation-associated-with-mosquito-adaptation-defines-the-pattern-of-viral-non-coding-rnas-and-fitness-in-human-cells
#5
Claudia V Filomatori, Juan M Carballeda, Sergio M Villordo, Sebastian Aguirre, Horacio M Pallarés, Ana M Maestre, Irma Sánchez-Vargas, Carol D Blair, Cintia Fabri, Maria A Morales, Ana Fernandez-Sesma, Andrea V Gamarnik
The Flavivirus genus includes a large number of medically relevant pathogens that cycle between humans and arthropods. This host alternation imposes a selective pressure on the viral population. Here, we found that dengue virus, the most important viral human pathogen transmitted by insects, evolved a mechanism to differentially regulate the production of viral non-coding RNAs in mosquitos and humans, with a significant impact on viral fitness in each host. Flavivirus infections accumulate non-coding RNAs derived from the viral 3'UTRs (known as sfRNAs), relevant in viral pathogenesis and immune evasion...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28222903/modified-mrna-vaccines-protect-against-zika-virus-infection
#6
Justin M Richner, Sunny Himansu, Kimberly A Dowd, Scott L Butler, Vanessa Salazar, Julie M Fox, Justin G Julander, William W Tang, Sujan Shresta, Theodore C Pierson, Giuseppe Ciaramella, Michael S Diamond
The emergence of ZIKV infection has prompted a global effort to develop safe and effective vaccines. We engineered a lipid nanoparticle (LNP) encapsulated modified mRNA vaccine encoding wild-type or variant ZIKV structural genes and tested immunogenicity and protection in mice. Two doses of modified mRNA LNPs encoding prM-E genes that produced virus-like particles resulted in high neutralizing antibody titers (∼1/100,000) that protected against ZIKV infection and conferred sterilizing immunity. To offset a theoretical concern of ZIKV vaccines inducing antibodies that cross-react with the related dengue virus (DENV), we designed modified prM-E RNA encoding mutations destroying the conserved fusion-loop epitope in the E protein...
February 16, 2017: Cell
https://www.readbyqxmd.com/read/28207910/a-single-mutation-in-the-envelope-protein-modulates-flavivirus-antigenicity-stability-and-pathogenesis
#7
Leslie Goo, Laura A VanBlargan, Kimberly A Dowd, Michael S Diamond, Theodore C Pierson
The structural flexibility or 'breathing' of the envelope (E) protein of flaviviruses allows virions to sample an ensemble of conformations at equilibrium. The molecular basis and functional consequences of virus conformational dynamics are poorly understood. Here, we identified a single mutation at residue 198 (T198F) of the West Nile virus (WNV) E protein domain I-II hinge that regulates virus breathing. The T198F mutation resulted in a ~70-fold increase in sensitivity to neutralization by a monoclonal antibody targeting a cryptic epitope in the fusion loop...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28198446/a-mutation-identified-in-neonatal-microcephaly-destabilizes-zika-virus-ns1-assembly-in-vitro
#8
Deping Wang, Cheng Chen, Shengnan Liu, Han Zhou, Kailin Yang, Qi Zhao, Xiaoyun Ji, Chen Chen, Wei Xie, Zefang Wang, Li-Zhi Mi, Haitao Yang
An unprecedented epidemic of Zika virus (ZIKV) infection had spread to South and Central America. ZIKV infection was recently confirmed by CDC (the Centers for Disease Control and Prevention) to cause neonatal microcephaly, which posed a significant public health emergency of international concern. No specific vaccines or drugs are currently available to fight ZIKV infection. ZIKV nonstructural protein 1 (NS1) plays an essential role in viral replication and immune evasion. We determined the crystal structure of ZIKV NS1172-352, which forms a head-to-head, symmetric dimer with a unique 14-stranded β-ladder conserved among flaviviruses...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196656/a-cdna-clone-launched-platform-for-high-yield-production-of-inactivated-zika-vaccine
#9
Yujiao Yang, Chao Shan, Jing Zou, Antonio E Muruato, Diniz Nunes Bruno, Barbosa de Almeida Medeiros Daniele, Pedro F C Vasconcelos, Shannan L Rossi, Scott C Weaver, Xuping Xie, Pei-Yong Shi
A purified inactivated vaccine (PIV) using the Zika virus (ZIKV) Puerto Rico strain PRVABC59 showed efficacy in monkeys, and is currently in a phase I clinical trial. High-yield manufacture of this PIV is essential for its development and vaccine access. Here we report an infectious cDNA clone-launched platform to maximize its yield. A single NS1 protein substitution (K265E) was identified to increase ZIKV replication on Vero cells (a cell line approved for vaccine production) for both Cambodian FSS13025 and Puerto Rico PRVABC59 strains...
