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Flavivirus

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1. Co-circulation of Aedes flavivirus, Culex flavivirus, and Quang Binh virus in Shanghai, China (PubMed)

Co-circulation of Aedes flavivirus, Culex flavivirus, and Quang Binh virus in Shanghai, China With increases in global travel and trade, the spread of arboviruses is undoubtedly alarming. Pathogen detection in field-caught mosquitoes can provide the earliest possible warning of transmission. Insect-specific flavivirus (ISFV) has been first detected in 1991 and documented worldwide in the latest ten years. Although infection with ISFVs is apparently limited to insects, an increase (...) by the sequencing of PCR products. Sequences from positive pooled samples were compared with those deposited in GenBank. Thereafter, sequences of representative insect flaviviruses were used for further phylogenetic and molecular evolutionary analyses.Our investigations showed: (1) the presence of Aedes flavivirus (AEFV) in 11/161 pooled samples (nine pools in Songjiang District, one pool in Huangpu District, and one pool in Qingpu District) of Aedes albopictus, (2) the presence of Quang Binh virus (QBV) in 10

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2018 Infectious diseases of poverty

2. A Phase 1, First-in-human, Double-blinded, Randomized, Placebo-controlled Trial of a Zika Virus Purified Inactivated Vaccine (ZPIV) With Alum Adjuvant in Healthy Flavivirus-naive and Flavivirus-Primed Subjects.

A Phase 1, First-in-human, Double-blinded, Randomized, Placebo-controlled Trial of a Zika Virus Purified Inactivated Vaccine (ZPIV) With Alum Adjuvant in Healthy Flavivirus-naive and Flavivirus-Primed Subjects. A Phase 1, First-in-human, Double-blinded, Randomized, Placebo-controlled Trial of a Zika Virus Purified Inactivated Vaccine (ZPIV) With Alum Adjuvant in Healthy Flavivirus-naive and Flavivirus-Primed Subjects. - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record (...) managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. A Phase 1, First-in-human, Double-blinded, Randomized, Placebo-controlled Trial of a Zika Virus Purified Inactivated Vaccine (ZPIV) With Alum Adjuvant in Healthy Flavivirus-naive and Flavivirus-Primed Subjects. The safety and scientific

2016 Clinical Trials

3. Detection of Culex flavivirus and Aedes flavivirus nucleotide sequences in mosquitoes from parks in the city of São Paulo, Brazil. (PubMed)

Detection of Culex flavivirus and Aedes flavivirus nucleotide sequences in mosquitoes from parks in the city of São Paulo, Brazil. The dengue viruses are widespread in Brazil and are a major public health concern. Other flaviviruses also cause diseases in humans, although on a smaller scale. The city of São Paulo is in a highly urbanized area with few green spaces apart from its parks, which are used for recreation and where potential vertebrate hosts and mosquito vectors of pathogenic (...) Flavivirus species can be found. Although this scenario can contribute to the transmission of Flavivirus to humans, little is known about the circulation of members of this genus in these areas. In light of this, the present study sought to identify Flavivirus infection in mosquitoes (Diptera: Culicidae) collected in parks in the city of São Paulo. Seven parks in different sectors of the city were selected. Monthly mosquito collections were carried out in each park from March 2011 to February 2012 using

2016 Acta Tropica

4. A glance at subgenomic flavivirus RNAs and microRNAs in flavivirus infections (PubMed)

A glance at subgenomic flavivirus RNAs and microRNAs in flavivirus infections The family Flaviviridae comprises a wide variety of viruses that are distributed worldwide, some of which are associated with high rates of morbidity and mortality. There are neither vaccines nor antivirals for most flavivirus infections, reinforcing the importance of research on different aspects of the viral life cycle. During infection, cytoplasmic accumulation of RNA fragments mainly originating from the 3' UTRs (...) , which have been designated subgenomic flavivirus RNAs (sfRNAs), has been detected. It has been shown that eukaryotic exoribonucleases are involved in viral sfRNA production. Additionally, viral and human small RNAs (sRNAs) have also been found in flavivirus-infected cells, especially microRNAs (miRNAs). miRNAs were first described in eukaryotic cells and in a mature and functional state present as single-stranded 18-24 nt RNA fragments. Their main function is the repression of translation through

