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vector competence of american mosquitoes for three strains of zika virus.in 2015, zika virus (zikv; flaviviridae; flavivirus) emerged in the americas, causing millions of infections in dozens of countries. the rapid spread of the virus and the association with disease outcomes such as guillain-barré syndrome and microcephaly make understanding transmission dynamics essential. currently, there are no reports of vector competence (vc) of american mosquitoes for zikv isolates from the americas. further, it is not clear whether zikv strains from other genetic lineages ca ...201627783679
zika virus (zikv). 201627994533
zika virus infection during the period of maximal brain growth causes microcephaly and corticospinal neuron apoptosis in wild type mice.zika virus (zikv) infection in pregnant women has been established as a cause of microcephaly in newborns. here we test the hypothesis that neurodevelopmental stages when the brain is undergoing rapid growth are particularly vulnerable to the effects of zikv infection. we injected zikv intracranially into wild type c57bl/6 mice at two different time points: early postnatal development, when the brain is growing at its maximal rate, and at weaning, when the brain has largely reached adult size. b ...201627713505
zika virus on a spreading spree: what we now know that was unknown in the 1950's.zika virus (zikv) is a mosquito-borne flavivirus that is transmitted through the bite of aedes spp mosquitoes and less predominantly, through sexual intercourse. prior to 2007, zikv was associated with only sporadic human infections with minimal or no clinical manifestations. recently the virus has caused disease outbreaks from the pacific islands, the americas, and off the coast of west africa with approximately 1.62 million people suspected to be infected in more than 60 countries around the g ...201627716242
full genome sequence and sfrna interferon antagonist activity of zika virus from recife, brazil.the outbreak of zika virus (zikv) in the americas has transformed a previously obscure mosquito-transmitted arbovirus of the flaviviridae family into a major public health concern. little is currently known about the evolution and biology of zikv and the factors that contribute to the associated pathogenesis. determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative proces ...201627706161
available evidence of association between zika virus and microcephaly.to clarify the possible association between the zika virus (zikv) and microcephaly and understand where we are in terms of research and the debate on the causation between mild maternal clinical features and severe fetal microcephaly.027647195
evaluation of realstar reverse transcription-polymerase chain reaction kits for filovirus detection in the laboratory and field.diagnosis of ebola virus (ebov) disease (evd) requires laboratory testing.201627549586
biological control of mosquito vectors: past, present, and future.mosquitoes represent the major arthropod vectors of human disease worldwide transmitting malaria, lymphatic filariasis, and arboviruses such as dengue virus and zika virus. unfortunately, no treatment (in the form of vaccines or drugs) is available for most of these diseases andvectorcontrolisstillthemainformofprevention. thelimitationsoftraditionalinsecticide-based strategies, particularly the development of insecticide resistance, have resulted in significant efforts to develop alternative eco-f ...201627706105
zika virus causing encephalomyelitis associated with immunoactivation.brazil has experienced a zika virus (zikv) outbreak with increased incidence of congenital malformations and neurological manifestations. we describe a case of a 26-year-old brazilian caucasian man infected with zikv and diagnosed with encephalomyelitis. brain and spinal cord images showed hyperintense lesions on t2 and fluid-attenuated inversion recovery (flair), and levels of proinflammatory cytokines in the cerebrospinal fluid showed a remarkable increase of interleukin (il)-6 and il-8. the o ...201628053996
viral rna switch mediates the dynamic control of flavivirus replicase recruitment by genome cyclization.viral replicase recruitment and long-range rna interactions are essential for rna virus replication, yet the mechanism of their interplay remains elusive. flaviviruses include numerous important human pathogens, e.g., dengue virus (denv) and zika virus (zikv). here, we revealed a highly conserved, conformation-tunable cis-acting element named 5'-uar-flanking stem (ufs) in the flavivirus genomic 5' terminus. we demonstrated that the ufs was critical for efficient ns5 recruitment and viral rna syn ...201627692070
zika virus and guillain-barre syndrome: is there sufficient evidence for causality?worldwide concern over zika virus causing guillain-barre syndrome (gbs) soared after recent reports that zika-related weakness was due to gbs. a global strategic response plan was initiated with recommendations for at-risk countries to prepare for gbs. this plan has major economic implications, as nations with limited resources struggle to implement costly immunotherapy. since confirmation of causality is prerequisite to providing specific management recommendations, it is prudent to review data ...201627746763
management of infection by the zika virus.a panel of national experts was convened by the brazilian infectious diseases society in order to organize the national recommendations for the management of zika virus infection. the focus of this document is the diagnosis, both clinical and laboratorial, and appropriate treatment of the diverse manifestations of this infection, ranging from acute mild disease to guillain-barré syndrome and also microcephaly and congenital malformations.201627686610
the golgi associated eri3 is a flavivirus host factor.dengue virus (denv) is a mosquito-borne flavivirus classified into four serotypes (denv-1-4) that causes dengue fever (df), dengue hemorrhagic fever (dhf) or dengue shock syndrome (dss). an estimated 390 million people are at risk for infection with denv and there are no effective vaccines or therapeutics. we utilized rna chromatography coupled with quantitative mass spectrometry (qms) to identify host rna binding proteins (rbps) that interact with denv-2 rna. we identified eri3 (also prnpip and ...201627682269
