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discovery of host-targeted covalent inhibitors of dengue virus.we report here on an approach targeting the host reactive cysteinome to identify inhibitors of host factors required for the infectious cycle of flaviviruses and other viruses. we used two parallel cellular phenotypic screens to identify a series of covalent inhibitors, exemplified by ql-xii-47, that are active against dengue virus. we show that the compounds effectively block viral protein expression and that this inhibition is associated with repression of downstream processes of the infectiou ...201728034743
zika virus methyltransferase: structure and functions for drug design perspectives.the flavivirus zika virus (zikv) is the causal agent of neurological disorders like microcephaly in newborns or guillain-barre syndrome. its ns5 protein embeds a methyltransferase (mtase) domain involved in the formation of the viral mrna cap. we investigated the structural and functional properties of the zikv mtase. we show that the zikv mtase can methylate rna cap structures at the n-7 position of the cap, and at the 2'-o position on the ribose of the first nucleotide, yielding a cap-1 struct ...201728031359
morphological studies on adult mosquitoes (diptera: culicidae) and first report of the potential zika virus vector aedes (stegomyia) unilineatus (theobald, 1906) in iran.beside numerous extensive studies on anophelinae mosquitoes of iran, little is known on aedes species in the country and existing reports are dispersed. the objective of this study was to identify adults of culicinae species occurring in the sistan and baluchestan province, southeast of iran, during 2012-2014. mosquito collections were carried out three times (may-june, september, october-november) in four counties by centers for diseases control (cdc) light traps and human landing catches outdo ...201628028709
molecular determinants of human neutralizing antibodies isolated from a patient infected with zika virus.the 2015-2016 outbreak of zika virus (zikv) disease has affected many countries and is a major public health concern. zikv is associated with fetal microcephaly and neurological complications, and countermeasures are needed to treat and prevent zikv infection. we report the isolation of 13 specific human monoclonal antibodies from a single patient infected with zikv. two of the isolated antibodies (z23 and z3l1) demonstrated potent zikv-specific neutralization in vitro without binding or neutral ...201627974667
zika virus infection of hofbauer cells.recent studies have linked antenatal infection with zika virus (zikv) with major adverse fetal and neonatal outcomes, including microcephaly. there is a growing consensus for the existence of a congenital zika syndrome (czs). previous studies have indicated that non-placental macrophages play a key role in the replication of dengue virus (denv), a closely related flavivirus. as the placenta provides the conduit for vertical transmission of certain viruses, and placental hofbauer cells (hbcs) are ...201727966815
based on the risk of dengue virus transmission via blood transfusion: what about the risk in case of zika virus? 201627890376
comparative genome analysis between southeast asian and south american zika viruses.to understand the cause for the differences between potentially mild southeast asian and the more pathogenic zikv in south america.201627890363
antiviral activities of selected antimalarials against dengue virus type 2 and zika virus.in a previous study, twelve antimalarial compounds, amodiaquine (aq) and derivatives, were shown to have potent anti-dengue viral (denv) activity by using the stable denv2 renilla luciferase reporter replicon expressing bhk-21 cells, infectivity (plaque), and the qrt-pcr assays. in this study, we performed molecular modeling on these compounds to determine their stereo-electronic properties required for optimal antiviral activity. based on the similarity of calculated stereo-electronic profiles, ...201727889529
the many faces of the flavivirus ns5 protein in antagonism of type i interferon signaling.the vector-borne flaviviruses cause severe disease in humans on every inhabited continent on earth. their transmission by arthropods, particularly mosquitoes, facilitates large emergence events such as witnessed with zika virus (zikv) or west nile virus in the americas. every vector-borne flavivirus examined thus far that causes disease in humans, from dengue virus to zikv, antagonizes the host type i interferon (ifn-i) response by preventing jak-stat signaling, suggesting that suppression of th ...201727881649
structure of the ns5 methyltransferase from zika virus and implications in inhibitor design.recent outbreak of flavivirus zika virus (zikv) in america has urged the basic as well as translational studies of this important human pathogen. the nonstructural protein 5 (ns5) of the flavivirus has an n-terminal methyltransferase (mtase) domain that plays critical roles in viral rna genome capping. the null mutant of ns5 mtase is lethal for virus. therefore, ns5 is a potential drug target for the treatment of zika virus infection. in this study, we determined crystal structures of the zikv m ...201627866982
green synthesized nanoparticles in the fight against mosquito-borne diseases and cancer-a brief review.nanobiomedicine and parasitology are facing a number of key challenges, which mostly deal with the paucity of effective preventive and curative tools against mosquito-borne diseases and cancer. in this scenario, the employ of botanical and invertebrate extracts as reducing, stabilizing and capping agents for the synthesis of nanoparticles is advantageous over chemical and physical methods, since it is one-pot, cheap, and does not require high pressure, energy, temperature, or the use of highly t ...201627866627
zika virus infection during the olympic games in rio: a fear or an actual risk?the recent outbreak of zika virus infection in brazil has aroused considerable media interest due to its association with neurological malformations in children born from mothers infected by the virus and to its association with guillain-barre syndrome in adults. this relationship has led to the world health organisation declaring the current epidemic as a "public health emergency of international concern". controversy also emerged on the advisability of delaying or changing the location of the ...201727865425
investigation of a guillain-barré syndrome cluster in the republic of fiji.in 2014, we investigated a cluster of guillain-barre syndrome (gbs) in fiji that occurred during a dengue epidemic. we designed a case-control study to determine the etiology.201727842986
