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https://www.readbyqxmd.com/read/28222903/modified-mrna-vaccines-protect-against-zika-virus-infection
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
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
#7
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
#8
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
#9
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
#10
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, influenza virus etc. Obatoclax, a small-molecule antagonist of the Bcl-2 family of proteins was previously determined to be antiviral against influenza A virus and also Sindbis virus. Here, we report it to be active against alphaviruses like chikungunya virus (EC50 = 0...
December 19, 2016: 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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/27870689/zika-virus-and-diagnostics
#16
Claudia Raja Gabaglia
PURPOSE OF REVIEW: The purpose of this review is to present what is known about the Zika virus (ZIKV) at the time of writing this review. The viral structure and its phylogeny, as well as the limitations of current available techniques used for diagnosis, are discussed. RECENT FINDINGS: Crystallography and cryo-electron microscopy of the whole ZIKV, or a few of its proteins, are confirming its overall antigenic relatedness to other flaviviruses. Sequencing has revealed its dynamic genetic variation and has placed the Western cluster of Zika isolates within the Asian phylogenic tree...
February 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/27869391/-first-report-of-the-f1534c-mutation-associated-with-cross-resistance-to-ddt-and-pyrethroids-in-aedes-aegypti-from-colombia
#17
María Claudia Atencia, María De Jesús Pérez, María Cristina Jaramillo, Sandy Milena Caldera, Suljey Cochero, Eduar Elías Bejarano
The main strategy for the control of Aedes aegypti, vector of dengue, chikungunya and Zika viruses, is based on the use of insecticides to reduce its populations. However, their use has led to insect resistance to these chemicals. Objective: To determine the presence of the F1534C mutation associated with cross-resistance to DDT and pyrethroids in A. aegypti in Sincelejo, Colombia. Materials and methods: We studied nine specimens of A. aegypti that showed resistance to lambdacyhalothrin in bioassays developed by the Secretaría de Salud de Sucre...
September 1, 2016: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/27809228/sodium-channel-mutations-and-pyrethroid-resistance-in-aedes-aegypti
#18
REVIEW
Yuzhe Du, Yoshiko Nomura, Boris S Zhorov, Ke Dong
Pyrethroid insecticides are widely used to control insect pests and human disease vectors. Voltage-gated sodium channels are the primary targets of pyrethroid insecticides. Mutations in the sodium channel have been shown to be responsible for pyrethroid resistance, known as knockdown resistance (kdr), in various insects including mosquitoes. In Aedes aegypti mosquitoes, the principal urban vectors of dengue, zika, and yellow fever viruses, multiple single nucleotide polymorphisms in the sodium channel gene have been found in pyrethroid-resistant populations and some of them have been functionally confirmed to be responsible for kdr in an in vitro expression system, Xenopus oocytes...
October 31, 2016: Insects
https://www.readbyqxmd.com/read/27805221/analysis-of-worldwide-sequence-mutations-in-zika-virus-proteins-e-ns1-ns3-and-ns5-from-a-structural-point-of-view
#19
C F Baez, V A Barel, A M T de Souza, C R Rodrigues, R B Varella, N Cirauqui
Zika virus (ZIKV) is an emergent arbovirus that has attracted attention in the last year as a possible causative agent of congenital malformation; it shows a remarkably increased microcephaly risk during otherwise healthy pregnancies. We present here an analysis of all ZIKV sequences available in Genbank up to April 2016, studying the mutations in the whole polyprotein and their possible structural implications for the proteins E, NS1, NS3 and NS5. This study suggests that microcephaly is not a consequence of any particular amino acid substitution but, conceivably, is a feature of ZIKV itself...
December 20, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27787521/zika-virus-elicits-p53-activation-and-genotoxic-stress-in-human-neural-progenitors-similar-to-mutations-involved-in-severe-forms-of-genetic-microcephaly-and-p53
#20
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
Epidemiological evidence from the current outbreak of Zika virus (ZIKV) and recent studies in animal models indicate a strong causal link between ZIKV and microcephaly. ZIKV infection induces cell-cycle arrest and apoptosis in proliferating neural progenitors. However, the mechanisms leading to these phenotypes are still largely obscure. In this report, we explored the possible similarities between transcriptional responses induced by ZIKV in human neural progenitors and those elicited by three different genetic mutations leading to severe forms of microcephaly in mice...
October 27, 2016: Cell Death & Disease
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