| n-methylisatin-beta-thiosemicarbazone derivative (sch 16) is an inhibitor of japanese encephalitis virus infection in vitro and in vivo. | during the early and mid part of 20th century, several reports described the therapeutic effects of n-methylisatin-beta-thiosemicarbazone (mibt) against pox viruses, maloney leukemia viruses and recently against hiv. however, their ability to inhibit flavivirus replication has not been investigated. hence the present study was designed to evaluate the antiviral activity of 14 mibt derivatives against flaviviruses that are prevalent in india such as japanese encephalitis virus (jev), dengue-2 (de ... | 2008 | 18498627 |
| standardized quantitative rt-pcr assays for quantitation of yellow fever and chimeric yellow fever-dengue vaccines. | yellow fever-dengue chimeras (cyds) are being developed currently as live tetravalent dengue vaccine candidates. specific quantitative assays are needed to evaluate the viral load of each serotype in vaccine batches and biological samples. a quantitative real-time rt-pcr (qrt-pcr) system was developed comprising five one-step qrt-pcrs targeting the e/ns1 junction of each chimera, or the ns5 gene in the yellow fever backbone. each assay was standardized using in vitro transcribed rna qualified ac ... | 2008 | 18501437 |
| limited replication of yellow fever 17dd and 17d-dengue recombinant viruses in rhesus monkeys. | for the development of safe live attenuated flavivirus vaccines one of the main properties to be established is viral replication. we have used real-time reverse transcriptase-polymerase chain reaction and virus titration by plaque assay to determine the replication of yellow fever 17dd virus (yfv 17dd) and recombinant yellow fever 17d viruses expressing envelope proteins of dengue virus serotypes 2 and 4 (17d-denv-2 and 17d-denv-4). serum samples from rhesus monkeys inoculated with yfv 17dd and ... | 2008 | 18506257 |
| dysregulation of tlr3 impairs the innate immune response to west nile virus in the elderly. | west nile virus (wnv), a mosquito-borne flavivirus, has recently emerged in north america, and the elderly are particularly susceptible to severe neurological disease and death from infection with this virus. we have investigated the innate immune response of primary human macrophages to wnv in vitro and have found significant differences between the responsiveness of macrophages derived from younger donors and that from older donors. binding of the glycosylated wnv envelope protein to the c-typ ... | 2008 | 18508883 |
| tick-borne encephalitis. | we review the epidemiological and clinical characteristics of tick-borne encephalitis, and summarise biological and virological aspects that are important for understanding the life-cycle and transmission of the virus. tick-borne encephalitis virus is a flavivirus that is transmitted by ixodes spp ticks in a vast area from western europe to the eastern coast of japan. tick-borne encephalitis causes acute meningoencephalitis with or without myelitis. morbidity is age dependent, and is highest in ... | 2008 | 18514730 |
| communicable diseases network australia national arbovirus and malaria advisory committee annual report, 2006-07. | this report describes the epidemiology of mosquito-borne disease in australia for the mosquito-borne disease season 1 july 2006 to 30 june 2007, which was moderately low compared to previous seasons. ross river virus (rrv) infections (55%), barmah forest virus (bfv) infections (29%) and overseas acquired malaria (11%) were the most common mosquito-borne diseases reported in 2006-07. the number, proportion and rate of national bfv notifications were the second highest on record since 1998-99. the ... | 2008 | 18522303 |
| analysis of the effects of alterations in the tick-borne encephalitis virus 3'-noncoding region on translation and rna replication using reporter replicons. | the 3'-noncoding region (3'-ncr) of the flavivirus genome includes a variable region that tolerates the insertion of heterologous genetic information. natural isolates of tick-borne encephalitis virus (tbev) have particularly long variable regions, which, for some strains, include an internal poly(a) tract. we constructed luciferase reporter replicons of tbev to analyze the impact of various manipulations of the 3'-ncr on viral rna translation and replication. the choice of the reporter gene, it ... | 2008 | 18533218 |
| extrinsic incubation periods for horizontal and vertical transmission of west nile virus by culex pipiens pipiens (diptera: culicidae). | culex pipiens pipiens l. (diptera: culicidae), infected per os from a membrane feeder, transmitted west nile virus (family flaviviridae, genus flavivirus, wnv) at 26 degrees c horizontally during feeding to hamsters and suckling mice and vertically to f1 progeny during egg deposition. horizontal transmission rates increased with extrinsic incubation, with 75-100% of the females transmitting on days 16 through 25 postinfection (pi). no females deposited eggs infected with wnv after the first bloo ... | 2008 | 18533438 |