magnetic nanoparticles are highly toxic to chloroquine-resistant plasmodium falciparum, dengue virus (den-2), and their mosquito vectors.a main challenge in parasitology is the development of reliable tools to prevent or treat mosquito-borne diseases. we investigated the toxicity of magnetic nanoparticles (mnp) produced by magnetospirillum gryphiswaldense (strain msr-1) on chloroquine-resistant (cq-r) and sensitive (cq-s) plasmodium falciparum, dengue virus (den-2), and two of their main vectors, anopheles stephensi and aedes aegypti, respectively. mnp were studied by fourier-transform infrared spectroscopy and transmission elect ...201727815736
zika in pernambuco: rewriting the first outbreak.a zika virus epidemic was registered in 2015 in northeast brazil. in the state of pernambuco, thousands of classical cases transpired, and in the following months, neurological disturbances in adults and microcephaly in newborns emerged as complications. after the peak of the epidemic, the official system reported only four cases of zika virus but over 100,000 cases of dengue virus. the vigilance system was unable to retrospectively estimate cases or to issue an alert to officially notified case ...201627812648
lipids and flaviviruses, present and future perspectives for the control of dengue, zika, and west nile viruses.flaviviruses are emerging arthropod-borne pathogens that cause life-threatening diseases such as yellow fever, dengue, west nile encephalitis, tick-borne encephalitis, kyasanur forest disease, tick-borne encephalitis, or zika disease. this viral genus groups >50 viral species of small enveloped plus strand rna virus that are phylogenetically closely related to hepatitis c virus. importantly, the flavivirus life cycle is intimately associated to host cell lipids. along this line, flaviviruses rea ...201627702593
tim-1 promotes hepatitis c virus cell attachment and infection.human tim and tam family proteins were recently found to serve as phosphatidylserine (ps) receptors which promote infections by many different viruses, including dengue virus, west nile virus, ebola virus, marburg virus, and zika virus. in the present study, we provide substantial evidence demonstrating that tim-1 is important for efficient infection by hepatitis c virus (hcv). the knockdown of tim-1 expression significantly reduced hcv infection but not hcv rna replication. likewise, tim-1 knoc ...201727807228
zika virus infection damages the testes in mice.infection of pregnant women with zika virus (zikv) can cause congenital malformations including microcephaly, which has focused global attention on this emerging pathogen. in addition to transmission by mosquitoes, zikv can be detected in the seminal fluid of affected males for extended periods of time and transmitted sexually. here, using a mouse-adapted african zikv strain (dakar 41519), we evaluated the consequences of infection in the male reproductive tract of mice. we observed persistence ...201627798603
guillain-barré syndrome associated with zika virus infection in colombia.background zika virus (zikv) infection has been linked to the guillain-barré syndrome. from november 2015 through march 2016, clusters of cases of the guillain-barré syndrome were observed during the outbreak of zikv infection in colombia. we characterized the clinical features of cases of guillain-barré syndrome in the context of this zikv infection outbreak and investigated their relationship with zikv infection. methods a total of 68 patients with the guillain-barré syndrome at six colombian ...201627705091
coinfection with zika and dengue-2 viruses in a traveler returning from haiti, 2016: clinical presentation and genetic analysis.zika virus and dengue virus serotype 2 were isolated from a patient with travel to haiti who developed fever, rash, arthralgias, and conjunctivitis. the infecting zika virus was related to venezuelan and brazilian strains but evolved along a lineage originating from strains isolated in 2014 in the same region of haiti.201727694479
noncoding subgenomic flavivirus rna is processed by the mosquito rna interference machinery and determines west nile virus transmission by culex pipiens mosquitoes.flaviviruses, such as zika virus, yellow fever virus, dengue virus, and west nile virus (wnv), are a serious concern for human health. flaviviruses produce an abundant noncoding subgenomic flavivirus rna (sfrna) in infected cells. sfrna results from stalling of the host 5'-3' exoribonuclease xrn1/pacman on conserved rna structures in the 3' untranslated region (utr) of the viral genomic rna. sfrna production is conserved in insect-specific, mosquito-borne, and tick-borne flaviviruses and flavivi ...201627581979
a sensitive virus yield assay for evaluation of antivirals against zika virus.despite the rapid spread of zika virus (zikv) infection and associated neurological complications in the america's, prophylactic or therapeutic countermeasures are not currently available. this is mostly due to the fact that until recently there was no presumed need for medical intervention since there was no association between zikv infection and significant human morbidity. consequently, there are currently no tools due mostly to the lack of sensitive cell based assays amenable for identificat ...201627678028
cd4(+) and cd8(+) t-cell immunity to dengue - lessons for the study of zika virus.dengue virus (denv) and zika virus (zikv) are rapidly emerging mosquito-borne flaviviruses that represent a public health concern. understanding host protective immunity to these viruses is critical for the design of optimal vaccines. over a decade of research has highlighted a significant contribution of the t-cell response to both protection and/or disease enhancement during denv infection, the latter being mainly associated with sub-optimal cross-reactive t-cell responses during secondary inf ...201727763656
expanded dengue.the world health organization (who) has coined the term expanded dengue to describe cases which do not fall into either dengue shock syndrome or dengue hemorrhagic fever. this has incorporated several atypical findings of dengue. dengue virus has not been enlisted as a common etiological agent in several conditions like encephalitis, guillain barre syndrome. moreover it is a great mimic of co-existing epidemics like malaria, chikungunya and zika virus disease, which are also mosquito-borne disea ...201627759344
zika virus (zikv) infection related with immune thrombocytopenic purpura (itp) exacerbation and antinuclear antibody positivity.a 30-year-old colombian woman with past history of immune thrombocytopenia (itp) presented to the emergency room with two days of global headache, arthralgia, myalgia, and low level fever and generalized erythematous rash. platelets dropped to 9 × 10(9)/l (fourth day of symptoms) without hemorrhagic manifestations but recovered to 30 × 10(9)/l in 24 hours (fifth day). dengue virus infection, as well as other viral infections, was ruled out. zika virus (zikv) was evaluated in serum and urine samp ...201627694629
