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https://www.readbyqxmd.com/read/28542603/a-conformational-switch-high-throughput-screening-assay-and-allosteric-inhibition-of-the-flavivirus-ns2b-ns3-protease
#1
Matthew Brecher, Zhong Li, Binbin Liu, Jing Zhang, Cheri A Koetzner, Adham Alifarag, Susan A Jones, Qishan Lin, Laura D Kramer, Hongmin Li
The flavivirus genome encodes a single polyprotein precursor requiring multiple cleavages by host and viral proteases in order to produce the individual proteins that constitute an infectious virion. Previous studies have revealed that the NS2B cofactor of the viral NS2B-NS3 heterocomplex protease displays a conformational dynamic between active and inactive states. Here, we developed a conformational switch assay based on split luciferase complementation (SLC) to monitor the conformational change of NS2B and to characterize candidate allosteric inhibitors...
May 25, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28539440/uncovering-the-repertoire-of-endogenous-flaviviral-elements-in-aedes-mosquito-genomes
#2
Yasutsugu Suzuki, Lionel Frangeul, Laura B Dickson, Hervé Blanc, Yann Verdier, Joelle Vinh, Louis Lambrechts, Maria-Carla Saleh
Endogenous viral elements derived from non-retroviral RNA viruses were described in various animal genomes. Whether they have a biological function such as host immune protection against related viruses is a field of intense study. Here, we investigated the repertoire of endogenous flaviviral elements (EFVEs) in Aedes mosquitoes, the vectors of arboviruses such as dengue and chikungunya viruses. Previous studies identified three EFVEs from Ae. albopictus and one from Ae. aegypti cell lines. However, in-depth characterization of EFVEs in wild-type mosquito populations and individuals in vivo has not been performed...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28525510/zika-virus-obstetric-and-pediatric-anesthesia-considerations
#3
Jacqueline L Tutiven, Benjamin T Pruden, James S Banks, Mario Stevenson, David J Birnbach
As of November 2016, the Florida Department of Health (FDH) and the Centers for Disease Control and Prevention have confirmed more than 4000 travel-related Zika virus (ZIKV) infections in the United States with >700 of those in Florida. There have been 139 cases of locally acquired infection, all occurring in Miami, Florida. Within the US territories (eg, Puerto Rico, US Virgin Islands), >30,000 cases of ZIKV infection have been reported. The projected number of individuals at risk for ZIKV infection in the Caribbean and Latin America approximates 5 million...
June 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28515302/transposon-mutagenesis-of-the-zika-virus-genome-highlights-regions-essential-for-rna-replication-and-restricted-for-immune-evasion
#4
Benjamin O Fulton, David Sachs, Megan C Schwarz, Peter Palese, Matthew J Evans
The molecular constraints affecting Zika virus (ZIKV) evolution are not well understood. To investigate ZIKV genetic flexibility, we used transposon mutagenesis to add 15-nucleotide insertions throughout the MR766 ZIKV genome and subsequently deep sequenced the viable mutants. Few ZIKV insertion mutants replicated, which likely reflects a high degree of functional constraints on the genome. The NS1 gene exhibited distinct mutational tolerances at different stages of the screen. This result may define regions of the NS1 protein that are required for the different stages of the viral life cycle...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28507114/antiviral-activity-of-nordihydroguaiaretic-acid-and-its-derivative-tetra-o-methyl-nordihydroguaiaretic-acid-against-west-nile-virus-and-zika-virus
#5
Teresa Merino-Ramos, Nereida Jiménez de Oya, Juan-Carlos Saiz, Miguel A Martín-Acebes
Flaviviruses are positive strand RNA viruses distributed all over the world that infect millions of people every year, and for which no specific antiviral agents have been approved. These viruses include the mosquito-borne West Nile virus (WNV) responsible for outbreaks of meningitis and encephalitis. Considering that nordihydroguaiaretic acid (NDGA) has been previously shown to inhibit the multiplication of the related dengue virus and hepatitis C virus, we have evaluated the effect of NDGA, and its methylated derivative tetra-O-methyl nordihydroguaiaretic (M4N), on the infection of WNV...
