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directional and reoccurring sequence change in zoonotic rna virus genomes visualized by time-series word count.ebolavirus, mers coronavirus and influenza virus are zoonotic rna viruses, which mutate very rapidly. viral growth depends on many host factors, but human cells may not provide the ideal growth conditions for viruses invading from nonhuman hosts. the present time-series analyses of short and long oligonucleotide compositions in these genomes showed directional changes in their composition after invasion from a nonhuman host, which are thought to recur after future invasions. in the recent west a ...201627808119
pyriproxyfen and the microcephaly epidemic in brazil - an ecological approach to explore the hypothesis of their association.the microcephaly epidemic in brazil generated intense debate regarding its causality, and one hypothesised cause of this epidemic, now recognised as congenital zika virus syndrome, was the treatment of drinking water tanks with pyriproxyfen to control aedes aegypti larvae. we present the results of a geographical analysis of the association between the prevalence of microcephaly confirmed by fenton growth charts and the type of larvicide used in the municipalities that were home to the mothers o ...201627812601
zika virus elicits p53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly and p53.epidemiological evidence from the current outbreak of zika virus (zikv) and recent studies in animal models indicate a strong causal link between zikv and microcephaly. zikv infection induces cell-cycle arrest and apoptosis in proliferating neural progenitors. however, the mechanisms leading to these phenotypes are still largely obscure. in this report, we explored the possible similarities between transcriptional responses induced by zikv in human neural progenitors and those elicited by three ...201627787521
online platform for applying space-time scan statistics for prospectively detecting emerging hot spots of dengue fever.cases of dengue fever have increased in areas of southeast asia in recent years. taiwan hit a record-high 42,856 cases in 2015, with the majority in southern tainan and kaohsiung cities. leveraging spatial statistics and geo-visualization techniques, we aim to design an online analytical tool for local public health workers to prospectively identify ongoing hot spots of dengue fever weekly at the village level.201627884135
the ebola outbreak: catalyzing a "shift" in global health governance?as the 2014 ebola virus disease outbreak (evd) transitions to its post-endemic phase, its impact on the future of global public health, particularly the world health organization (who), is the subject of continued debate. criticism of who's performance grew louder in the outbreak's wake, placing this international health un-specialized agency in the difficult position of navigating a complex series of reform recommendations put forth by different stakeholders. decisions on who governance reform ...201627881085
efficacy of ulv and thermal aerosols of deltamethrin for control of aedes albopictus in nice, france.ultra-low volume (ulv) insecticidal aerosols dispensed from vehicle-mounted cold-foggers are widely considered the method of choice for control of aedes aegypti and ae. albopictus during outbreaks of dengue and chikungunya and, more recently, zika. nevertheless, their effectiveness has been poorly studied, particularly in europe. nearly all published studies of ulv efficacy are bio-assays based on the mortality of caged mosquitoes. in our study we preferred to monitor the direct impact of treatm ...201627881181
ebola, zika and the international health regulations - implications for port health preparedness.the outbreak of ebola virus disease in west africa in 2014-2015 was unprecedented in terms of its scale and consequence.  this, together with the emergence of zika virus as a public health emergency of international concern in 2016, has again highlighted the potential for disease to spread across international borders and provided an impetus for countries to review their port health preparedness. this report reviews the legislative framework and actions taken under this framework in advancing an ...201627871327
akirin2 is essential for the formation of the cerebral cortex.the proper spatial and temporal regulation of dorsal telencephalic progenitor behavior is a prerequisite for the formation of the highly-organized, six-layered cerebral cortex. premature differentiation of cells, disruption of cell cycle timing, excessive apoptosis, and/or incorrect neuronal migration signals can have devastating effects, resulting in a number of neurodevelopmental disorders involving microcephaly and/or lissencephaly. though genes encoding many key players in cortical developme ...201627871306
assessment of icount software, a precise and fast egg counting tool for the mosquito vector aedes aegypti.widespread in the tropics, the mosquito aedes aegypti is an important vector of many viruses, posing a significant threat to human health. vector monitoring often requires fecundity estimation by counting eggs laid by female mosquitoes. traditionally, manual data analyses have been used but this requires a lot of effort and is the methods are prone to errors. an easy tool to assess the number of eggs laid would facilitate experimentation and vector control operations.201627863526