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2016 Virology journal

5. Does adaptation to vertebrate codon usage relate to flavivirus emergence potential? (PubMed)

Does adaptation to vertebrate codon usage relate to flavivirus emergence potential? Codon adaptation index (CAI) is a measure of synonymous codon usage biases given a usage reference. Through mutation, selection, and drift, viruses can optimize their replication efficiency and produce more offspring, which could increase the chance of secondary transmission. To evaluate how higher CAI towards the host has been associated with higher viral titers, we explored temporal trends of several historic (...) and extensively sequenced zoonotic flaviviruses and relationships within the genus itself. To showcase evolutionary and epidemiological relationships associated with silent, adaptive synonymous changes of viruses, we used codon usage tables from human housekeeping and antiviral immune genes, as well as tables from arthropod vectors and vertebrate species involved in the flavivirus maintenance cycle. We argue that temporal trends of CAI changes could lead to a better understanding of zoonotic emergences

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2018 PLoS ONE

6. Screening test for neutralizing antibodies against yellow fever virus, based on a flavivirus pseudotype. (PubMed)

Screening test for neutralizing antibodies against yellow fever virus, based on a flavivirus pseudotype. Given the possibility of yellow fever virus reintroduction in epidemiologically receptive geographic areas, the risk of vaccine supply disruption is a serious issue. New strategies to reduce the doses of injected vaccines should be evaluated very carefully in terms of immunogenicity. The plaque reduction test for the determination of neutralizing antibodies (PRNT) is particularly time (...) never exposed to flavivirus infection or vaccination, and in patients sampled some time after acute Dengue infection. This WN/YF17D test will be particularly useful for large epidemiological studies and for screening for neutralizing antibodies against yellow fever virus.

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2017 PLoS ONE

7. Immunogenicity and Safety of Tetravalent Dengue Vaccine Candidate (TDV) in Flavivirus-Naïve and Dengue-Immune Adults

Immunogenicity and Safety of Tetravalent Dengue Vaccine Candidate (TDV) in Flavivirus-Naïve and Dengue-Immune Adults Immunogenicity and Safety of Tetravalent Dengue Vaccine Candidate (TDV) in Flavivirus-Naïve and Dengue-Immune Adults - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number (...) of saved studies (100). Please remove one or more studies before adding more. Immunogenicity and Safety of Tetravalent Dengue Vaccine Candidate (TDV) in Flavivirus-Naïve and Dengue-Immune Adults The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. of clinical studies and talk to your health care provider before participating. Read our for details

2018 Clinical Trials

8. Phospholipase A2 activity during the replication cycle of the flavivirus West Nile virus (PubMed)

Phospholipase A2 activity during the replication cycle of the flavivirus West Nile virus Positive-sense RNA virus intracellular replication is intimately associated with membrane platforms that are derived from host organelles and comprised of distinct lipid composition. For flaviviruses, such as West Nile virus strain Kunjin virus (WNVKUN) we have observed that these membrane platforms are derived from the endoplasmic reticulum and are rich in (at least) cholesterol. To extend these studies

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2018 PLoS pathogens

9. Exosomes serve as novel modes of tick-borne flavivirus transmission from arthropod to human cells and facilitates dissemination of viral RNA and proteins to the vertebrate neuronal cells (PubMed)

Exosomes serve as novel modes of tick-borne flavivirus transmission from arthropod to human cells and facilitates dissemination of viral RNA and proteins to the vertebrate neuronal cells Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate (...) transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes with the size range of 30 to 200 nm in diameter. Both positive and negative strands of LGTV RNA

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2018 PLoS pathogens

10. Flavivirus internalization is regulated by a size-dependent endocytic pathway (PubMed)

Flavivirus internalization is regulated by a size-dependent endocytic pathway Flaviviruses enter host cells through the process of clathrin-mediated endocytosis, and the spectrum of host factors required for this process are incompletely understood. Here we found that lymphocyte antigen 6 locus E (LY6E) promotes the internalization of multiple flaviviruses, including West Nile virus, Zika virus, and dengue virus. Perhaps surprisingly, LY6E is dispensable for the internalization (...) infection and bead internalization, and we found that tubule formation was dependent on RNASEK, which is also required for flavivirus internalization, but not transferrin uptake. Indeed, we found that RNASEK is also required for the internalization of transferrin-coated beads, suggesting it functions upstream of LY6E. These LY6E tubules resembled microtubules, and we found that microtubule assembly was required for their formation and flavivirus uptake. Since microtubule end-binding proteins link

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2018 Proceedings of the National Academy of Sciences of the United States of America

11. Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases (PubMed)

Structural and Functional Basis of the Fidelity of Nucleotide Selection by Flavivirus RNA-Dependent RNA Polymerases Viral RNA-dependent RNA polymerases (RdRps) play a central role not only in viral replication, but also in the genetic evolution of viral RNAs. After binding to an RNA template and selecting 5'-triphosphate ribonucleosides, viral RdRps synthesize an RNA copy according to Watson-Crick base-pairing rules. The copy process sometimes deviates from both the base-pairing rules specified (...) and mechanistic basis of the fidelity of nucleotide selection and RNA synthesis by Flavivirus RdRps.