zika virus infection induces cranial neural crest cells to produce cytokines at levels detrimental for neurogenesis.zika virus (zikv) infection during pregnancy is linked to microcephaly, which is attributed to infection of developing brain structures. zikv infects neural progenitor cells in vitro, though its effects on other developmentally relevant stem cell populations, including cranial neural crest cells (cnccs), have not been assessed. cnccs give rise to most cranial bones and exert paracrine effects on the developing brain. here, we report that cnccs are productively infected by zikv, but not by the re ...201627693308
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 ...201627652985
association between zika virus infection and microcephaly in brazil, january to may, 2016: preliminary report of a case-control study.the microcephaly epidemic, which started in brazil in 2015, was declared a public health emergency of international concern by who in 2016. we report the preliminary results of a case-control study investigating the association between microcephaly and zika virus infection during pregnancy.201627641777
dengue antibody and zika: friend or foe?zika virus is a mosquito-borne flavivirus related to dengue that is rapidly spreading through the americas. this outbreak is occurring in dengue-endemic areas where the population has acquired antibodies to dengue. recent studies reveal that preexisting dengue antibodies may have opposite effects on zika infection, transmission, and clinical outcome. discerning these effects is critical to a better understanding of zika pathogenesis and the prevention of future outbreaks.201627599407
dengue virus perturbs mitochondrial morphodynamics to dampen innate immune responses.with no antiviral drugs or widely available vaccines, dengue virus (denv) constitutes a public health concern. denv replicates at er-derived cytoplasmic structures that include substructures called convoluted membranes (cms); however, the purpose of these membrane alterations remains unclear. we determine that denv nonstructural protein (ns)4b, a promising drug target with unknown function, associates with mitochondrial proteins and alters mitochondria morphology to promote infection. during inf ...201627545046
zika virus ns4a and ns4b proteins deregulate akt-mtor signaling in human fetal neural stem cells to inhibit neurogenesis and induce autophagy.the current widespread outbreak of zika virus (zikv) infection has been linked to severe clinical birth defects, particularly microcephaly, warranting urgent study of the molecular mechanisms underlying zikv pathogenesis. akt-mtor signaling is one of the key cellular pathways essential for brain development and autophagy regulation. here, we show that zikv infection of human fetal neural stem cells (fnscs) causes inhibition of the akt-mtor pathway, leading to defective neurogenesis and aberrant ...201627524440
zika virus-induced antibody response enhances dengue virus serotype 2 replication in vitro.zika virus has emerged in the americas, where dengue virus is endemic. among the 4 serotypes of dengue virus, antibody-dependent enhancement is thought to enhance viral replication and disease severity. reports suggest that anti-dengue virus antibody may enhance zika virus replication. we investigated whether zika virus antibodies enhance dengue virus replication, by exposing c57bl/6 mice to zika virus. polyclonal serum was verified for strong zika virus-neutralizing, dengue virus-subneutralizin ...201627521359
inhibition of the membrane attack complex by dengue virus ns1 through interaction with vitronectin and terminal complement proteins.dengue virus (denv) infects millions of people worldwide and is a major public health problem. denv nonstructural protein 1 (ns1) is a conserved glycoprotein that associates with membranes and is also secreted into the plasma in denv-infected patients. the present study describes a novel mechanism by which ns1 inhibits the terminal complement pathway. we first identified the terminal complement regulator vitronectin (vn) as a novel denv2 ns1 binding partner by using a yeast two-hybrid system. th ...201627512066
update: ongoing zika virus transmission - puerto rico, november 1, 2015-july 7, 2016.zika virus is a flavivirus transmitted primarily by aedes aegypti and aedes albopictus mosquitoes, and infection can be asymptomatic or result in an acute febrile illness with rash (1). zika virus infection during pregnancy is a cause of microcephaly and other severe birth defects (2). infection has also been associated with guillain-barré syndrome (gbs) (3) and severe thrombocytopenia (4,5). in december 2015, the puerto rico department of health (prdh) reported the first locally acquired case o ...201627490087
zika virus: a new arboviral public health problem.zika virus (zikv) is a single-stranded rna virus in the flaviviridae family and transmitted to human through infected mosquitos (aedes aegypti and aedes albopictus). virus is closely related with other flaviviruses; dengue virus, yellow fever virus, west nile virus, and japanese encephalitis virus phylogenetically. due to the possible relationship between virus and clinical features including microcephaly, ventricule, and eye deformities, guillain-barre syndrome increases the interest on this vi ...201627469112
specificity, cross-reactivity, and function of antibodies elicited by zika virus infection.zika virus (zikv), a mosquito-borne flavivirus with homology to dengue virus (denv), has become a public health emergency. by characterizing memory lymphocytes from zikv-infected patients, we dissected zikv-specific and denv-cross-reactive immune responses. antibodies to nonstructural protein 1 (ns1) were largely zikv-specific and were used to develop a serological diagnostic tool. in contrast, antibodies against e protein domain i/ii (edi/ii) were cross-reactive and, although poorly neutralizin ...201627417494
novel strategies for discovering inhibitors of dengue and zika fever. 201627401601
predicted pattern of zika virus infection distribution with reference to rainfall in thailand.zika virus infection is the present global medical problem. the disease appears in several countries around the world. the relationship between rainfall and occurrence of zika virus infection was previously mentioned. here, the authors use the mathematical modeling technique to reappraise on the previous data on immunoreactivity rate of zika virus, dengue virus and ckikungunya virus in thailand and the reported interrelationship between arboviral infections and rainfall in thailand for construct ...201627393105