a case series of atypical presentation of zika virus infection in singapore.the world health organization's and centers for disease control and prevention's definition of zika infection are symptoms of fever, rash, joint pain, myalgia, headache and conjunctivitis. the diagnosis of zika infection is based on the clinical history, physical examination and laboratory investigations which includes blood and urine zika virus polymerase chain reaction.201627855636
an insecticide resistance-breaking mosquitocide targeting inward rectifier potassium channels in vectors of zika virus and malaria.insecticide resistance is a growing threat to mosquito control programs around the world, thus creating the need to discover novel target sites and target-specific compounds for insecticide development. emerging evidence suggests that mosquito inward rectifier potassium (kir) channels represent viable molecular targets for developing insecticides with new mechanisms of action. here we describe the discovery and characterization of vu041, a submicromolar-affinity inhibitor of anopheles (an.) gamb ...201627849039
the impact of heterogeneity and awareness in modeling epidemic spreading on multiplex networks.in the real world, dynamic processes involving human beings are not disjoint. to capture the real complexity of such dynamics, we propose a novel model of the coevolution of epidemic and awareness spreading processes on a multiplex network, also introducing a preventive isolation strategy. our aim is to evaluate and quantify the joint impact of heterogeneity and awareness, under different socioeconomic conditions. considering, as case study, an emerging public health threat, zika virus, we intro ...201627848978
hiv and zika: when will we be able to end these epidemics? 201627846847
current medical research funding and frameworks are insufficient to address the health risks of global environmental change.three major international agreements signed in 2015 are key milestones for transitioning to more sustainable and resilient societies: the un 2030 agenda for sustainable development; the sendai framework for disaster risk reduction; and the paris agreement under the united nations framework convention on climate change. together, these agreements underscore the critical importance of understanding and managing the health risks of global changes, to ensure continued population health improvements ...201627835959
zika virus may affect the universal two-child policy: a new challenge for china. 201627832058
developing a vaccine against zika. 201627834272
three-dimensional rotating wall vessel-derived cell culture models for studying virus-host interactions.the key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3d) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. a lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. conventional monolayer cell cultures may support viral infection, but are unable to form the tiss ...201627834891
comparative genomics of beauveria bassiana: uncovering signatures of virulence against mosquitoes.entomopathogenic fungi such as beauveria bassiana are promising biological agents for control of malaria mosquitoes. indeed, infection with b. bassiana reduces the lifespan of mosquitoes in the laboratory and in the field. natural isolates of b. bassiana show up to 10-fold differences in virulence between the most and the least virulent isolate. in this study, we sequenced the genomes of five isolates representing the extremes of low/high virulence and three rna libraries, and applied a genome c ...201627905873
tracking insecticide resistance in mosquito vectors of arboviruses: the worldwide insecticide resistance network (win). 201627906961
human igg antibody response to aedes nterm-34kda salivary peptide, an epidemiological tool to assess vector control in chikungunya and dengue transmission area.arboviral diseases are an important public health concerns. vector control remains the sole strategy to fight against these diseases. because of the important limits of methods currently used to assess human exposure to aedes mosquito bites, much effort is being devoted to develop new indicators. recent studies have reported that human antibody (ab) responses to aedes aegypti nterm-34kda salivary peptide represent a promising biomarker tool to evaluate the human-aedes contact. the present study ...201627906987
peering below the diffraction limit: robust and specific sorting of viruses with flow cytometry.viruses are incredibly diverse organisms and impact all forms of life on earth; however, individual virions are challenging to study due to their small size and mass, precluding almost all direct imaging or molecular analysis. moreover, like microbes, the overwhelming majority of viruses cannot be cultured, impeding isolation, replication, and study of interesting new species. here, we introduce pcr-activated virus sorting, a method to isolate specific viruses from a heterogeneous population. sp ...201627906039
carrion's disease: an eradicable illness?carrion's disease is a neglected tropical disease caused by bartonella bacilliformis, a vector-borne pathogen restricted to the andean valleys of peru, ecuador and colombia. carrion's disease is a biphasic illness; in the acute phase the case-fatality rate can be as high as 88 %, related to high parasitemia, arriving to almost all erythrocytes, and secondary bacterial infections close related with the development of transient immunosuppression in the earlier illness phases. in addition, there ar ...201627903286