May 15, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28506240/inhibitors-compounds-of-the-flavivirus-replication-process
#6
REVIEW
Leidy L García, Leonardo Padilla, Jhon C Castaño
Flaviviruses are small viruses with single-stranded RNA, which include the yellow fever virus, dengue virus, West Nile virus, Japanese encephalitis virus, tick-borne encephalitis virus, and Zika virus; and are causal agents of the most important emerging diseases that have no available treatment to date. In recent years, the strategy has focused on the development of replication inhibitors of these viruses designed to act mainly by affecting the activity of enzyme proteins, such as NS3 and NS5, which perform important functions in the viral replication process...
May 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28505571/re-evaluation-of-routine-dengue-virus-serology-in-travelers-in-the-era-of-zika-virus-emergence
#7
Maurits P A van Meer, Ramona Mögling, Janienne Klaasse, Felicity D Chandler, Suzan D Pas, Annemiek A van der Eijk, Marion P G Koopmans, Chantal B E M Reusken, Corine H GeurtsvanKessel
BACKGROUND: Diagnostic requests for both Zika virus (ZIKV) and dengue virus (DENV) infections in returning travelers have significantly increased during the recent ZIKV outbreak in the Americás. These flaviviruses have overlapping clinical syndromes and geographical distribution, but diagnostic differentiation is important because of different clinical consequences. As flaviviruses are known to have a short viremic period, diagnostics often rely on serological methods, which are challenging due to extensive cross-reactive antibodies...
May 3, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28505154/dissecting-the-human-serum-antibody-response-to-secondary-dengue-virus-infections
#8
Bhumi Patel, Patti Longo, Michael J Miley, Magelda Montoya, Eva Harris, Aravinda M de Silva
Dengue viruses (DENVs) are mosquito-borne flaviviruses and the causative agents of dengue fever and dengue hemorrhagic fever. As there are four serotypes of DENV (DENV1-4), people can be infected multiple times, each time with a new serotype. Primary infections stimulate antibodies that mainly neutralize the serotype of infection (type-specific), whereas secondary infections stimulate responses that cross-neutralize 2 or more serotypes. Previous studies have demonstrated that neutralizing antibodies induced by primary infections recognize tertiary and quaternary structure epitopes on the viral envelope (E) protein that are unique to each serotype...
May 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28499872/interaction-of-flavivirus-with-their-mosquito-vectors-and-their-impact-on-the-human-health-in-the-americas
#9
Anayansi Valderrama, Yamilka Diaz, Sandra López-Vergès
Some of the major arboviruses with public health importance, such as dengue, yellow fever, Zika and West Nile virus are mosquito-borne or mosquito-transmitted Flavivirus. Their principal vectors are from the family Culicidae, Aedes aegypti and Aedes albopictus being responsible of the urban cycles of dengue, Zika and yellow fever virus. These vectors are highly competent for transmission of many arboviruses. The genetic variability of the vectors, the environment and the viral diversity modulate the vector competence, in this context, it is important to determine which vector species is responsible of an outbreak in areas where many vectors coexist...
May 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28493351/human-zika-and-west-nile-virus-neurological-infections-what-is-the-difference
#10
REVIEW
Clayton A Wiley, Leila Chimelli
The recent epidemic of West Nile Virus (WNV) infection in the United States was associated with severe neurological disease in immunocompromised hosts, while the emergence of Zika virus infection in the Americas has been notable for an association with increased microcephaly in the fetuses of infected mothers. Rare autopsies of WNV infected humans have shown multiple organ involvement with a clear neurotropism. We have recently had the opportunity to examine the distribution of Zika virus in autopsies of newborns from infected pregnancies...
May 11, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28487557/humoral-cross-reactivity-between-zika-and-dengue-viruses-implications-for-protection-and-pathology
#11
REVIEW
Lalita Priyamvada, William Hudson, Rafi Ahmed, Jens Wrammert
Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that has recently caused extensive outbreaks in Central and South America and the Caribbean. Given its association with Guillain-Barré syndrome in adults and neurological and ocular malformities in neonates, ZIKV has become a pathogen of significant public health concern worldwide. ZIKV shares a considerable degree of genetic identity and structural homology with other flaviviruses, including dengue virus (DENV). In particular, the surface glycoprotein envelope (E), which is involved in viral fusion and entry and is therefore a chief target for neutralizing antibody responses, contains regions that are highly conserved between the two viruses...
