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https://www.readbyqxmd.com/read/28422757/cross-reactive-dengue-human-monoclonal-antibody-prevents-severe-pathologies-and-death-from-zika-virus-infections
#1
Yiu-Wing Kam, Cheryl Yi-Pin Lee, Teck-Hui Teo, Shanshan W Howland, Siti Naqiah Amrun, Fok-Moon Lum, Peter See, Nicholas Qing-Rong Kng, Roland G Huber, Mei-Hui Xu, Heng-Liang Tan, Andre Choo, Sebastian Maurer-Stroh, Florent Ginhoux, Katja Fink, Cheng-I Wang, Lisa F P Ng, Laurent Rénia
Zika virus (ZIKV) infections have been linked with neurological complications and congenital Zika syndrome. Given the high level of homology between ZIKV and the related flavivirus dengue virus (DENV), we investigated the level of cross-reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs showed binding to ZIKV virions, with several exhibiting neutralizing capacities against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved fusion-loop peptide, a conformation-specific epitope on the E monomer, and a quaternary epitope on the virion surface...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28422157/detection-of-a-new-pyrethroid-resistance-mutation-v410l-in-the-sodium-channel-of-aedes-aegypti-a-potential-challenge-for-mosquito-control
#2
Khalid Haddi, Hudson V V Tomé, Yuzhe Du, Wilson R Valbon, Yoshiko Nomura, Gustavo F Martins, Ke Dong, Eugênio E Oliveira
The yellow fever mosquito, Aedes aegypti, particularly in Neotropical regions, is the principal vector of dengue, yellow fever, Zika and Chikungunya viruses. Pyrethroids remain one of the most used insecticides to control Aedes mosquitoes, despite the development of pyrethroid resistance in many mosquito populations worldwide. Here, we report a Brazilian strain of A. aegypti with high levels (approximately 100-60,000 fold) of resistance to both type I and type II pyrethroids. We detected two mutations (V410L and F1534C) in the sodium channel from this resistant strain...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28408723/nucleic-acid-detection-with-crispr-cas13a-c2c2
#3
Jonathan S Gootenberg, Omar O Abudayyeh, Jeong Wook Lee, Patrick Essletzbichler, Aaron J Dy, Julia Joung, Vanessa Verdine, Nina Donghia, Nichole M Daringer, Catherine A Freije, Cameron Myhrvold, Roby P Bhattacharyya, Jonathan Livny, Aviv Regev, Eugene V Koonin, Deborah T Hung, Pardis C Sabeti, James J Collins, Feng Zhang
Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA-targeting CRISPR effector Cas13a (previously known as C2c2) exhibits a "collateral effect" of promiscuous RNAse activity upon target recognition. We combine the collateral effect of Cas13a with isothermal amplification to establish a CRISPR-based diagnostic (CRISPR-Dx), providing rapid DNA or RNA detection with attomolar sensitivity and single-base mismatch specificity...
April 13, 2017: Science
https://www.readbyqxmd.com/read/28396522/de-novo-assembly-of-viral-quasispecies-using-overlap-graphs
#4
Jasmijn A Baaijens, Amal Zine El Aabidine, Eric Rivals, Alexander Schönhuth
A viral quasispecies, the ensemble of viral strains populating an infected person, can be highly diverse. For optimal assessment of virulence, pathogenesis, and therapy selection, determining the haplotypes of the individual strains can play a key role. As many viruses are subject to high mutation and recombination rates, high-quality reference genomes are often not available at the time of a new disease outbreak. We present SAVAGE, a computational tool for reconstructing individual haplotypes of intra-host virus strains without the need for a high-quality reference genome...
April 10, 2017: Genome Research
https://www.readbyqxmd.com/read/28351337/zika-virus-ns5-protein-potential-inhibitors-an-enhanced-in-silico-approach-in-drug-discovery
#5
Pritika Ramharack, Mahmoud E S Soliman
The re-emerging Zika virus is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus has already been linked to irreversible chronic central nervous system (CNS) conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors...
March 29, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28347352/combined-target-site-kdr-mutations-play-a-primary-role-in-highly-pyrethroid-resistant-phenotypes-of-aedes-aegypti-from-saudi-arabia
#6
Ashwaq M Al Nazawi, Jabir Aqili, Mohammed Alzahrani, Philip J McCall, David Weetman
BACKGROUND: Pyrethroid resistance is a threat to effective vector control of Aedes aegypti, the vector of dengue, Zika and other arboviruses, but there are many major knowledge gaps on the mechanisms of resistance. In Jeddah and Makkah, the principal dengue-endemic areas of Saudi Arabia, pyrethroids are used widely for Ae. aegypti control but information about resistance remains sparse, and the underlying genetic basis is unknown. Findings from an ongoing study in this internationally significant area are reported here...
March 27, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28347326/first-report-of-the-phe1534cys-kdr-mutation-in-natural-populations-of-aedes-albopictus-from-brazil
#7
Oscar Alexander Aguirre-Obando, Ademir Jesus Martins, Mário Antônio Navarro-Silva
BACKGROUND: Knockdown resistance (kdr), caused by alterations in the voltage-gated sodium channel (NaV), is one of the mechanisms responsible for pyrethroid (PY) resistance. In the Asian tiger mosquito, Aedes albopictus, at least four different mutations were described in the IIIS6 NaV segment in populations from Asia, North America and Europe. In contrast, in Aedes aegypti at least 12 non-synonymous mutations have been reported at nine different codons, mostly in the IIS6 and IIIS6 NaV segments...
March 27, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28324177/a-detailed-analysis-of-codon-usage-patterns-and-influencing-factors-in-zika-virus
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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...
March 9, 2017: Cell
https://www.readbyqxmd.com/read/28207910/a-single-mutation-in-the-envelope-protein-modulates-flavivirus-antigenicity-stability-and-pathogenesis
#14
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
#15
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
#16
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...
March 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
#17
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
#18
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
#19
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
#20
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
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