rescue of the 1947 zika virus prototype strain with a cytomegalovirus promoter-driven cdna clone.the recent zika virus (zikv) outbreak has been linked to severe pathogenesis. here, we report the construction of a plasmid carrying a cytomegalovirus (cmv) promoter-expressed prototype 1947 uganda mr766 zikv cdna that can initiate infection following direct plasmid dna transfection of mammalian cells. incorporation of a synthetic intron in the nonstructural protein 1 (ns1) region of the zikv polyprotein reduced viral cdna-associated toxicity in bacteria. high levels of infectious virus were pro ...201627704051
characterization of a 2016 clinical isolate of zika virus in non-human primates.animal models are critical to understand disease and to develop countermeasures for the ongoing epidemics of zika virus (zikv). here we report a non-human primate model using a 2016 contemporary clinical isolate of zikv. upon subcutaneous inoculation, rhesus macaques developed fever and viremia, with robust excretion of zikv rna in urine, saliva, and lacrimal fluid. necropsy of two infected animals revealed that systematic infections involving central nervous system and visceral organs were esta ...201627693104
flavidb: a data mining system for knowledge discovery in flaviviruses with direct applications in immunology and vaccinology.the flavivirus genus is unusually large, comprising more than 70 species, of which more than half are known human pathogens. it includes a set of clinically relevant infectious agents such as dengue, west nile, yellow fever, and japanese encephalitis viruses. although these pathogens have been studied extensively, safe and efficient vaccines lack for the majority of the flaviviruses.025544857
dna microarray platform for detection and surveillance of viruses transmitted by small mammals and arthropods.viruses transmitted by small mammals and arthropods serve as global threats to humans. most emergent and re-emergent viral agents are transmitted by these groups; therefore, the development of high-throughput screening methods for the detection and surveillance of such viruses is of great interest. in this study, we describe a dna microarray platform that can be used for screening all viruses transmitted by small mammals and arthropods (smaviruschip) with nucleotide sequences that have been depo ...201627654806
characterization of a zika virus isolate from colombia.zika virus (flavivirus genus) is the first mosquito-borne virus known to cause high rates of microcephaly and abortion in humans. typically, zika virus causes a self-limiting, systemic illness; however, the current outbreak of zika virus in the americas has been associated with increased rates of fetal malformations and guillain-barré syndrome. very few zika virus isolates have been described in the literature, and live viruses are needed to perform studies of pathogenesis and to develop vaccine ...201627654889
zika virus replicons for drug discovery.the current epidemic of zika virus (zikv) has underscored the urgency to establish experimental systems for studying viral replication and pathogenesis, and countermeasure development. here we report two zikv replicon systems: a luciferase replicon that can differentiate between viral translation and rna synthesis; and a stable luciferase replicon carrying cell line that can be used to screen and characterize inhibitors of viral replication. the transient replicon was used to evaluate the effect ...201627658737
archival collections are important in the study of the biology, diversity, and evolution of arboviruses.historically, classifications of arboviruses were based on serological techniques. hence, collections of arbovirus isolates have been central to this process by providing the antigenic reagents for these methods. however, with increasing concern about biosafety and security, the introduction of molecular biology techniques has led to greater emphasis on the storage of nucleic acid sequence data over the maintenance of archival material. in this commentary, we provide examples of where archival c ...201627688704
detection of invasive mosquito vectors using environmental dna (edna) from water samples.repeated introductions and spread of invasive mosquito species (ims) have been recorded on a large scale these last decades worldwide. in this context, members of the mosquito genus aedes can present serious risks to public health as they have or may develop vector competence for various viral diseases. while the tiger mosquito (aedes albopictus) is a well-known vector for e.g. dengue and chikungunya viruses, the asian bush mosquito (ae. j. japonicus) and ae. koreicus have shown vector competenc ...201627626642
computational analysis of perturbations in the post-fusion dengue virus envelope protein highlights known epitopes and conserved residues in the zika virus.the dramatic transformation of the zika virus (zikv) from a relatively unknown virus to a pathogen generating global-wide panic has exposed the dearth of detailed knowledge about this virus. decades of research in the related dengue virus (denv), finally culminating in a vaccine registered for use in endemic regions (cyd-tdv) in three countries, provides key insights in developing strategies for tackling zikv, which has caused global panic to microcephaly and guillain-barre syndrome. dengue viru ...201627540468
new paradigms for virus detection, surveillance and control of zika virus vectors in the settings of southeast asia.zika virus (zikv) has now become a global public health concern. the vectors for zikv are aedes aegypti and a. albopictus. both these mosquitoes are predominant in southeast asia and are also responsible for the spread of other arboviral diseases like dengue virus and chikungunya virus. the incidence of dengue has been increasing over the years and this is of concern to public health workers. simple laboratory tools for the detection of zikv is also lacking. in the absence of drugs and vaccine f ...201627679623
structures of ns5 methyltransferase from zika virus.the zika virus (zikv) poses a major public health emergency. to aid in the development of antivirals, we present two high-resolution crystal structures of the zikv ns5 methyltransferase: one bound to s-adenosylmethionine (sam) and the other bound to sam and 7-methyl guanosine diphosphate (7-megpp). we identify features of zikv ns5 methyltransferase that lend to structure-based antiviral drug discovery. specifically, sam analogs with functionalities on the cβ atom of the methionine portion of the ...201627633330