May 10, 2017: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/28486135/recent-advances-in-human-flavivirus-vaccines
#12
REVIEW
Iris Scherwitzl, Juthathip Mongkolsapaja, Gavin Screaton
Dengue (DENV), West Nile (WNV) and Zika (ZIKV) viruses are mosquito-transmitted flaviviruses that cause thousands of human deaths and millions of illnesses each year. In the last decades, epidemic outbreaks of all three flaviviruses emerged and caused a major health and economical problem in many parts of the world. The increasing and expanding burden of flaviviruses has highlighted the need for effective human vaccines against all three viruses. This review provides an overview of the recent progress in DENV, WNV and ZIKV vaccines development with specific focus on candidates in human clinical development...
May 6, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28481883/in-a-randomized-trial-the-live-attenuated-tetravalent-dengue-vaccine-tv003-is-well-tolerated-and-highly-immunogenic-in-subjects-with-flavivirus-exposure-prior-to-vaccination
#13
Stephen S Whitehead, Anna P Durbin, Kristen K Pierce, Dan Elwood, Benjamin D McElvany, Ellen A Fraser, Marya P Carmolli, Cecilia M Tibery, Noreen A Hynes, Matthew Jo, Janece M Lovchik, Catherine J Larsson, Elena A Doty, Dorothy M Dickson, Catherine J Luke, Kanta Subbarao, Sean A Diehl, Beth D Kirkpatrick
ClinicalTrials.gov TV003.
May 8, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28475924/characterization-of-zika-virus-binding-and-enhancement-potential-of-a-large-panel-of-flavivirus-murine-monoclonal-antibodies
#14
Elinor Willis, Scott E Hensley
Zika viruses (ZIKVs) are circulating in parts of the world endemic for other flavivirus infections. Some cross-reactive antibodies (Abs) elicited by prior flavivirus exposures can bind to ZIKV and enhance infection of Fc receptor-bearing cells. Here, we measured ZIKV binding of 54 murine monoclonal Abs (mAbs) elicited by exposure with Dengue virus and West Nile virus antigens. We found that 8 of 54 mAbs recognized the envelope protein of ZIKV in conventional binding assays. These 8 cross-reactive mAbs have different specificities; most recognize the DI/II region of the envelope protein but one mAb recognized the DIII lateral ridge of the envelope protein...
May 2, 2017: Virology
https://www.readbyqxmd.com/read/28475892/recurrent-potent-human-neutralizing-antibodies-to-zika-virus-in-brazil-and-mexico
#15
Davide F Robbiani, Leonia Bozzacco, Jennifer R Keeffe, Ricardo Khouri, Priscilla C Olsen, Anna Gazumyan, Dennis Schaefer-Babajew, Santiago Avila-Rios, Lilian Nogueira, Roshni Patel, Stephanie A Azzopardi, Lion F K Uhl, Mohsan Saeed, Edgar E Sevilla-Reyes, Marianna Agudelo, Kai-Hui Yao, Jovana Golijanin, Harry B Gristick, Yu E Lee, Arlene Hurley, Marina Caskey, Joy Pai, Thiago Oliveira, Elsio A Wunder, Gielson Sacramento, Nivison Nery, Cibele Orge, Federico Costa, Mitermayer G Reis, Neena M Thomas, Thomas Eisenreich, Daniel M Weinberger, Antonio R P de Almeida, Anthony P West, Charles M Rice, Pamela J Bjorkman, Gustavo Reyes-Teran, Albert I Ko, Margaret R MacDonald, Michel C Nussenzweig
Antibodies to Zika virus (ZIKV) can be protective. To examine the antibody response in individuals who develop high titers of anti-ZIKV antibodies, we screened cohorts in Brazil and Mexico for ZIKV envelope domain III (ZEDIII) binding and neutralization. We find that serologic reactivity to dengue 1 virus (DENV1) EDIII before ZIKV exposure is associated with increased ZIKV neutralizing titers after exposure. Antibody cloning shows that donors with high ZIKV neutralizing antibody titers have expanded clones of memory B cells that express the same immunoglobulin VH3-23/VK1-5 genes...
May 4, 2017: Cell
https://www.readbyqxmd.com/read/28473729/broad-spectrum-agents-for-flaviviral-infections-dengue-zika-and-beyond
#16
REVIEW
Veaceslav Boldescu, Mira A M Behnam, Nikos Vasilakis, Christian D Klein
Infections with flaviviruses, such as dengue, West Nile virus and the recently re-emerging Zika virus, are an increasing and probably lasting global risk. This Review summarizes and comments on the opportunities for broad-spectrum agents that are active against multiple flaviviruses. Broad-spectrum activity is particularly desirable to prepare for the next flaviviral epidemic, which could emerge from as-yet unknown or neglected viruses. Potential molecular targets for broad-spectrum antiflaviviral compounds include viral proteins, such as the viral protease or polymerase, and host targets that are exploited by these viruses during entry and replication, including α-glucosidase and proteins involved in nucleoside biosynthesis...