zika virus infections: an overview of current scenario.zika virus (zikv) was discovered more than half a century ago, recently it has gained unprecedented attention by the global health community. until 2007, only 14 cases of human zikv infections were reported around the globe, while during the current outbreak, estimated cases mounted to approximately 1.5 million in brazil alone, the virus was disseminated to wider south-american territories and travel-associated zikv infections were reported in usa, europe and recently in china. zikv infections r ...201627393087
identification of zika virus and dengue virus dependency factors using functional genomics.the flaviviruses dengue virus (denv) and zika virus (zikv) are severe health threats with rapidly expanding ranges. to identify the host cell dependencies of denv and zikv, we completed orthologous functional genomic screens using rnai and crispr/cas9 approaches. the screens recovered the zikv entry factor axl as well as multiple host factors involved in endocytosis (rab5c and rabgef), heparin sulfation (ndst1 and ext1), and transmembrane protein processing and maturation, including the endoplas ...201627342126
structural basis of potent zika-dengue virus antibody cross-neutralization.zika virus is a member of the flavivirus genus that had not been associated with severe disease in humans until the recent outbreaks, when it was linked to microcephaly in newborns in brazil and to guillain-barré syndrome in adults in french polynesia. zika virus is related to dengue virus, and here we report that a subset of antibodies targeting a conformational epitope isolated from patients with dengue virus also potently neutralize zika virus. the crystal structure of two of these antibodies ...201627338953
clinical and spatial features of zika virus in mexico.zika virus (zikv) is an emerging arbovirus transmitted to humans by aedes mosquitoes, the same vectors that transmit dengue virus and chikungunya. recent work has suggested that prior infection with dengue could lead to more severe clinical disease in zikv patients. here, we describe the spatial distribution of and clinical symptoms experienced by zikv cases in mexico.201627311388
emerging role of zika virus in adverse fetal and neonatal outcomes.the rapid spread of the zika virus (zikv) in the americas and its potential association with thousands of suspected cases of microcephaly in brazil and higher rates of guillain-barré syndrome meet the conditions for a public health emergency of international concern, as stated by the world health organization in february 2016. two months later, the centers for disease control and prevention (cdc) announced that the current available evidence supports the existence of a causal relationship betwee ...201627281741
the ifitms inhibit zika virus replication.zika virus has emerged as a severe health threat with a rapidly expanding range. the ifitm family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses west nile virus and dengue virus. here, we show that ifitm1 and ifitm3 inhibit zika virus infection early in the viral life cycle. moreover, ifitm3 can prevent zika-virus-induced cell death. these results suggest that strategies to boost the actions and/or levels of the ifitms might ...201627268505
interim guidance for interpretation of zika virus antibody test results.zika virus is a single-stranded rna virus in the genus flavivirus and is closely related to dengue, west nile, japanese encephalitis, and yellow fever viruses (1,2). among flaviviruses, zika and dengue virus share similar symptoms of infection, transmission cycles, and geographic distribution. diagnostic testing for zika virus infection can be accomplished using both molecular and serologic methods. for persons with suspected zika virus disease, a positive real-time reverse transcription-polymer ...201627254248
zika virus targets human stat2 to inhibit type i interferon signaling.the ongoing epidemic of zika virus (zikv) illustrates the importance of flaviviruses as emerging human pathogens. all vector-borne flaviviruses studied thus far have to overcome type i interferon (ifn) to replicate and cause disease in vertebrates. the mechanism(s) by which zikv antagonizes ifn signaling is unknown. here, we report that the nonstructural protein ns5 of zikv and other flaviviruses examined could suppress ifn signaling, but through different mechanisms. zikv ns5 expression resulte ...201627212660
rapid, low-cost detection of zika virus using programmable biomolecular components.the recent zika virus outbreak highlights the need for low-cost diagnostics that can be rapidly developed for distribution and use in pandemic regions. here, we report a pipeline for the rapid design, assembly, and validation of cell-free, paper-based sensors for the detection of the zika virus rna genome. by linking isothermal rna amplification to toehold switch rna sensors, we detect clinically relevant concentrations of zika virus sequences and demonstrate specificity against closely related ...201627160350
dengue virus immunopathogenesis: lessons applicable to the emergence of zika virus.dengue is the leading mosquito-transmitted viral infection in the world. there are more than 390 million new infections annually; while the majority of infected individuals are asymptomatic or develop a self-limited dengue fever, up to 1 million clinical cases develop severe manifestations, including dengue hemorrhagic fever and shock syndrome, resulting in ~25,000 deaths annually, mainly in children. gaps in our understanding of the mechanisms that contribute to dengue infection and immunopatho ...201627130436
high specificity of a novel zika virus elisa in european patients after exposure to different flaviviruses.the current zika virus (zikv) epidemic in the americas caused an increase in diagnostic requests in european countries. here we demonstrate high specificity of the euroimmun anti-zikv igg and igm elisa tests using putative cross-reacting sera of european patients with antibodies against tick-borne encephalitis virus, dengue virus, yellow fever virus and hepatitis c virus. this test may aid in counselling european travellers returning from regions where zikv is endemic.201627126052
structure of the thermally stable zika virus.zika virus (zikv), formerly a neglected pathogen, has recently been associated with microcephaly in fetuses, and with guillian-barré syndrome in adults. here we present the 3.7 å resolution cryo-electron microscopy structure of zikv, and show that the overall architecture of the virus is similar to that of other flaviviruses. sequence and structural comparisons of the zikv envelope (e) protein with other flaviviruses show that parts of the e protein closely resemble the neurovirulent west nile a ...201627093288