culex pipiens quinquefasciatus: a potential vector to transmit zika virus.zika virus (zikv) has become a threat to global health since the outbreak in brazil in 2015. although zikv is generally considered an aedes-transmitted pathogen, new evidence has shown that parts of the virus closely resemble culex-transmitted viruses. therefore, it is important to evaluate the competence of culex species for zikv to understand their potential as vectors. in this study, female culex pipiens quinquefasciatus were orally exposed to zikv. mosquito midguts, salivary glands and ovari ...201627599470
nonstructural proteins are preferential positive selection targets in zika virus and related flaviviruses.the flavivirus genus comprises several human pathogens such as dengue virus (denv), japanese encephalitis virus (jev), and zika virus (zikv). although zikv usually causes mild symptoms, growing evidence is linking it to congenital birth defects and to increased risk of guillain-barré syndrome. zikv encodes a polyprotein that is processed to produce three structural and seven nonstructural (ns) proteins. we investigated the evolution of the viral polyprotein in zikv and in related flaviviruses (d ...201627588756
molecular signatures associated with zikv exposure in human cortical neural progenitors.zika virus (zikv) infection causes microcephaly and has been linked to other brain abnormalities. how zikv impairs brain development and function is unclear. here we systematically profiled transcriptomes of human neural progenitor cells exposed to asian zikv(c), african zikv(m), and dengue virus (denv). in contrast to the robust global transcriptome changes induced by denv, zikv has a more selective and larger impact on expression of genes involved in dna replication and repair. while overall e ...201627580721
adenosine analog nitd008 is a potent inhibitor of zika virus.the ongoing zika virus (zikv) outbreaks have raised global concerns due to its unexpected clinical manifestations. antiviral development is of high priority in response to the zikv emergency. in this study, we report that an adenosine analog nitd008 has potent in vitro and in vivo antiviral activity against zikv. the compound can effectively inhibit the historical and contemporary zikv strains in cultures as well as significantly reduce viremia and prevent mortality in a129 mice. our results hav ...201627747251
the dengue virus ns5 protein intrudes in the cellular spliceosome and modulates splicing.dengue virus ns5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral rna replication and counteracting host antiviral responses. here, we demonstrate a novel function of ns5 in the nucleus where it interferes with cellular splicing. using global proteomic analysis of infected cells together with functional studies, we found that ns5 binds spliceosome complexes and modulates endogenous splicing as well as minigene-derived alternative splicing patterns. in particula ...201627575636
zika fetal neuropathogenesis: etiology of a viral syndrome.the ongoing zika virus epidemic in the americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (guillain-barré syndrome) has brought attention to this neglected pathogen. while initial case studies generated significant interest in the zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of zika viral infection and associated pathophysiology are only now starting to be published. ...201627560129
antiviral activity of a novel compound cw-33 against japanese encephalitis virus through inhibiting intracellular calcium overload.japanese encephalitis virus (jev), a mosquito-borne flavivirus, has five genotypes (i, ii, iii, iv, and v). jev genotype i circulates widely in some asian countries. however, current jev vaccines based on genotype iii strains show low neutralizing capacities against genotype i variants. in addition, je has no specific treatment, except a few supportive treatments. compound cw-33, an intermediate synthesized derivative of furoquinolines, was investigated for its antiviral activities against jev i ...201627563890
differential cell line susceptibility to the emerging zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs.zika virus (zikv) is unique among human-pathogenic flaviviruses by its association with congenital anomalies and trans-placental and sexual human-to-human transmission. although the pathogenesis of zikv-associated neurological complications has been reported in recent studies, key questions on the pathogenesis of the other clinical manifestations, non-vector-borne transmission and potential animal reservoirs of zikv remain unanswered. we systematically characterized the differential cell line su ...201627553173
an ultrasensitive electrogenerated chemiluminescence-based immunoassay for specific detection of zika virus.zika virus (zikv) is a globally emerging mosquito-transmitted flavivirus that can cause severe fetal abnormalities, including microcephaly. as such, highly sensitive, specific, and cost-effective diagnostic methods are urgently needed. here, we report a novel electrogenerated chemiluminescence (ecl)-based immunoassay for ultrasensitive and specific detection of zikv in human biological fluids. we loaded polystyrene beads (psb) with a large number of ecl labels and conjugated them with anti-zikv ...201627554037
first case of laboratory-confirmed zika virus infection imported into china. 027503033
modeling mosquito-borne disease spread in u.s. urbanized areas: the case of dengue in miami.expansion of mosquito-borne pathogens into more temperate regions of the world necessitates tools such as mathematical models for understanding the factors that contribute to the introduction and emergence of a disease in populations naïve to the disease. often, these models are not developed and analyzed until after a pathogen is detected in a population. in this study, we develop a spatially explicit stochastic model parameterized with publicly available u.s. census data for studying the poten ...201627532496
invasion dynamics of teratogenic infections in light of rubella control: implications for zika virus.the greatest burden for a subset of pathogens is associated with infection during pregnancy. evidence for teratogenic effects of zika virus have highlighted the importance of understanding the epidemiology of such pathogens. rubella is perhaps the most classic example, and there is much to be learned from the long history of modelling associated with this virus.201627617170