| vector competence of aedes vexans (diptera: culicidae) for west nile virus and potential as an enzootic vector. | vector competence of aedes vexans (meigen) and culex pipiens pipiens l. (diptera: culicidae) for west nile virus (family flaviviridae, genus flavivirus, wnv) was compared. infection rates of both species were similar 14 d after feeding on chickens, with wnv titers ranging from 10(4.2) to 10(8.7) plaque-forming units (pfu)/ml. median infectious doses and 95% confidence intervals (ci) were 10(6.0(5.8, 63)) and 10(5.7(5.4, 5.9)) pfu for ae. vexans and cx. p. pipiens, respectively. wnv transmission ... | 2008 | 18533439 |
| using hydrologic conditions to forecast the risk of focal and epidemic arboviral transmission in peninsular florida. | the accurate forecasting and tracking of arboviral transmission is becoming increasingly critical for the early recognition and management of arboviral epidemics. meteorological factors, especially rainfall and temperature, drive arboviral epidemics, but monitoring rainfall and temperature alone is not predictive of increased levels of vector-borne disease transmission. in florida, model simulations of water table depth (wtd) provide a measure of drought, and they have been shown to provide an a ... | 2008 | 18533440 |
| arbovirus transmission by culex nigripalpus in florida, 2005. | understanding the transmission patterns of west nile and st. louis encephalitis viruses (family flaviviridae, genus flavivirus, wnv and slev) could result in an increased ability to predict transmission risk to humans. to examine transmission patterns between vector and host, we trapped mosquitoes in three florida counties from june to november 2005 by using chicken-baited lard can mosquito traps. these traps were used to monitor for presence of wnv and slev in mosquitoes and subsequent transmis ... | 2008 | 18533444 |
| persistent west nile virus transmission and the apparent displacement st. louis encephalitis virus in southeastern california, 2003-2006. | west nile virus (family flaviviridae, genus flavivirus, wnv) invaded the colorado desert biome of southern california during summer 2003 and seemed to displace previously endemic st. louis encephalitis virus (family flaviviridae, genus flavivirus, slev, an antigenically similar flavivirus in the japanese encephalitis virus serocomplex). western equine encephalomyelitis virus (family togaviridae, genus alphavirus, weev), an antigenically distinct alphavirus, was detected during 2005 and 2006, ind ... | 2008 | 18533445 |
| failure of japanese encephalitis vaccine and infection in inducing neutralizing antibodies against west nile virus, people's republic of china. | we examined whether live attenuated japanese encephalitis (je) vaccine is effective in preventing west nile virus (wnv) infection in the people's republic of china. three groups were recruited into the study: patients with japanese encephalitis (je), healthy controls vaccinated with live attenuated 2 sa14-14-vaccine against je virus (jev), and unvaccinated healthy controls. serum samples were collected and screened for igg antibodies against jev by an indirect immunofluorescence assay. positive ... | 2008 | 18541783 |
| japanese encephalitis in a finnish traveler on a two-week holiday in thailand. | japanese encephalitis (je) virus is a mosquito-borne flavivirus, and one of the leading causes of epidemic encephalitis in southeast asia. reports of symptomatic jev encephalitis in tourists have been rare. we describe a case of symptomatic je transmitted in 2004 during a short two-week trip to common tourist attractions in thailand. | 2008 | 18556242 |
| efficient dengue virus (denv) infection of human muscle satellite cells upregulates type i interferon response genes and differentially modulates mhc i expression on bystander and denv-infected cells. | dengue virus (denv) is a mosquito-borne flavivirus that causes an acute febrile disease in humans, characterized by musculoskeletal pain, headache, rash and leukopenia. the cause of myalgia during denv infection is still unknown. to determine whether denv can infect primary muscle cells, human muscle satellite cells were exposed to denv in vitro. the results demonstrated for the first time high-efficiency infection and replication of denv in human primary muscle satellite cells. changes in globa ... | 2008 | 18559930 |
| use of synthetic peptides to represent surface-exposed epitopes defined by neutralizing dengue complex- and flavivirus group-reactive monoclonal antibodies on the native dengue type-2 virus envelope glycoprotein. | the reactions of neutralizing monoclonal antibodies (mabs) that defined dengue virus (denv) complex, flavivirus subgroup or group neutralizing epitopes were tested against synthetic peptide sequences from domains i, ii and iii of the envelope (e) glycoproteins of different denv-2 genotypes/strains. the denv complex-reactive mab identified the surface-exposed 304-gkfkv/ivkeia-313 peptides and the denv complex-conserved 393-kkgssigq/km-401 peptides in domain iii, which were located adjacently in t ... | 2008 | 18559931 |