zika virus cell tropism in the developing human brain and inhibition by azithromycin.the rapid spread of zika virus (zikv) and its association with abnormal brain development constitute a global health emergency. congenital zikv infection produces a range of mild to severe pathologies, including microcephaly. to understand the pathophysiology of zikv infection, we used models of the developing brain that faithfully recapitulate the tissue architecture in early to midgestation. we identify the brain cell populations that are most susceptible to zikv infection in primary human tis ...201627911847
discovery of methylfarnesoate as the annelid brain hormone reveals an ancient role of sesquiterpenoids in reproduction.animals require molecular signals to determine when to divert resources from somatic functions to reproduction. this decision is vital in animals that reproduce in an all-or-nothing mode, such as bristle worms: females committed to reproduction spend roughly half their body mass for yolk and egg production; following mass spawning, the parents die. an enigmatic brain hormone activity suppresses reproduction. we now identify this hormone as the sesquiterpenoid methylfarnesoate. methylfarnesoate s ...201627894418
towards equity in health: researchers take stock.for the 2016 end-of-the-year editorial, the plos medicine editors asked 7 global health leaders to discuss developments relevant to the equitable provision of medical care to all populations. the result is a collection of expert views on ethical trial design, research during outbreaks, high-burden infectious diseases, diversity in research and protection of migrants.201627898673
military-civilian cooperative emergency response to infectious disease prevention and control in china.in recent years, the incidence of severe infectious diseases has increased, and the number of emerging infectious diseases continues to increase. the chinese government and military forces have paid a great deal of attention to infectious disease prevention and control, and using military-civilian cooperation, they have successfully prevented numerous severe epidemic situations, such as severe acute respiratory syndrome (sars), influenza a (h1n1), avian influenza h5n1 and h7n9, and ebola hemorrh ...201628050261
plasmodium vivax landscape in brazil: scenario and challenges.brazil is the largest country of latin america, with a considerable portion of its territoritory within the malaria-endemic amazon region in the north. furthermore, a considerable portion of its territory is located within the amazon region in the north. as a result, brazil has reported half of the total malaria cases in the americas in the last four decades. recent progress in malaria control has been accompanied by an increasing proportion of plasmodium vivax, underscoring a need for a better ...201627708190
zika travel policies may reduce women's leadership in global health. 201628031307
social mobilization and community engagement central to the ebola response in west africa: lessons for future public health emergencies.following the world health organization (who) declaration of a public health emergency of international concern regarding the ebola outbreak in west africa in july 2014, unicef was asked to co-lead, in coordination with who and the ministries of health of affected countries, the communication and social mobilization component-which unicef refers to as communication for development (c4d)-of the ebola response. for the first time in an emergency setting, c4d was formally incorporated into each cou ...201628031301
zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells.zika virus (zikv) infection has been associated with severe complications both in the developing and adult nervous system. to investigate the deleterious effects of zikv infection, we used human neural progenitor cells (npc), derived from induced pluripotent stem cells (ipsc). we found that npc are highly susceptible to zikv and the infection results in cell death. zikv infection led to a marked reduction in cell proliferation, ultrastructural alterations and induction of autophagy. induction of ...201628008958
atg16l1 governs placental infection risk and preterm birth in mice and women.the placenta is a barrier against maternal-fetal transmission of pathogens. placental infections can cause several adverse pregnancy outcomes, including preterm birth (ptb). yet, we have limited knowledge regarding the mechanisms the placenta uses to control infections. here, we show that autophagy, a cellular recycling pathway important for host defense against pathogens, and the autophagy gene atg16l1 play a key role in placental defense and are negatively associated with ptb in pregnant women ...201628018968
simple reverse genetics systems for asian and african zika viruses.zika virus (zikv), a typical example of a re-emerging pathogen, recently caused large outbreaks in pacific islands and the americas, associated with congenital diseases and neurological complications. deciphering the natural history, ecology and pathophysiology of this mosquito-borne pathogen requires effective reverse genetics tools. in the current study, using the bacterium-free 'infectious subgenomic amplicons' (isa) method, we generated and made available to the scientific community via the ...201627991555