zika virus ns1 structure reveals diversity of electrostatic surfaces among flaviviruses.the association of zika virus (zikv) infections with microcephaly has resulted in an ongoing public-health emergency. here we report the crystal structure of a c-terminal fragment of zikv nonstructural protein 1 (ns1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis and immune evasion. comparison with west nile and dengue virus ns1 structures reveals conserved features but diverse electrostatic characteristics at host-interaction interfaces, thus possibly ...201627088990
mosquito vectors and the spread of cancer: an overlooked connection?mosquitoes (diptera: culicidae) represent a key threat for millions of humans and animals worldwide, vectoring important pathogens and parasites, including malaria, dengue, filariasis, and zika virus. besides mosquito-borne diseases, cancers figure among the leading causes of mortality worldwide. it is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades. notably, there are few contrasting evidences of the relationship between cancer and m ...201627053131
characterizing the zika virus genome - a bioinformatics study.the recent epidemic of zika virus infections in south and latin america have raised serious concern on its ramifications for the population in the americas and spread of the virus worldwide. the zika virus disease is a relatively new phenomenon for which sufficient and comprehensive data and investigative reports have not been available to date.201627032927
zika virus and the current outbreak: an overview.zika virus (zikv), a mosquito-borne flavivirus closely related to yellow fever virus and dengue virus, is currently causing a large outbreak in the americas. historically, zikv infection was considered a sporadic, relatively mild disease characterised by fever, maculopapular rash, conjunctivitis and often arthralgia. however, current observational studies suggest that zikv may cause more severe neurological sequelae such as guillain-barre syndrome, and birth defects, mainly microcephaly, in babi ...201627020989
guillain-barré syndrome outbreak associated with zika virus infection in french polynesia: a case-control study.between october, 2013, and april, 2014, french polynesia experienced the largest zika virus outbreak ever described at that time. during the same period, an increase in guillain-barré syndrome was reported, suggesting a possible association between zika virus and guillain-barré syndrome. we aimed to assess the role of zika virus and dengue virus infection in developing guillain-barré syndrome.201626948433
[experience of integrated traditional chinese and western medicine in first case of imported zika virus disease in china].zika virus disease is an acute infectious disease caused by zika virus transmitted through aedes mosquitoes. to explore the therapeutic effect of integrated traditional chinese and western medicine for zika virus disease, the treatment process of the first imported case in china was reviewed.201626911940
notes from the field: evidence of zika virus infection in brain and placental tissues from two congenitally infected newborns and two fetal losses--brazil, 2015.zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. zika virus was first reported in brazil in may 2015 (1). by february 9, 2016, local transmission of infection had been reported in 26 countries or territories in the americas.* infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with s ...201626890059
false positive dengue ns1 antigen test in a traveller with an acute zika virus infection imported into switzerland.we report the first case of an acute zika virus infection imported into switzerland by a traveller returning from canoa quebrada, ceará state, in the north-eastern part of brazil. due to a false positive dengue virus ns1 antigen test, igg antibody seroconversion and a suggestive clinical picture,an acute dengue fever was initially considered. however, because of lack of specific igm-antibodies, stationary igg antibody titre and a negative dengue virus pcr test result, a dengue virus infection wa ...201626859285
[zika virus: a review to clinicians].zika virus is a flavivirus related to dengue virus, yellow fever virus and west nile virus. it is considered an emerging arbovirus transmitted by mosquitos of the genus aedes. its first description took place in 1947 in the zika forest in uganda, isolated on rhesus monkey used as bait to study the yellow fever virus. sporadic cases have been detected in african countries and at the end of the 70's in indonesia. in 2007, epidemics were described in micronesia and other islands in the pacific ocea ...201626849762
possible association between zika virus infection and microcephaly - brazil, 2015.in early 2015, an outbreak of zika virus, a flavivirus transmitted by aedes mosquitoes, was identified in northeast brazil, an area where dengue virus was also circulating. by september, reports of an increase in the number of infants born with microcephaly in zika virus-affected areas began to emerge, and zika virus rna was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. the brazil ministry of health (moh) established a tas ...201626820244
zika virus infection in a traveller returning from the maldives, june 2015.we report a zika virus (zikv) infection in a patient with fever and rash after returning to finland from maldives, june 2015. the patient had dengue virus (denv) igg and igm antibodies but pan-flavivirus rt-pcr and subsequent sequencing showed presence of zikv rna in urine. recent association of zikv with microcephaly highlights the need for laboratory differentiation of zikv from denv infection and the circulation of zikv in areas outside its currently known distribution range.201626794427
zika fever imported from thailand to japan, and diagnosed by pcr in the urines.in july 2014, a japanese traveller returning from thailand was investigated for fever, headache, rash and conjunctivitis. zika virus rna was detected in his urine sample by real-time reverse transcription polymerase chain reaction. serological tests showed cross reactivity of igm against the dengue virus. zika fever could be misdiagnosed or missed and should be considered in febrile patients with a rash, especially those returning from thailand.201626782128
autophagy and viral diseases transmitted by aedes aegypti and aedes albopictus.despite a long battle that was started by oswaldo cruz more than a century ago, in 1903, brazil still struggles to fight aedes aegypti and aedes albopictus, the mosquito vectors of dengue virus (denv), chikungynya virus (chikv) and zika virus (zikv). dengue fever has been a serious public health problem in brazil for decades, with recurrent epidemic outbreaks occurring during summers. in 2015, until november, 1,534,932 possible cases were reported to the ministry of healthv. more recently, the l ...201626774331