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2018 Viruses

12. Breeding consequences of flavivirus infection in the collared flycatcher (PubMed)

Breeding consequences of flavivirus infection in the collared flycatcher The breeding consequences of virus infections have rarely been studied in avian natural breeding populations. In this paper we investigated the links between humoral immunity following a natural flavivirus infection and reproduction in a wild bird population of collared flycatcher (Ficedula albicollis). We analyzed plasma from 744 birds for antibodies and correlated these results to a number of reproductive (...) components.Nearly one third (27.8%) of the sampled collared flycatchers were found seropositive for flavivirus. Males had significantly more frequently flavivirus antibodies (32.3%) than females (25.1%). Seropositive females differed significantly from seronegative females in four traits: they had earlier lay date, higher body weight, higher survival rate and were older than seronegative females. The females did not differ in clutch size, number of fledged young or number of recruited young. Seropositive males

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2018 BMC evolutionary biology

13. Toll-Like Receptors and RIG-I-Like Receptors Play Important Roles in Resisting Flavivirus (PubMed)

Toll-Like Receptors and RIG-I-Like Receptors Play Important Roles in Resisting Flavivirus Flaviviridae family is a class of single-stranded RNA virus, which is fatal to human and animals and mainly prevalent in subtropic and tropic countries. Even though people and animals are barraged with flavivirus infection every year, we have not invented either vaccines or antiviral for most flavivirus infections yet. Innate immunity is the first line of defense in resisting pathogen invasion, serving (...) an important role in a resisting virus. Toll-like receptors (TLRs) and retinoic acid-inducible gene I- (RIG-I-) like receptors (RLRs) are crucial pattern recognition receptors (PRRs) that play essential roles in recognizing and clearing pathogens, including resisting flavivirus. In the present review, we provide a significant reference for further research on the function of innate immunity in resisting flavivirus.

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2018 Journal of immunology research

14. Incorporation of IgG Depletion in a Neutralization Assay Facilitates Differential Diagnosis of Zika and Dengue in Secondary Flavivirus Infection Cases (PubMed)

Incorporation of IgG Depletion in a Neutralization Assay Facilitates Differential Diagnosis of Zika and Dengue in Secondary Flavivirus Infection Cases Zika virus (ZIKV) has emerged as a major global public health concern due to its link as a causative agent of human birth defects. Laboratory diagnosis of suspected ZIKV infections by serological testing of specimens collected a week or more after symptom onset primarily relies on detection of anti-ZIKV-specific IgM antibodies by enzyme-linked (...) of PRNT for better confirmation and differential diagnosis of flavivirus infections.Copyright © 2018 American Society for Microbiology.

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2018 Journal of clinical microbiology

15. Culex flavivirus infection in a Culex pipiens mosquito colony and its effects on vector competence for Rift Valley fever phlebovirus (PubMed)

Culex flavivirus infection in a Culex pipiens mosquito colony and its effects on vector competence for Rift Valley fever phlebovirus Rift Valley fever is a mosquito-borne zoonotic disease that affects domestic ruminants and humans. Culex flavivirus is an insect-specific flavivirus that naturally exists in field mosquito populations. The influence of Culex flavivirus on Rift Valley fever phlebovirus (RVFV) vector competence of Culex pipiens has not been investigated.Culex flavivirus infection (...) in a Cx. pipiens colony was studied by Culex flavivirus oral feeding and intrathoracical inoculation. Similarly, vector competence of Cx. pipiens infected with Culex flavivirus was evaluated for RVFV. Infection, dissemination, transmission rates and transmission efficiency of Culex flavivirus-infected and non-infected Cx. pipiens artificially fed with RVFV infected blood were assessed.Culex flavivirus was able to infect Cx. pipiens after intrathoracically inoculation in Cx. pipiens mosquitos

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2018 Parasites & vectors

16. Perturbation of Intracellular Cholesterol and Fatty Acid Homeostasis During Flavivirus Infections (PubMed)

Perturbation of Intracellular Cholesterol and Fatty Acid Homeostasis During Flavivirus Infections Cellular lipid homeostasis is maintained through an intricately linked array of anabolic and catabolic pathways. Upon flavivirus infections, these are significantly altered: on the one hand, these viruses can co-opt lipid metabolic pathways to generate ATP to facilitate replication, or to synthesize membrane components to generate replication sites; on the other hand, more recent evidence suggests