modernising epidemic science: enabling patient-centred research during epidemics.emerging and epidemic infectious disease outbreaks are a significant public health problem and global health security threat. as an outbreak begins, epidemiological investigations and traditional public health responses are generally mounted very quickly. however, patient-centred research is usually not prioritised when planning and enacting the response. instead, the clinical research response occurs subsequent to and separate from the public health response, and is inadequate for evidence-base ...201627989237
contraceptive sales in the setting of the zika virus epidemic.has there been any influence of the zika virus (zikv) outbreak on the sales of contraceptive methods in brazil?201627932442
dishing out mini-brains: current progress and future prospects in brain organoid research.the ability to model human brain development in vitro represents an important step in our study of developmental processes and neurological disorders. protocols that utilize human embryonic and induced pluripotent stem cells can now generate organoids which faithfully recapitulate, on a cell-biological and gene expression level, the early period of human embryonic and fetal brain development. in combination with novel gene editing tools, such as crispr, these methods represent an unprecedented m ...201627402594
perspectives on the role of mobility, behavior, and time scales in the spread of diseases.the dynamics, control, and evolution of communicable and vector-borne diseases are intimately connected to the joint dynamics of epidemiological, behavioral, and mobility processes that operate across multiple spatial, temporal, and organizational scales. the identification of a theoretical explanatory framework that accounts for the pattern regularity exhibited by a large number of host-parasite systems, including those sustained by host-vector epidemiological dynamics, is but one of the challe ...201627965394
estimation of zika virus prevalence by appearance of microcephaly.there currently is a severe zika virus (zikv) epidemic in brazil and other south american countries. due to international travel, this poses severe public health risk of zikv importation to other countries. we estimate the prevalence of zikv in an import region by the time a microcephaly case is detected, since microcephaly is presently the most significant indication of zikv presence.201627955630
rapid, affordable and portable medium-throughput molecular device for zika virus.zika virus (zikv) has gained global attention as an etiologic agent of fetal microcephaly and guillain-barré syndrome. existing immuno-based rapid tests often fail to distinguish between zika and related flaviviruses that are common in affected regions of central and south americas and the caribbean. the us cdc and qualified state health department laboratories can perform the reverse transcription polymerase chain reaction (rt-pcr) zikv test using highly sophisticated instruments with long turn ...201627934884
a historic report of zika in mozambique: implications for assessing current risk. 201627930650
public health interventions for aedes control in the time of zikavirus- a meta-review on effectiveness of vector control strategies.there is renewed interest in effective measures to control zika and dengue vectors. a synthesis of published literature with a focus on the quality of evidence is warranted to determine the effectiveness of vector control strategies.201627926934
the self-regulation model of illness: comparison between zika and dengue and its application to predict mosquito prevention behaviours in malaysia, a dengue-endemic country.perceptions about illnesses may influence self-care and preventive health behaviours. illness perceptions of the zika virus (zikv) infection were investigated under the framework of the self-regulation model of illness. illness perception differences between zikv and dengue fever were also examined. lastly, associations between illness perceptions of zikv with mosquito prevention practices were studied. samples were drawn from landline telephone numbers using computer-assisted telephone intervie ...201627929451
deep sequencing of the 16s ribosomal rna of the neonatal oral microbiome: a comparison of breast-fed and formula-fed infants.in utero and upon delivery, neonates are exposed to a wide array of microorganisms from various sources, including maternal bacteria. prior studies have proposed that the mode of feeding shapes the gut microbiota and, subsequently the child's health. however, the effect of the mode of feeding and its influence on the development of the neonatal oral microbiota in early infancy has not yet been reported. the aim of this study was to compare the oral microbiota of healthy infants that were exclusi ...201627922070
effective risk governance requires risk communication experts. 201627919122
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
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
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
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
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
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