zika virus infections imported to italy: clinical, immunological and virological findings, and public health implications.we report the first two cases of laboratory confirmed zika virus (zikv) infections imported into italy from french polynesia. both patients presented with low grade fever, malaise, conjunctivitis, myalgia, arthralgia, ankle oedema, and axillary and inguinal lymphadenopathy. one patient showed leukopenia with relative monocytosis and thrombocytopenia. the diagnosis was based on zikv seroconversion in both cases and on zikv rna detection in one patient from acute serum sample. sera from both patie ...201525600600
time required to initiate outbreak and pandemic observational research.observational research focused upon emerging infectious diseases such as ebola virus, middle east respiratory syndrome, and zika virus has been challenging to quickly initiate. we aimed to determine the duration of start-up procedures and barriers encountered for an observational study focused upon such infectious outbreaks.201728288355
design and use of mouse control dna for dna biomarker extraction and pcr detection from urine: application for transrenal mycobacterium tuberculosis dna detection.urine samples are increasingly used for diagnosing infections including escherichia coli, ebola virus, and zika virus. however, extraction and concentration of nucleic acid biomarkers from urine is necessary for many molecular detection strategies such as polymerase chain reaction (pcr). since urine samples typically have large volumes with dilute biomarker concentrations making them prone to false negatives, another impediment for urine-based diagnostics is the establishment of appropriate cont ...201728285168
planning for the unexpected: ebola virus, zika virus, what's next?since 2000 we have witnessed global pandemics and public health emergencies of international concern. this review details which viruses are likely to caused further outbreaks and looks at the strategies and tools available to uk medical professionals to mitigate the threat posed.201627937012
preparedness for zika virus disease - new york city, 2016.the rapid spread of zika virus across the world health organization's region of the americas has had a direct effect on the u.s. health care delivery system. hospitals in new york city (nyc) have been implementing prevention and response efforts consistent with cdc guidance. as of september 21, 2016, a total of 715 cases of laboratory-confirmed zika virus disease had been diagnosed in new york state among travelers who returned from affected areas, their sexual contacts, or infants infected in u ...201627787490
quarantine for zika virus? where is the science?in january 2016, the world health organization warned that zika virus is "spreading explosively" in the americas and that up to 4 million infections could be present worldwide within a year. soon thereafter, some politicians and authors publicly advocated for quarantine of travelers returning from regions where mosquitoes carrying zika virus are prevalent. the public health tool of quarantine can be used to prevent the spread of infection by restricting the movement of persons who have been expo ...201627032458
[emerging infectious agents].emergence of many emerging or re-emerging infectious diseases have occurred over the past decade, some of which are major public threat. sars, mers-cov, highly pathogenic avian influenza a(h5n1), ebola virus disease have raised concerns because of their virulence, their mortality, and/or their modality of transmission, or their impact on maternofoetal transmission (zika virus). the witness of these emergences have conducted health authorities to have policies and plans and to imagine new organiz ...201627644171
lujo viral hemorrhagic fever: considering diagnostic capacity and preparedness in the wake of recent ebola and zika virus outbreaks.lujo virus is a novel old world arenavirus identified in southern africa in 2008 as the cause of a viral hemorrhagic fever (vhf) characterized by nosocomial transmission with a high case fatality rate of 80% (4/5 cases). whereas this outbreak was limited, the unprecedented ebola virus disease outbreak in west africa, and recent zika virus disease epidemic in the americas, has brought into acute focus the need for preparedness to respond to rare but potentially highly pathogenic outbreaks of zoon ...201627593704
standard finishing categories for high-throughput sequencing of viral genomes.viral genome sequencing has become the cornerstone of almost all aspects of virology. in particular, high-throughput, next-generation viral genome sequencing has become an integral part of molecular epidemiological investigations into outbreaks of viral disease, such as the recent outbreaks of middle eastern respiratory syndrome, ebola virus disease and zika virus infection. multiple institutes have acquired the expertise and necessary infrastructure to perform such investigations, as evidenced ...201627217167
why zika virus infection has become a public health concern?prior to 2015, zika virus (zikv) outbreaks had occurred in areas of africa, southeast asia, and the pacific islands. although a causal relationship between zika infection during pregnancy and microcephaly is strongly suspected, such a connection has not yet been scientifically proven. in may 2015, the outbreak of zikv infection in brazil led to reports of syndrome and pregnant women giving birth to babies with birth defects and poor pregnancy outcomes; the pan american health organization (paho) ...201627052792
particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens.bioterrorism agents that can be easily transmitted with high mortality rates and cause debilitating diseases pose major threats to national security and public health. the recent ebola virus outbreak in west africa and ongoing zika virus outbreak in brazil, now spreading throughout latin america, are case examples of emerging infectious pathogens that have incited widespread fear and economic and social disruption on a global scale. prophylactic vaccines would provide effective countermeasures a ...201727038091
potential high-risk areas for zika virus transmission in the contiguous united states.to understand where transmission of zika virus has the highest likelihood to occur in the contiguous united states with regard to its transmission both sexually and via aedes aegypti mosquito bites.201728323468