May 5, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28471403/pathogenesis-and-inhibition-of-flaviviruses-from-a-carbohydrate-perspective
#17
REVIEW
So Young Kim, Bing Li, Robert J Linhardt
Flaviviruses are enveloped, positive single stranded ribonucleic acid (RNA) viruses with various routes of transmission. While the type and severity of symptoms caused by pathogenic flaviviruses vary from hemorrhagic fever to fetal abnormalities, their general mechanism of host cell entry is similar. All pathogenic flaviviruses, such as dengue virus, yellow fever virus, West Nile virus, Japanese encephalitis virus, and Zika virus, bind to glycosaminglycans (GAGs) through the putative GAG binding sites within their envelope proteins to gain access to the surface of host cells...
May 4, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28469032/rapid-and-specific-detection-of-asian-and-african-lineage-zika-viruses
#18
Nunya Chotiwan, Connie D Brewster, Tereza Magalhaes, James Weger-Lucarelli, Nisha K Duggal, Claudia Rückert, Chilinh Nguyen, Selene M Garcia Luna, Joseph R Fauver, Barb Andre, Meg Gray, William C Black, Rebekah C Kading, Gregory D Ebel, Guillermina Kuan, Angel Balmaseda, Thomas Jaenisch, Ernesto T A Marques, Aaron C Brault, Eva Harris, Brian D Foy, Sandra L Quackenbush, Rushika Perera, Joel Rovnak
Understanding the dynamics of Zika virus transmission and formulating rational strategies for its control require precise diagnostic tools that are also appropriate for resource-poor environments. We have developed a rapid and sensitive loop-mediated isothermal amplification (LAMP) assay that distinguishes Zika viruses of Asian and African lineages. The assay does not detect chikungunya virus or flaviviruses such as dengue, yellow fever, or West Nile viruses. The assay conditions allowed direct detection of Zika virus RNA in cultured infected cells; in mosquitoes; in virus-spiked samples of human blood, plasma, saliva, urine, and semen; and in infected patient serum, plasma, and semen samples without the need for RNA isolation or reverse transcription...
May 3, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28465426/a-novel-agonist-of-the-trif-pathway-induces-a-cellular-state-refractory-to-replication-of-zika-chikungunya-and-dengue-viruses
#19
Kara M Pryke, Jinu Abraham, Tina M Sali, Bryan J Gall, Iris Archer, Andrew Liu, Shelly Bambina, Jason Baird, Michael Gough, Marita Chakhtoura, Elias K Haddad, Ilsa T Kirby, Aaron Nilsen, Daniel N Streblow, Alec J Hirsch, Jessica L Smith, Victor R DeFilippis
The ongoing concurrent outbreaks of Zika, Chikungunya, and dengue viruses in Latin America and the Caribbean highlight the need for development of broad-spectrum antiviral treatments. The type I interferon (IFN) system has evolved in vertebrates to generate tissue responses that actively block replication of multiple known and potentially zoonotic viruses. As such, its control and activation through pharmacological agents may represent a novel therapeutic strategy for simultaneously impairing growth of multiple virus types and rendering host populations resistant to virus spread...
May 2, 2017: MBio
https://www.readbyqxmd.com/read/28453962/a-bead-based-immunofluorescence-assay-on-a-microfluidic-dielectrophoresis-platform-for-rapid-dengue-virus-detection
#20
Edwar Iswardy, Tien-Chun Tsai, I-Fang Cheng, Tzu-Chuan Ho, Guey Chuen Perng, Hsien-Chang Chang
The proof of concept of utilizing a microfluidic dielectrophoresis (DEP) chip was conducted to rapidly detect a dengue virus (DENV) in vitro based on the fluorescence immunosensing. The mechanism of detection was that the DEP force was employed to capture the modified beads (mouse anti-flavivirus monoclonal antibody-coated beads) in the microfluidic chip and the DENV modified with fluorescence label, as the detection target, can be then captured on the modified beads by immunoreaction. The fluorescent signal was then obtained through fluorescence microscopy, and then quantified by ImageJ freeware...
September 15, 2017: Biosensors & Bioelectronics
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