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2018 Frontiers in immunology

17. 4-Thiazolidinone coumarin derivatives as two-component NS2B/NS3 DENV flavivirus serine protease inhibitors: synthesis, molecular docking, biological evaluation and structure–activity relationship studies (PubMed)

4-Thiazolidinone coumarin derivatives as two-component NS2B/NS3 DENV flavivirus serine protease inhibitors: synthesis, molecular docking, biological evaluation and structure–activity relationship studies A series of novel 4-thiazolidinone inhibitors SKYa-SKYg, containing coumarin as a core structure were synthesized via facile and efficient method. The structures of the synthesized compounds were established by extensive spectroscopic studies (FT IR, 1D NMR, 2D NMR, LC-MS) and elemental (...) the highest inhibition against all the bacterial strains ranging from 41 to 165 μg/mL, as compared to the standards, streptomycin, kanamycin and vancomycin. Moreover, derivative SKYa was found to be the strongest against M. tuberculosis (83 μg/mL). Additionally, the anti-dengue potential of the coumarin hybrids as two-component NS2B/NS3 DENV flavivirus serine protease inhibitors was calculated using computational molecular docking approach, with reference to the standards 4-hydroxypanduratin, panduratin

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2018 Chemistry Central journal

18. Wolbachia enhances insect‐specific flavivirus infection in Aedes aegypti mosquitoes (PubMed)

Wolbachia enhances insect‐specific flavivirus infection in Aedes aegypti mosquitoes Mosquitoes transmit a diverse group of human flaviviruses including West Nile, dengue, yellow fever, and Zika viruses. Mosquitoes are also naturally infected with insect-specific flaviviruses (ISFs), a subgroup of the family not capable of infecting vertebrates. Although ISFs are not medically important, they are capable of altering the mosquito's susceptibility to flaviviruses and may alter host fitness (...) zones. All field mosquitoes were screened for the presence of ISFs using general degenerate flavivirus primers and their PCR amplicons sequenced. ISFs were found to be common and widely distributed in Ae. aegypti populations. Field mosquitoes consistently had higher ISF infection rates and viral loads compared to laboratory colony material indicating that environmental conditions may modulate ISF infection in Ae. aegypti. Surprisingly, higher ISF infection rates and loads were found in Wolbachia

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2018 Ecology and evolution

19. Detection of Specific ZIKV IgM in Travelers Using a Multiplexed Flavivirus Microsphere Immunoassay (PubMed)

Detection of Specific ZIKV IgM in Travelers Using a Multiplexed Flavivirus Microsphere Immunoassay Zika virus (ZIKV) has spread widely in the Pacific and recently throughout the Americas. Unless detected by RT-PCR, confirming an acute ZIKV infection can be challenging. We developed and validated a multiplexed flavivirus immunoglobulin M (IgM) microsphere immunoassay (flaviMIA) which can differentiate ZIKV-specific IgM from that due to other flavivirus infections in humans. The flaviMIA bound 12 (...) inactivated flavivirus antigens, including those from ZIKV and yellow fever virus (YFV), to distinct anti-flavivirus antibody coupled beads. These beads were used to interrogate sera from patients with suspected ZIKV infection following travel to relevant countries. FlaviMIA results were validated by comparison to the ZIKV plaque reduction neutralization test (PRNT). The results highlight the complexity of serological ZIKV diagnosis, particularly in patients previously exposed to or vaccinated against

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2018 Viruses

20. Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells (PubMed)

Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells How previous immunity influences immune memory recall and protection against related flaviviruses is largely unknown, yet encounter with multiple flaviviruses in a lifetime is increasingly likely. Using sequential challenges with dengue virus (DENV), yellow fever virus (YFV), and Japanese encephalitis virus (JEV), we induced cross-reactive cellular and humoral immunity among flaviviruses (...) from differing serocomplexes. Antibodies against JEV enhanced DENV replication; however, JEV immunity was protective in vivo during secondary DENV1 infection, promoting rapid gains in antibody avidity. Mechanistically, JEV immunity activated dendritic cells and effector memory T cells, which developed a T follicular helper cell phenotype in draining lymph nodes upon secondary DENV1 infection. We identified cross-reactive epitopes that promote recall from a pool of flavivirus serocomplex cross

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2018 Science advances

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