two-stage isothermal enzymatic amplification for concurrent multiplex molecular detection.the wide array of pathogens responsible for infectious diseases makes it difficult to identify causative pathogens with single-plex tests. although multiplex pcr detects multiple targets, it is restricted to centralized laboratories, which delays test results or makes multiplexing unavailable, depriving healthcare providers of critical, real-time information.201728073898
easy and inexpensive molecular detection of dengue, chikungunya and zika viruses in febrile patients.dengue (denv), chikungunya (chikv) and zika (zikv) are arthropod-borne viruses (arboviruses) sharing a common vector, the mosquito aedes aegypti. at initial stages, patients infected with these viruses have similar clinical manifestations, however, the outcomes and clinical management of these diseases are different, for this reason early and accurate identification of the causative virus is necessary. this paper reports the development of a rapid and specific nested-pcr for detection of denv, c ...201627477452
report from the world health organization's third product development for vaccines advisory committee (pdvac) meeting, geneva, 8-10th june 2016.the third meeting of who's product development for vaccines advisory committee (pdvac) was held in june 2016, with a remit to revisit the pathogen areas for which significant progress has occurred since recommendations from the 2015 meeting, as well as to consider new advances in the development of vaccines against other pathogens. since the previous meeting, significant progress has been made with regulatory approvals of the first malaria and dengue vaccines, and the first phase iii trials of a ...201728262332
guillain-barré syndrome.the term guillain-barré syndrome (gbs), the most frequent cause of acute paralytic neuropathy, covers a number of recognisably distinct variants. the exact cause of gbs is unknown, but 50-70% of cases appear 1-2weeks after a respiratory or gastrointestinal infection, or another immune stimulus that induces an aberrant autoimmune response targeting peripheral nerves and their spinal roots. the interplay between the microbial and host factors that dictate whether and how the immune response shifts ...201727666816
inhibitory effect of flavonoids against ns2b-ns3 protease of zika virus and their structure activity relationship.to determine the inhibitory activities of flavonoids against ns2b-ns3 protease of zika virus (zikv ns2b-ns3(pro)) expressed in escherichia coli bl21 (de3) and their structure activity relationship.201727885509
zika, or the burden of uncertainty.in the first phases of an infectious outbreak, health authorities have to face the challenge of communicating uncertainty. just when the attention of the public is at the top, information about what is going on is usually still missing. this is the case of zika crisis in latin america, where an association with microcephaly in newborns and neurological complications have been described, but not yet confirmed. despite this, and even if the risk would be mainly limited to pregnant women, zika thre ...201626980631
keeping the zika virus out of the assisted reproductive technology laboratory.the zika virus (zikv) epidemic spreading through south and central america, as well as several u.s. territories has created worldwide concern as the linkage between zikv infection and microcephaly has been established. both travel associated and sexually transmitted cases have put couples who live in nonendemic areas at risk of falling victim to effects of zika. the presence of zikv within reproductive tissues may pose a significant threat to patients seeking fertility services and to safety of ...201627618295
paediatric virology: a rapidly increasing educational challenge.the '2nd workshop on paediatric virology', which took place on saturday the 8th of october 2016 in athens, greece, provided an overview on recent views and advances on paediatric virology. emphasis was given to hiv-1 management in greece, a country under continuous financial crisis, hepatitis b vaccination in africa, treatment options for hepatitis c virus in childhood, zika virus in pregnancy and infancy, the burden of influenza on childhood, hand-foot-mouth disease and myocarditis associated w ...201728352303
structure and function of the zika virus full-length ns5 protein.the recent outbreak of zika virus (zikv) has infected over 1 million people in over 30 countries. zikv replicates its rna genome using virally encoded replication proteins. nonstructural protein 5 (ns5) contains a methyltransferase for rna capping and a polymerase for viral rna synthesis. here we report the crystal structures of full-length ns5 and its polymerase domain at 3.0 å resolution. the ns5 structure has striking similarities to the ns5 protein of the related japanese encephalitis virus. ...201728345656
purification of zika virus rna-dependent rna polymerase and its use to identify small-molecule zika inhibitors.the viral rna-dependent rna polymerase (rdrp) enzymes of the flaviviridae family are essential for viral replication and are logically important targets for development of antiviral therapeutic agents. zika virus (zikv) is a rapidly re-emerging human pathogen for which no vaccine or antiviral agent is currently available.201728069884
identification of novel small molecule inhibitors against ns2b/ns3 serine protease from zika virus.zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as guillain-barré syndrome. the zika virus is now widespread in central and south america, and is anticipated to become an increasing risk in the southern united states. with continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the zika virus. the zik ...201728034741
the fda-approved drug sofosbuvir inhibits zika virus infection.the rapidly expanding zika virus (zikv) epidemic has affected thousands of individuals with severe cases causing guillain-barré syndrome, congenital malformations, and microcephaly. currently, there is no available vaccine or therapy to prevent or treat zikv infection. we evaluated whether sofosbuvir, an fda-approved nucleotide polymerase inhibitor for the distantly related hepatitis c virus, could have antiviral activity against zikv infection. cell culture studies established that sofosbuvir e ...201727902933
adenosine triphosphate analogs can efficiently inhibit the zika virus rna-dependent rna polymerase.we describe the expression and purification of an active recombinant zika virus rna-dependent rna polymerase (rdrp). next, we present the development and optimization of an in vitro assay to measure its activity. we then applied the assay to selected triphosphate analogs and discovered that 2'-c-methylated nucleosides exhibit strong inhibitory activity. surprisingly, also carbocyclic derivatives with the carbohydrate locked in a north-like conformation as well as a ribonucleotide with a south co ...201727902932