zika virus genomic rna possesses conserved g-quadruplexes characteristic of the flaviviridae family.zika virus has emerged as a global concern because neither a vaccine nor antiviral compounds targeting it exist. a structure for the positive-sense rna genome has not been established, leading us to look for potential g-quadruplex sequences (pqs) in the genome. the analysis identified >60 pqss in the zika genome. to minimize the pqs population, conserved sequences in the flaviviridae family were found by sequence alignment, identifying seven pqss in the prm, e, ns1, ns3, and ns5 genes. next, ali ...201627737553
arboviruses: molecular biology, evolution and control. nikos vasilakis and duane j. gubler. 027489330
the global threat of zika virus to pregnancy: epidemiology, clinical perspectives, mechanisms, and impact.zika virus (zikv) is a mosquito-borne flavivirus that has newly emerged as a significant global threat, especially to pregnancy. recent major outbreaks in the pacific and in central and south america have been associated with an increased incidence of microcephaly and other abnormalities of the central nervous system in neonates. the causal link between zikv infection during pregnancy and microcephaly is now strongly supported. over 2 billion people live in regions conducive to zikv transmission ...201627487767
background review for diagnostic test development for zika virus infection.to review the state of knowledge about diagnostic testing for zika virus infection and identify areas of research needed to address the current gaps in knowledge.027516635
limited effects of type i interferons on kyasanur forest disease virus in cell culture.the tick-borne flavivirus, kyasanur forest disease virus (kfdv) causes seasonal infections and periodic outbreaks in south-west india. the current vaccine offers poor protection with reported issues of coverage and immunogenicity. since there are no approved prophylactic therapeutics for kfdv, type i ifn-α/β subtypes were assessed for antiviral potency against kfdv in cell culture.201627479197
broadly neutralizing activity of zika virus-immune sera identifies a single viral serotype.recent epidemics of zika virus (zikv) have been associated with congenital malformation during pregnancy and guillain-barré syndrome. there are two zikv lineages (african and asian) that share >95% amino acid identity. little is known regarding the ability of neutralizing antibodies elicited against one lineage to protect against the other. we investigated the breadth of the neutralizing antibody response following zikv infection by measuring the sensitivity of six zikv strains to neutralization ...201627481466
flavivirus ns1: a multifaceted enigmatic viral protein.flaviviruses are emerging arthropod-borne viruses representing an immense global health problem. the prominent viruses of this group include dengue virus, yellow fever virus, japanese encephalitis virus, west nile virus tick borne encephalitis virus and zika virus. these are endemic in many parts of the world. they are responsible for the illness ranging from mild flu like symptoms to severe hemorrhagic, neurologic and cognitive manifestations leading to death. ns1 is a highly conserved non-stru ...201627473856
the use of mosquito repellents at three sites in india with declining malaria transmission: surveys in the community and clinic.repellents such as coils, vaporizers, mats and creams can be used to reduce the risk of malaria and other infectious diseases. although evidence for their effectiveness is limited, they are advertised as providing an additional approach to mosquito control in combination with other strategies, e.g. insecticide-treated nets. we examined the use of repellents in india in an urban setting in chennai (mainly plasmodium vivax malaria), a peri-urban setting in nadiad (both p. vivax and p. falciparum m ...201627465199
dengue virus envelope dimer epitope monoclonal antibodies isolated from dengue patients are protective against zika virus.zika virus (zikv) is a mosquito-borne flavivirus responsible for thousands of cases of severe fetal malformations and neurological disease since its introduction to brazil in 2013. antibodies to flaviviruses can be protective, resulting in lifelong immunity to reinfection by homologous virus. however, cross-reactive antibodies can complicate flavivirus diagnostics and promote more severe disease, as noted after serial dengue virus (denv) infections. the endemic circulation of denv in south ameri ...201627435464
structural basis of zika virus helicase in recognizing its substrates.the recent explosive outbreak of zika virus (zikv) infection has been reported in south and central america and the caribbean. neonatal microcephaly associated with zikv infection has already caused a public health emergency of international concern. no specific vaccines or drugs are currently available to treat zikv infection. the zikv helicase, which plays a pivotal role in viral rna replication, is an attractive target for therapy. we determined the crystal structures of zikv helicase-atp-mn( ...201627430951
comparative analysis between flaviviruses reveals specific neural stem cell tropism for zika virus in the mouse developing neocortex.the recent zika outbreak in south america and french polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. other members of the flavivirus genus, including west nile virus (wnv), can cause encephalitis but were not demonstrated to cause microcephaly. it remains unclear whether zika virus (zikv) and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. ...201627453325
larval application of sodium channel homologous dsrna restores pyrethroid insecticide susceptibility in a resistant adult mosquito population.mosquitoes host and pass on to humans a variety of disease-causing pathogens such as infectious viruses and other parasitic microorganisms. the emergence and spread of insecticide resistance is threatening the effectiveness of current control measures for common mosquito vector borne diseases, such as malaria, dengue and zika. therefore, the emerging resistance to the widely used pyrethroid insecticides is an alarming problem for public health. herein we demonstrated the use of rna interference ...201627416771
structure of the ns3 helicase from zika virus.zika virus has emerged as a pathogen of major health concern. here, we present a high-resolution (1.62-å) crystal structure of the rna helicase from the french polynesia strain. the structure is similar to that of the rna helicase from dengue virus, with variability in the conformations of loops typically involved in binding atp and rna. we identify druggable 'hotspots' that are well suited for in silico and/or fragment-based high-throughput drug discovery.201627399257