February 6, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28187780/levels-of-insecticide-resistance-to-deltamethrin-malathion-and-temephos-and-associated-mechanisms-in-aedes-aegypti-mosquitoes-from-the-guadeloupe-and-saint-martin-islands-french-west-indies
#10
Daniella Goindin, Christelle Delannay, Andric Gelasse, Cédric Ramdini, Thierry Gaude, Frédéric Faucon, Jean-Philippe David, Joël Gustave, Anubis Vega-Rua, Florence Fouque
BACKGROUND: In the Guadeloupe and Saint Martin islands, Aedes aegypti mosquitoes are the only recognized vectors of dengue, chikungunya, and Zika viruses. For around 40 years, malathion was used as a mosquito adulticide and temephos as a larvicide. Since the European Union banned the use of these two insecticide molecules in the first decade of the 21st century, deltamethrin and Bacillus thuringiensis var. israelensis are the remaining adulticide and larvicide, respectively, used in Guadeloupe...
February 10, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28174309/understanding-zika-virus-stability-and-developing-a-chimeric-vaccine-through-functional-analysis
#11
Xuping Xie, Yujiao Yang, Antonio E Muruato, Jing Zou, Chao Shan, Bruno T D Nunes, Daniele B A Medeiros, Pedro F C Vasconcelos, Scott C Weaver, Shannan L Rossi, Pei-Yong Shi
Compared with other flaviviruses, Zika virus (ZIKV) is uniquely associated with congenital diseases in pregnant women. One recent study reported that (i) ZIKV has higher thermostability than dengue virus (DENV [a flavivirus closely related to ZIKV]), which might contribute to the disease outcome; (ii) the higher thermostability of ZIKV could arise from an extended loop structure in domain III of the viral envelope (E) protein and an extra hydrogen-bond interaction between E molecules (V. A. Kostyuchenko, E...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28102842/zika-virus-elicits-p53-activation-and-genotoxic-stress-in-human-neural-progenitors-similar-to-mutations-involved-in-severe-forms-of-genetic-microcephaly-and-p53
#12
Vincent El Ghouzzi, Federico T Bianchi, Ivan Molineris, Bryan C Mounce, Gaia E Berto, Malgorzata Rak, Sophie Lebon, Laetitia Aubry, Chiara Tocco, Marta Gai, Alessandra Ma Chiotto, Francesco Sgrò, Gianmarco Pallavicini, Etienne Simon-Loriere, Sandrine Passemard, Marco Vignuzzi, Pierre Gressens, Ferdinando Di Cunto
No abstract text is available yet for this article.
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28098253/the-clinically-approved-antiviral-drug-sofosbuvir-inhibits-zika-virus-replication
#13
Carolina Q Sacramento, Gabrielle R de Melo, Caroline S de Freitas, Natasha Rocha, Lucas Villas Bôas Hoelz, Milene Miranda, Natalia Fintelman-Rodrigues, Andressa Marttorelli, André C Ferreira, Giselle Barbosa-Lima, Juliana L Abrantes, Yasmine Rangel Vieira, Mônica M Bastos, Eduardo de Mello Volotão, Estevão Portela Nunes, Diogo A Tschoeke, Luciana Leomil, Erick Correia Loiola, Pablo Trindade, Stevens K Rehen, Fernando A Bozza, Patrícia T Bozza, Nubia Boechat, Fabiano L Thompson, Ana M B de Filippis, Karin Brüning, Thiago Moreno L Souza
Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28087772/possible-roles-of-new-mutations-shared-by-asian-and-american-zika-viruses
#14
Shozo Yokoyama, William T Starmer
Originating in Africa, the Zika virus (ZIKV) has spread to Asia, Pacific Islands and now to the Americas and beyond. Since the first isolation in 1947, ZIKV strains have been sampled at various times in the last 69 years, but this history has not been reflected in studying the patterns of mutation accumulation in their genomes. Implementing the viral history, we show that the ZIKV ancestor appeared sometime in 1930-1945 and, at that point, its mutation rate was probably less than 0.2 × 10(-3)/nucleotide site/year and subsequently increased significantly in most of its descendants...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27993855/obatoclax-inhibits-alphavirus-membrane-fusion-by-neutralizing-the-acidic-environment-of-endocytic-compartments
#15
Finny S Varghese, Kai Rausalu, Marika Hakanen, Sirle Saul, Beate M Kümmerer, Petri Susi, Andres Merits, Tero Ahola
As new pathogenic viruses continue to emerge, it is paramount to have intervention strategies that target a common denominator in these pathogens. The fusion of viral and cellular membranes during viral entry is one such process that is used by many pathogenic viruses, including chikungunya virus, West Nile virus, and influenza virus. Obatoclax, a small-molecule antagonist of the Bcl-2 family of proteins, was previously determined to have activity against influenza A virus and also Sindbis virus. Here, we report it to be active against alphaviruses, like chikungunya virus (50% effective concentration [EC50] = 0...