a comprehensive systems biology approach to studying zika virus.zika virus (zikv) is responsible for an ongoing and intensifying epidemic in the western hemisphere. we examined the complete predicted proteomes, glycomes, and selectomes of 33 zikv strains representing temporally diverse members of the african lineage, the asian lineage, and the current outbreak in the americas. derivation of the complete selectome is an 'omics' approach to identify distinct evolutionary pressures acting on different features of an organism. employment of the m8 model did not ...201627584813
zika virus: a new animal model for an arbovirus. 201627149628
zika virus outbreak in rio de janeiro, brazil: clinical characterization, epidemiological and virological aspects.in 2015, brazil was faced with the cocirculation of three arboviruses of major public health importance. the emergence of zika virus (zikv) presents new challenges to both clinicians and public health authorities. overlapping clinical features between diseases caused by zikv, dengue (denv) and chikungunya (chikv) and the lack of validated serological assays for zikv make accurate diagnosis difficult.201627070912
flavivirus vaccines: innovate, invest, implement. 201627211530
neglected tropical diseases in the anthropocene: the cases of zika, ebola, and other infections. 201627058728
a full-length infectious cdna clone of zika virus from the 2015 epidemic in brazil as a genetic platform for studies of virus-host interactions and vaccine development.an arthropod-borne virus, zika virus (zikv), has recently emerged as a major human pathogen. associated with complications during perinatal development and guillain-barré syndrome in adults, zikv raises new challenges for understanding the molecular determinants of flavivirus pathogenesis. this underscores the necessity for the development of a reverse genetic system based on an epidemic zikv strain. here, we describe the generation and characterization in cell cultures of an infectious cdna clo ...201627555311
oligomeric viral proteins: small in size, large in presence.viruses are obligate parasites that rely heavily on host cellular processes for replication. the small number of proteins typically encoded by a virus is faced with selection pressures that lead to the evolution of distinctive structural properties, allowing each protein to maintain its function under constraints such as small genome size, high mutation rate, and rapidly changing fitness conditions. one common strategy for this evolution is to utilize small building blocks to generate protein ol ...201627685368
inhibition of protein kinase c promotes dengue virus replication.dengue virus (denv) is a member of the flaviviridae family, transmitted to human via mosquito. denv infection is common in tropical areas and occasionally causes life-threatening symptoms. denv contains a relatively short positive-stranded rna genome, which encodes ten viral proteins. thus, the viral life cycle is necessarily rely on or regulated by host factors.201626931565
consortia's critical role in developing medical countermeasures for re-emerging viral infections: a usa perspective.viral infections, such as ebola, severe acute respiratory syndrome/middle east respiratory syndrome and west nile virus have emerged as a serious health threat with no effective therapies. these infections have little commercial potential and are not a high priority for the pharmaceutical industry. however, the academic community has been active in this area for many years. the challenge is how to take this academic virology knowledge into a drug discovery and development domain. one approach is ...201627325914
kissing-loop interaction between 5' and 3' ends of tick-borne langat virus genome 'bridges the gap' between mosquito- and tick-borne flaviviruses in mechanisms of viral rna cyclization: applications for virus attenuation and vaccine development.insertion of microrna target sequences into the flavivirus genome results in selective tissue-specific attenuation and host-range restriction of live attenuated vaccine viruses. however, previous strategies for mirna-targeting did not incorporate a mechanism to prevent target elimination under mirna-mediated selective pressure, restricting their use in vaccine development. to overcome this limitation, we developed a new approach for mirna-targeting of tick-borne flavivirus (langat virus, lgtv) i ...201626850640
hypothalamus-pituitary-adrenal cell-mediated immunity regulation in the immune restoration inflammatory syndrome.over one third of the patients sero-positive for the human immunodeficiency virus (hiv) with signs of the acquired immune deficiency syndrome (aids), and under treatment with anti-retroviral therapy (art), develop the immune reconstitution inflammatory syndrome (iris). it is not clear what variables are that determine whether a patient with hiv/aids will develop art-related iris, but the best evidence base thus far indicates that hiv/aids patients with low cd4 cell count, and hiv/aids patients w ...201627212842
potent allosteric dengue virus ns5 polymerase inhibitors: mechanism of action and resistance profiling.flaviviruses comprise major emerging pathogens such as dengue virus (denv) or zika virus (zikv). the flavivirus rna genome is replicated by the rna-dependent-rna polymerase (rdrp) domain of non-structural protein 5 (ns5). this essential enzymatic activity renders the rdrp attractive for antiviral therapy. ns5 synthesizes viral rna via a "de novo" initiation mechanism. crystal structures of the flavivirus rdrp revealed a "closed" conformation reminiscent of a pre-initiation state, with a well ord ...201627500641