zika viral polymerase inhibition using anti-hcv drugs both in market and under clinical trials.in the last few months, a new zika virus (zikv) outbreak evolved in america. in accordance, world health organization (who) in february 2016 declared it as public health emergency of international concern (pheic). zikv infection was reported in more than 60 countries and the disease was spreading since 2007 but with little momentum. many antiviral drugs are available in market or in laboratories under clinical trials, could affect zikv infection. in silico docking study were performed on the zik ...201627604059
evolving rna virus pandemics: hiv, hcv, ebola, dengue, chikunguya, and now zika!the zika virus (zikv), a flavivirus related to yellow fever, dengue, and west nile, originated in the zika forest in uganda and was discovered in a rhesus monkey in 1947. the disease now has "explosive" pandemic potential, with outbreaks in africa, southeast asia, the pacific islands, and the americas. to date, the cdc has issued travel alerts for at least 30 countries and territories in latin america, the caribbean, polynesia, and cape verde in africa.201627028271
preventing transmission of zika virus in labor and delivery settings through implementation of standard precautions - united states, 2016.zika virus transmission was detected in the region of the americas (americas) in brazil in may 2015, and as of march 21, 2016, local mosquito-borne transmission of zika virus had been reported in 32 countries and territories in the americas, including puerto rico and the u.s. virgin islands.* most persons infected with zika virus have a mild illness or are asymptomatic. however, increasing evidence supports a link between zika virus infection during pregnancy and adverse pregnancy and birth outc ...201627010422
hsv-2 enhances zikv infection of the placenta and induces apoptosis in first-trimester trophoblast cells.zika virus (zikv) has gained public concern for its association with microcephaly in infants born to zikv-infected mothers. to reach the fetus the virus must overcome the defense mechanisms provided by trophoblast cells. additionally, in the first trimester, the integrity of the placenta is critical for fetal protection as damage to differentiating trophoblast can affect placental formation and function. we sought to investigate the effect of zikv infection on trophoblast cells and the factors t ...201627613665
production of immunogenic west nile virus-like particles using a herpes simplex virus 1 recombinant vector.west nile virus (wnv) is a flavivirus that swept rapidly across north america in 1999, declined in prevalence, and then resurged in 2012. to date, no vaccine is available to prevent infection in the human population. herpes simplex virus (hsv) replication-defective vaccine vectors induce a durable immunity characterized by strong antibody and cd8(+) t cell responses even in hsv-immune animals. in this study, a wnv protein expression cassette was optimized for virus-like particle (vlp) production ...201627336950
zika virus, hsv-2 and placenta. 201727868270
cutaneous manifestations of systemic viral diseases in neonates: an update.dermatologic findings may be the first signs of a neonatal viral infection. this review provides an update of the diagnostic features and therapies for selected viral illnesses [herpes simplex virus (hsv), varicella zoster virus, enterovirus, and zika virus] that present with cutaneous manifestations in the neonate.201728134705
zika virus infects early- and midgestation human maternal decidual tissues, inducing distinct innate tissue responses in the maternal-fetal interface.zika virus (zikv) has emerged as a cause of congenital brain anomalies and a range of placenta-related abnormalities, highlighting the need to unveil the modes of maternal-fetal transmission. the most likely route of vertical zikv transmission is via the placenta. the earliest events of zikv transmission in the maternal decidua, representing the maternal uterine aspect of the chimeric placenta, have remained unexplored. here, we show that zikv replicates in first-trimester human maternal-decidua ...201727974560
minimal immune determinants connect zika virus, human cytomegalovirus, and toxoplasma gondii to microcephaly-related human proteins.aiming at the molecular definition of the relationship(s) between prenatal infections and fetal microcephaly and using pentapeptides as minimal immune determinants, we analyzed the peptide matching between proteins from infectious agents involved in microcephalic syndromes (namely zika virus, human cytomegalovirus, and toxoplasma gondii) and human proteins that, when altered, have been specifically associated with microcephaly. we report that an unexpected high number of epitopic pentapeptides ( ...201727878897
case reports and their importance in medical literature.it is important to appreciate how case reports have paved the way for modern research. they are still largely considered the first line of evidence. indeed global endemics such as hiv and zika virus have been traced back to initial case reports. strictly speaking; case reports are anecdotes - a factual story telling about nature's own experiment. case reports can be characterized by two huge advantages, their ability to present novel, rare cases in a manner that can lead to the expansion in rese ...201728303999
policy making for vaccine use as a driver of vaccine innovation and development in the developed world.in the past 200years, vaccines have had unmistakable impacts on public health including declines in morbidity and mortality, most markedly in economically-developed countries. highly engineered vaccines including vaccines for conditions other than infectious diseases are expected to dominate future vaccine development. we examine immunization vaccine policy as a driver of vaccine innovation and development. the pathways to recommendation for use of licensed vaccines in the us, uk, canada and aus ...201728253995
infectious zika virus in vaginal secretions from an hiv-infected woman, france, august 2016.a woman with controlled hiv infection developed in late august 2016 a pruritic rash with fever and conjunctival hyperaemia after a trip to the french caribbean islands. on day 3 after symptom onset, zika virus rna was detected in plasma, urine and vaginal samples with respective viral loads of 3.8, 6.1 and 5.3 log copies/ml. notably, we demonstrated the presence of infectious zika virus particles in the vaginal samples by isolation in cell culture.201728128730
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