zika virus as an emerging global pathogen: neurological complications of zika virus.zika virus (zikv) is an emerging arthropod-borne virus (arbovirus) in the genus flavivirus that has caused a widespread outbreak of febrile illness, is associated with neurological disease, and has spread across the pacific to the americas in a short period.027183312
zika virus: epidemiology, current phobia and preparedness for upcoming mass gatherings, with examples from world olympics and pilgrimage.to describe zika virus (zikv) epidemiology, current phobia, and the required preparedness for its prevention during the upcoming mass gathering (mg) events.027648063
a literature review of zika virus.zika virus is a mosquitoborne flavivirus that is the focus of an ongoing pandemic and public health emergency. previously limited to sporadic cases in africa and asia, the emergence of zika virus in brazil in 2015 heralded rapid spread throughout the americas. although most zika virus infections are characterized by subclinical or mild influenza-like illness, severe manifestations have been described, including guillain-barre syndrome in adults and microcephaly in babies born to infected mothers ...201627070380
single-reaction multiplex reverse transcription pcr for detection of zika, chikungunya, and dengue viruses.clinical manifestations of zika virus, chikungunya virus, and dengue virus infections can be similar. to improve virus detection, streamline molecular workflow, and decrease test costs, we developed and evaluated a multiplex real-time reverse transcription pcr for these viruses.201627184629
dengue virus genome uncoating requires ubiquitination.the process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, zika, and west nile viruses. currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. here, we examined for the first time molecular aspect ...201627353759
human antibody responses after dengue virus infection are highly cross-reactive to zika virus.zika virus (zikv) is an emerging mosquito-borne flavivirus of significant public health concern. zikv shares a high degree of sequence and structural homology compared with other flaviviruses, including dengue virus (denv), resulting in immunological cross-reactivity. improving our current understanding of the extent and characteristics of this immunological cross-reactivity is important, as zikv is presently circulating in areas that are highly endemic for dengue. to assess the magnitude and fu ...201627354515
human t cell responses to japanese encephalitis virus in health and disease.japanese encephalitis (je) virus (jev) is an important cause of encephalitis in children of south and southeast asia. however, the majority of individuals exposed to jev only develop mild symptoms associated with long-lasting adaptive immunity. the related flavivirus dengue virus (denv) cocirculates in many jev-endemic areas, and clinical data suggest cross-protection between denv and jev. to address the role of t cell responses in protection against jev, we conducted the first full-breadth anal ...201627242166
neuroprotection mediated by inhibition of calpain during acute viral encephalitis.neurologic complications associated with viral encephalitis, including seizures and cognitive impairment, are a global health issue, especially in children. we previously showed that hippocampal injury during acute picornavirus infection in mice is associated with calpain activation and is the result of neuronal death triggered by brain-infiltrating inflammatory monocytes. we therefore hypothesized that treatment with a calpain inhibitor would protect neurons from immune-mediated bystander injur ...201627345730
il-33 signaling is essential to attenuate viral-induced encephalitis development by downregulating inos expression in the central nervous system.viral encephalitis is a common cause of lethal infections in humans, and several different viruses are documented to be responsible. rocio virus is a flavivirus that causes a severe lethal encephalitis syndrome in humans and also mice, providing an interesting model to study the cns compartmentalized immune response. interleukin 33 (il-33), a member of the il-1 family, is an immunomodulatory cytokine that is highly expressed in the cns. however, the role of il-33 on viral encephalitis remains un ...201627334012
flavivirus ns1 protein in infected host sera enhances viral acquisition by mosquitoes.the arbovirus life cycle involves viral transfer between a vertebrate host and an arthropod vector, and acquisition of virus from an infected mammalian host by a vector is an essential step in this process. here, we report that flavivirus nonstructural protein-1 (ns1), which is abundantly secreted into the serum of an infected host, plays a critical role in flavivirus acquisition by mosquitoes. the presence of dengue virus (denv) and japanese encephalitis virus ns1s in the blood of infected inte ...201627562253
prevention and control of zika as a mosquito-borne and sexually transmitted disease: a mathematical modeling analysis.the ongoing zika virus (zikv) epidemic in the americas poses a major global public health emergency. while zikv is transmitted from human to human by bites of aedes mosquitoes, recent evidence indicates that zikv can also be transmitted via sexual contact with cases of sexually transmitted zikv reported in argentina, canada, chile, france, italy, new zealand, peru, portugal, and the usa. yet, the role of sexual transmission on the spread and control of zikv infection is not well-understood. we i ...201627312324
detection of chikungunya virus in saliva and urine.saliva and urine have been used for arthropod-borne viruses molecular detection but not yet for chikungunya virus (chikv). we investigated the use of saliva and urine for molecular detection of chikv during the french polynesian outbreak.201627306056
virus variation resource - improved response to emergent viral outbreaks.the virus variation resource is a value-added viral sequence data resource hosted by the national center for biotechnology information. the resource is located at http://www.ncbi.nlm.nih.gov/genome/viruses/variation/ and includes modules for seven viral groups: influenza virus, dengue virus, west nile virus, ebolavirus, mers coronavirus, rotavirus a and zika virus each module is supported by pipelines that scan newly released genbank records, annotate genes and proteins and parse sample descript ...201627899678