March 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27934765/zika-virus-produces-noncoding-rnas-using-a-multi-pseudoknot-structure-that-confounds-a-cellular-exonuclease
#16
Benjamin M Akiyama, Hannah M Laurence, Aaron R Massey, David A Costantino, Xuping Xie, Yujiao Yang, Pei-Yong Shi, Jay C Nix, J David Beckham, Jeffrey S Kieft
The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonuclease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses...
December 2, 2016: Science
https://www.readbyqxmd.com/read/27930336/resistance-mutation-conserved-between-insects-and-mites-unravels-the-benzoylurea-insecticide-mode-of-action-on-chitin-biosynthesis
#17
Vassilis Douris, Denise Steinbach, Rafaela Panteleri, Ioannis Livadaras, John Anthony Pickett, Thomas Van Leeuwen, Ralf Nauen, John Vontas
Despite the major role of chitin biosynthesis inhibitors such as benzoylureas (BPUs) in the control of pests in agricultural and public health for almost four decades, their molecular mode of action (MoA) has in most cases remained elusive. BPUs interfere with chitin biosynthesis and were thought to interact with sulfonylurea receptors that mediate chitin vesicle transport. Here, we uncover a mutation (I1042M) in the chitin synthase 1 (CHS1) gene of BPU-resistant Plutella xylostella at the same position as the I1017F mutation reported in spider mites that confers etoxazole resistance...
December 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27893824/analysis-of-synonymous-codon-usage-bias-of-zika-virus-and-its-adaption-to-the-hosts
#18
Hongju Wang, Siqing Liu, Bo Zhang, Wenqiang Wei
Zika virus (ZIKV) is a mosquito-borne virus (arbovirus) in the family Flaviviridae, and the symptoms caused by ZIKV infection in humans include rash, fever, arthralgia, myalgia, asthenia and conjunctivitis. Codon usage bias analysis can reveal much about the molecular evolution and host adaption of ZIKV. To gain insight into the evolutionary characteristics of ZIKV, we performed a comprehensive analysis on the codon usage pattern in 46 ZIKV strains by calculating the effective number of codons (ENc), codon adaptation index (CAI), relative synonymous codon usage (RSCU), and other indicators...
2016: PloS One
https://www.readbyqxmd.com/read/27886338/frequency-of-the-val1016ile-mutation-on-the-kdr-gene-in-aedes-aegypti-diptera-culicidae-in-south-brazil
#19
M L Collet, C Frizzo, E Orlandin, L D P Rona, J C Nascimento, M A E Montano, G A Müller, G Wagner
Recently, the number of Aedes aegypti foci has increased in west of Santa Catarina, south Brazil, which has increased concern regarding mosquito-borne disease outbreaks such as dengue fever, Zika virus, and chikungunya. Therefore, it is important to monitor genetic resistance to insecticides through "knockdown resistance". Homozygosity (Ile/Ile) at position 1016 in the coding region of a voltage-dependent sodium channel gene (Nav) may induce resistance to pyrethroid insecticides. We evaluated the frequency of these alleles in A...
November 21, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27881148/susceptibility-profile-and-metabolic-mechanisms-involved-in-aedes-aegypti-and-aedes-albopictus-resistant-to-ddt-and-deltamethrin-in-the-central-african-republic
#20
Carine Ngoagouni, Basile Kamgang, Cécile Brengues, Gildas Yahouedo, Christophe Paupy, Emmanuel Nakouné, Mirdad Kazanji, Fabrice Chandre
BACKGROUND: Aedes aegypti and Ae. albopictus are the main epidemic vectors of dengue, chikungunya and Zika viruses worldwide. Their control during epidemics relies mainly on control of larvae and adults with insecticides. Unfortunately, loss of susceptibility of both species to several insecticide classes limits the efficacy of interventions. In Africa, where Aedes-borne viruses are of growing concern, few data are available on resistance to insecticides. To fill this gap, we assessed the susceptibility to insecticides of Ae...
November 24, 2016: Parasites & Vectors
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