navigating the zika panic.the epidemics of ebola virus in west africa and zika virus in america highlight how viruses can explosively emerge into new territories. these epidemics also exposed how unprepared we are to handle infectious disease emergencies. this is also true when we consider hypothesized new clinical features of infection, such as the associations between zika virus infection and severe neurological disease, including microcephaly and guillain-barré syndrome. on the surface, these pathologies appear to be ...201627746903
preventing zika virus infection during pregnancy using a seasonal window of opportunity for conception.it has come to light that zika virus (zikv) infection during pregnancy can result in trans-placental transmission to the fetus along with fetal death, congenital microcephaly, and/or central nervous system (cns) malformations. there are projected to be >9,200,000 births annually in countries with ongoing zikv transmission. in response to the zikv threat, the world health organization (who) is strategically targeting prevention of infection in pregnant women and funding contraception in epidemic ...201627467271
selective factors associated with the evolution of codon usage in natural populations of arboviruses.arboviruses (arthropod borne viruses) have life cycles that include both vertebrate and invertebrate hosts with substantial differences in vector and host specificity between different viruses. most arboviruses utilize rna for their genetic material and are completely dependent on host trnas for their translation, suggesting that virus codon usage could be a target for selection. in the current study we analyzed the relative synonymous codon usage (rscu) patterns of 26 arboviruses together with ...201627455096
inflammation thread runs across medical laboratory specialities.we work on the assumption that four major specialities or sectors of medical laboratory assays, comprising clinical chemistry, haematology, immunology, and microbiology, embraced by genome sequencing techniques, are routinely in use. medical laboratory markers for inflammation serve as model: they are allotted to most fields of medical lab assays including genomics. incessant coding of assays aligns each of them in the long lists of big data. as exemplified with the complement gene family, conta ...201627493451
biodiversity and temporal distribution of immature culicidae in the atlantic forest, rio de janeiro state, brazil.to increase the knowledge of biodiversity and identify larval habitats used by immature mosquitoes in the atlantic forest, we conducted a study in areas with various stages of preservation within the guapiaçu ecological reserve in cachoeiras de macacu, rio de janeiro state. the culicidae fauna were sampled during february, april, june, august, october, and december 2012; february, march, april, may, june, august, october, and december 2013; and january and march 2014. immature mosquitoes were co ...201627404496
composition and genetic diversity of mosquitoes (diptera: culicidae) on islands and mainland shores of kenya's lakes victoria and baringo.the lake baringo and lake victoria regions of kenya are associated with high seroprevalence of mosquito-transmitted arboviruses. however, molecular identification of potential mosquito vector species, including morphologically identified ones, remains scarce. to estimate the diversity, abundance, and distribution of mosquito vectors on the mainland shores and adjacent inhabited islands in these regions, we collected and morphologically identified adult and immature mosquitoes and obtained the co ...201627402888
surveillance of mosquitoes and selected arthropod-borne viruses in the context of milan expo 2015.from 1 may 2015 to 31 october 2015 over 20 million visitors from all over the world visited the universal exhibition (expo) hosted by milan (lombardy region, italy), raising concerns about the possible introduction of mosquito-borne diseases from endemic countries. the entomological surveillance protocol performed in lombardy over the last three years was implemented in the expo area and in the two major regional airports using both center for disease control co₂ and biogents sentinel traps. thi ...201627399756
inhibitory antibodies targeting emerging viruses: advancements and mechanisms.from ebola virus outbreaks in western africa to the introduction of chikungunya and zika viruses in the americas, new and neglected viruses continue to emerge and spread around the world. due to a lack of existing vaccines or specific therapeutics, little other than supportive care and attempts to interrupt transmission can be provided during initial outbreaks. this has prompted a shift in vaccine design and development to identify novel epitopes and mechanisms of protection that may offer a bro ...201627226280
zika virus: an emergence of a new arbovirus.the world is facing a new pandemic in progress due to a mosquito-borne flavivirus popularly known as zika virus. the emergence of this new virus is really alarming with the sudden increment in the cases of microcephaly reported from brazil. the findings attributing the involvement of zika virus as the reason for congenital deformations in the babies born in afflicted areas have really shocked the world. the present knowledge about this virus is very limited and in the absence of further studies ...201627630846
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
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