molecular mechanism of divalent-metal-induced activation of ns3 helicase and insights into zika virus inhibitor design.zika virus has attracted increasing attention because of its potential for causing human neural disorders, including microcephaly in infants and guillain-barré syndrome. its ns3 helicase domain plays critical roles in ntp-dependent rna unwinding and translocation during viral replication. our structural analysis revealed a pre-activation state of ns3 helicase in complex with gtpγs, in which the triphosphate adopts a compact conformation in the absence of any divalent metal ions. in contrast, in ...201627915293
detection of chikungunya virus circulation using sugar-baited traps during a major outbreak in french guiana. 201627606960
mayaro virus and dengue virus 1 and 4 natural infection in culicids from cuiabá, state of mato grosso, brazil.this study aimed to verify the diversity of culicidae species and their frequency of infection with flaviviruses and alphaviruses in cuiabá, state of mato grosso, brazil. mosquitoes were captured with nasci aspirators and hand net in 200 census tracts, identified alive at species level and pooled in one-20 (11,090 mosquitoes, 14 species). female pools (n = 610) were subjected to multiplex seminested-reverse transcription-polymerase chain reaction (rt-pcr) for 11 flavivirus and five alphavirus. p ...026784852
aedes aegypti control strategies in brazil: incorporation of new technologies to overcome the persistence of dengue epidemics.dengue is considered to be the most important mosquito-borne viral disease in the world. the aedes aegypti mosquito, its vector, is highly anthropophilic and is very well adapted to urban environments. although several vaccine candidates are in advanced stages of development no licensed dengue vaccine is yet available. as a result, controlling the spread of dengue still requires that mosquitoes be targeted directly. we review the current methods of dengue vector control focusing on recent techni ...201526463204
enhancement of mosquito trapping efficiency by using pulse width modulated light emitting diodes.in this study, a light-driving bug zapper is presented for well controlling the diseases brought by insects, such as mosquitoes. in order to have the device efficient to trap the insect pests in off-grid areas, pulse width modulated light emitting diodes (pwm-led) combined with a solar power module are proposed and implemented. with specific pwm electric signals to drive the led, it is found that no matter what the ability of catching insects or the consumed power efficiency can be enhanced thus ...201728059148
prolonged detection of zika virus in vaginal secretions and whole blood.infection with zika virus is an emerging public health crisis. we observed prolonged detection of virus rna in vaginal mucosal swab specimens and whole blood for a us traveler with acute zika virus infection who had visited honduras. these findings advance understanding of zika virus infection and provide data for additional testing strategies.201727748649
use of cellular decapping activators by positive-strand rna viruses.positive-strand rna viruses have evolved multiple strategies to not only circumvent the hostile decay machinery but to trick it into being a priceless collaborator supporting viral rna translation and replication. in this review, we describe the versatile interaction of positive-strand rna viruses and the 5'-3' mrna decay machinery with a focus on the viral subversion of decapping activators. this highly conserved viral trickery is exemplified with the plant brome mosaic virus, the animal flock ...201628009841
tlr3 downregulates expression of schizophrenia gene disc1 via myd88 to control neuronal morphology.viral infection during fetal or neonatal stages increases the risk of developing neuropsychiatric disorders such as schizophrenia and autism spectrum disorders. although neurons express several key regulators of innate immunity, the role of neuronal innate immunity in psychiatric disorders is still unclear. using cultured neurons and in vivo mouse brain studies, we show here that toll-like receptor 3 (tlr3) acts through myeloid differentiation primary response gene 88 (myd88) to negatively contr ...201627979975
potential for zika virus to establish a sylvatic transmission cycle in the americas.zika virus (zikv) originated and continues to circulate in a sylvatic transmission cycle between non-human primate hosts and arboreal mosquitoes in tropical africa. recently zikv invaded the americas, where it poses a threat to human health, especially to pregnant women and their infants. here we examine the risk that zikv will establish a sylvatic cycle in the americas, focusing on brazil. we review the natural history of sylvatic zikv and present a mathematical dynamic transmission model to as ...201627977671
risk of zika virus transmission in the euro-mediterranean area and the added value of building preparedness to arboviral threats from a one health perspective.in the alarming context of risk of zika virus (zikv) transmission in the euro-mediterranean area, there is a need to examine whether capacities to detect, diagnose and notify zikv infections in the region are in place and whether ongoing capacity-building initiatives are filling existing gaps.the medilabsecure network, created in 2014, comprises 55 laboratories of virology and medical entomology and 19 public health institutions in 19 countries in the balkans, north-africa, the middle-east and t ...201627914465
assay optimization for molecular detection of zika virus.to examine the diagnostic performance of real-time reverse transcription (rt)-polymerase chain reaction (pcr) assays for zika virus detection.027994281
protective capacity of the human anamnestic antibody response during acute dengue virus infection.half of the world's population is exposed to the risk of dengue virus infection. although a vaccine for dengue virus is now available in a few countries, its reported overall efficacy of about 60% is not ideal. protective immune correlates following natural dengue virus infection remain undefined, which makes it difficult to predict the efficacy of new vaccines. in this study, we address the protective capacity of dengue virus-specific antibodies that are produced by plasmablasts a few days afte ...201627707930
neutralization mechanism of a highly potent antibody against zika virus.the rapid spread of zika virus (zikv), which causes microcephaly and guillain-barré syndrome, signals an urgency to identify therapeutics. recent efforts to rescreen dengue virus human antibodies for zikv cross-neutralization activity showed antibody c10 as one of the most potent. to investigate the ability of the antibody to block fusion, we determined the cryoem structures of the c10-zikv complex at ph levels mimicking the extracellular (ph8.0), early (ph6.5) and late endosomal (ph5.0) environ ...201627882950
zika virus infection in dexamethasone-immunosuppressed mice demonstrating disseminated infection with multi-organ involvement including orchitis effectively treated by recombinant type i interferons.disseminated or fatal zika virus (zikv) infections were reported in immunosuppressed patients. existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons.201627884655
thoughts around the zika virus crisis.as a lot of reviews are available on zika virus (zikv), in this short commentary, we will focus on the recent advances and gaps in knowledge regarding our understanding of zikv infections and on the reaction to the "zikv crisis."027832453
plant virus-insect vector interactions: current and potential future research directions.acquisition and transmission by an insect vector is central to the infection cycle of the majority of plant pathogenic viruses. plant viruses can interact with their insect host in a variety of ways including both non-persistent and circulative transmission; in some cases, the latter involves virus replication in cells of the insect host. replicating viruses can also elicit both innate and specific defense responses in the insect host. a consistent feature is that the interaction of the virus wi ...201627834855
downregulation of aedes aegypti chromodomain helicase dna binding protein 7/kismet by wolbachia and its effect on dengue virus replication.dengue virus (denv) is a mosquito-transmitted virus imposing a significant burden on human health around the world. since current control strategies are not sufficient, there is an urgent need to find alternative methods to control denv transmission. it has been demonstrated that introduction of wolbachia pipientis in aedes aegypti mosquitoes can impede denv transmission with the mechanism(s) not fully understood. recently, a number of studies have found the involvement of chromodomain dna bindi ...201627827425
zika virus epidemic in brazil. i. fatal disease in adults: clinical and laboratorial aspects.zika virus (zikv) was first detected in brazil in may 2015 and the country experienced an explosive epidemic. however, recent studies indicate that the introduction of zikv occurred in late 2013. cases of microcephaly and deaths associated with zikv infection were identified in brazil in november, 2015.201627835759
a mouse model of chronic west nile virus disease.infection with west nile virus (wnv) leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic wnv infection has precluded identification of the immune events contributing to persistent infection. using the collaborative cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent wnv disease, with persistence of viral loads within the brain. compared ...201627806117
transmission bottlenecks and rnai collectively influence tick-borne flavivirus evolution.arthropod-borne rna viruses exist within hosts as heterogeneous populations of viral variants and, as a result, possess great genetic plasticity. understanding the micro-evolutionary forces shaping these viruses can provide insights into how they emerge, adapt, and persist in new and changing ecological niches. while considerable attention has been directed toward studying the population dynamics of mosquito-borne viruses, little is known about tick-borne virus populations. therefore, using a mo ...201628058113
the role of tam family receptors in immune cell function: implications for cancer therapy.the tam receptor protein tyrosine kinases-tyro3, axl, and mer-are essential regulators of immune homeostasis. guided by their cognate ligands growth arrest-specific gene 6 (gas6) and protein s (pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. their central role as negative immune regulators is highlighted by the fact that deregulati ...201627775650
zika virus infection and microcephaly: evidence for a causal link.zika virus (zikv) is a flavivirus related to the dengue, yellow fever and west nile viruses. since the explosive outbreaks of zikv in latin america in 2015, a sudden increase in the number of microcephaly cases has been observed in infants of women who were pregnant when they contracted the virus. the severity of this condition raises grave concerns, and extensive studies on the possible link between zikv infection and microcephaly have been conducted. there is substantial evidence suggesting th ...201627775637
openzika: an ibm world community grid project to accelerate zika virus drug discovery.the zika virus outbreak in the americas has caused global concern. to help accelerate this fight against zika, we launched the openzika project. openzika is an ibm world community grid project that uses distributed computing on millions of computers and android devices to run docking experiments, in order to dock tens of millions of drug-like compounds against crystal structures and homology models of zika proteins (and other related flavivirus targets). this will enable the identification of ne ...201627764115
emergence and spreading potential of zika virus.zika virus (zikv) is an arthropod-borne flavivirus (family flaviviridae) closely related to dengue, yellow fever and west nile viruses. zikv remained neglected, confined to enzootic transmission cycles in africa and asia, until the first significant outbreak was reported in micronesia in 2007. subsequent epidemics of growing incidence occurred in french polynesia and other south pacific islands, and recently, in the americas. the latter and currently ongoing outbreak of unprecedented incidence r ...201627812357
looking backward, looking forward: the long, torturous struggle with mosquitoes.the american anti-mosquito movement grew out of the discovery of the role of mosquitoes in transferring pathogens and public concern about pest and nuisance mosquitoes in the late 1800s. in the 20th century, organized mosquito control in the united states passed through three eras: mechanical, chemical, and integrated mosquito control. mosquito control in the 21st century faces the challenge of emerging pathogens, invasive mosquito species, and balancing concerns about the environment with effec ...201627775554
zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an fda-approved library.background the recent epidemics of zika virus (zikv) implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the guillain-barré syndrome in otherwise healthy patients. recent findings showed that anti-dengue antibodies are capable of amplifying zikv infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. this scenario becomes pot ...201627909576
identifying protective host gene expression signatures within the spleen during west nile virus infection in the collaborative cross model.flaviviruses are hematophagous arthropod-viruses that pose global challenges to human health. like zika virus, west nile virus (wnv) is a flavivirus for which no approved vaccine exists [1]. the role host genetics play in early detection and response to wnv still remains largely unexplained. in order to capture the impact of genetic variation on innate immune responses, we studied gene expression following wnv infection using the collaborative cross (cc). the cc is a mouse genetics resource comp ...201627843766
how did zika virus emerge in the pacific islands and latin america?the unexpected emergence of zika virus (zikv) in the pacific islands and latin america and its association with congenital zika virus syndrome (czvs) (which includes microcephaly) and guillain-barré syndrome (gbs) have stimulated wide-ranging research. high densities of susceptible aedes spp., immunologically naive human populations, global population growth with increased urbanization, and escalation of global transportation of humans and commercial goods carrying vectors and zikv undoubtedly e ...201627729507
the mysterious zika virus: adding to the tropical flavivirus mayhem.until now, known as the demure cousin of dengue virus (denv) inhabiting africa, zika virus (zikv) has reinvented itself to cause explosive epidemics captivating the western hemisphere. the outbreak causing potential for zikv was realized when it made its way from africa to yap island micronesia in 2007, and in french polynesia in 2013. from there, it moved on to brazil in 2015. now zikv has infected people in more than 33 countries in central and south america and the caribbean. moreover the epi ...027763483
long-term health risks in childhood cancer survivors. 027757006
culex pipiens and aedes triseriatus mosquito susceptibility to zika virus. 201627434194
virtual screening for potential inhibitors of ns3 protein of zika virus.zika virus (zikv) is a mosquito borne pathogen, belongs to flaviviridae family having a positive-sense single-stranded rna genome, currently known for causing large epidemics in brazil. its infection can cause microcephaly, a serious birth defect during pregnancy. the recent outbreak of zikv in february 2016 in brazil realized it as a major health risk, demands an enhanced surveillance and a need to develop novel drugs against zikv. amodiaquine, prochlorperazine, quinacrine, and berberine are fe ...201627729840
research contributing to improvements in controlling florida's mosquitoes and mosquito-borne diseases.research on mosquitoes and mosquito-borne diseases has contributed to improvements in providing effective, efficient, and environmentally proper mosquito control. florida has benefitted from several research accomplishments that have increased the state's mosquito control capabilities. research with florida's mosquitoes has resulted in the development of ecologically sound management of mosquito impoundments on florida's east coast. this strategy, called rotational impoundment management (rim), ...201627690112
public health responses to and challenges for the control of dengue transmission in high-income countries: four case studies.dengue has a negative impact in low- and lower middle-income countries, but also affects upper middle- and high-income countries. despite the efforts at controlling this disease, it is unclear why dengue remains an issue in affluent countries. a better understanding of dengue epidemiology and its burden, and those of chikungunya virus and zika virus which share vectors with dengue, is required to prevent the emergence of these diseases in high-income countries in the future. the purpose of this ...201627643596
west nile virus transmission: results from the integrated surveillance system in italy, 2008 to 2015.in italy a national plan for the surveillance of imported and autochthonous human vector-borne diseases (chikungunya, dengue, zika virus disease and west nile virus (wnv) disease) that integrates human and veterinary (animals and vectors) surveillance, is issued and revised annually according with the observed epidemiological changes. here we describe results of the wnv integrated veterinary and human surveillance systems in italy from 2008 to 2015. a real time data exchange protocol is in place ...027684046
the c-terminal 18 amino acid region of dengue virus ns5 regulates its subcellular localization and contains a conserved arginine residue essential for infectious virus production.dengue virus ns5 is the most highly conserved amongst the viral non-structural proteins and is responsible for capping, methylation and replication of the flavivirus rna genome. interactions of ns5 with host proteins also modulate host immune responses. although replication occurs in the cytoplasm, an unusual characteristic of denv2 ns5 is that it localizes to the nucleus during infection with no clear role in replication or pathogenesis. we examined ns5 of denv1 and 2, which exhibit the most pr ...201627622521
response: commentary: zika virus: the latest newcomer. 201627656170
zika virus is not uniquely stable at physiological temperatures compared to other flaviviruses.zika virus (zikv) is a flavivirus that has emerged as a global health threat due in part to its association with congenital abnormalities. other globally relevant flaviviruses include dengue virus (denv) and west nile virus (wnv). high-resolution structures of zikv reveal many similarities to denv and suggest some differences, including an extended glycan loop (d. sirohi, z. chen, l. sun, t. klose, t. c. pierson, et al., 352:467-470, 2016, http://dx.doi.org/10.1126/science.aaf5316) and unique in ...201627601578
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