| characterization of mosquito-adapted west nile virus. | west nile virus (wnv), a mosquito-borne flavivirus, has significantly expanded its geographical and host range since its 1999 introduction into north america. the underlying mechanisms of evolution of wnv and other arboviruses are still poorly understood. studies evaluating virus adaptation and fitness in relevant in vivo systems are largely lacking. in order to evaluate the capacity for host-specific adaptation and the genetic correlates of adaptation in vivo, this study measured phenotypic and ... | 2008 | 18559933 |
| west nile virus nonstructural protein 1 inhibits tlr3 signal transduction. | the innate immune response is the first line of defense against foreign pathogens. the recognition of virus-associated molecular patterns, including double- and single-stranded rna, by pattern recognition receptors initiates a cascade of signaling reactions. these result in the transcriptional upregulation and secretion of proinflammatory cytokines that induce an antiviral state. many viruses have evolved mechanisms to antagonize these responses in order to help them establish a productive infec ... | 2008 | 18562533 |
| changing the protease specificity for activation of a flavivirus, tick-borne encephalitis virus. | the infectivity of flavivirus particles depends on a maturation process that is triggered by the proteolytic cleavage of the precursor of the m protein (prm). this activation cleavage is naturally performed by ubiquitous cellular proteases of the furin family, which typically recognize the multibasic sequence motif r-x-r/k-r. previously, we demonstrated that a tick-borne encephalitis virus (tbev) mutant with an altered cleavage motif, r-x-r, produced immature, noninfectious particles that could ... | 2008 | 18562534 |
| association of hepatitis c virus replication complexes with microtubules and actin filaments is dependent on the interaction of ns3 and ns5a. | the hepatitis c virus (hcv) rna replication complex (rc), which is composed of viral nonstructural (ns) proteins and host cellular proteins, replicates the viral rna genome in association with intracellular membranes. two viral ns proteins, ns3 and ns5a, are essential elements of the rc. here, by using immunoprecipitation and fluorescence resonance energy transfer assays, we demonstrated that ns3 and ns5a interact with tubulin and actin. furthermore, immunofluorescence microscopy and electron mi ... | 2008 | 18562541 |
| dengue vaccines for travelers. | dengue is an arthropod-borne infection caused by a flavivirus and spread by the aedes mosquitoes. many of the countries where dengue is endemic are popular tourist destinations and the disease is an increasingly important problem encountered by international travelers. personal protection against the day-feeding dengue vectors is problematic, indicating the urgent need for a dengue vaccine. this review discusses the challenges of vaccine development, current vaccine strategies and the prospects ... | 2008 | 18564012 |
| flavivirus methyltransferase: a novel antiviral target. | many flaviviruses are significant human pathogens. no effective antiviral therapy is currently available for treatment of flavivirus infections. development of antiviral treatment against these viruses is urgently needed. the flavivirus methyltransferase (mtase) responsible for n-7 and 2'-o methylation of the viral rna cap has recently been mapped to the n-terminal region of nonstructural protein 5. structural and functional studies suggest that the mtase represents a novel antiviral target. her ... | 2008 | 18571739 |
| novel binding between pre-membrane protein and vacuolar atpase is required for efficient dengue virus secretion. | flavivirus pre-membrane (prm) protein is important for proper folding and secretion of envelope (e) protein. however, other non-structural functions of prm protein in the context of virus life-cycle are poorly known. in this study, we aimed to elucidate if dengue virus (dv) prm protein interacts with host proteins and contributes to viral pathogenesis by screening human liver cdna yeast-two-hybrid library. our study identified vacuolar atpase (v-atpase) as a novel interacting partner of dv prm p ... | 2008 | 18573235 |
| safety of flavivirus chimeric vaccines: answer to ishikawa et al. [vaccine 26 (22) (2008) 2772-2781]. | | 2008 | 18573573 |
| [genotyping of japanese encephalitis viruses isolated in yunnan]. | explore the genotype of the epidemic japanese encephalitis virus (jev) in yunnan province from molecular level and to understand the molecular differences of the virus isolated from yunnan at different time, locality and host. | 2008 | 18574523 |
| is quantum mechanics necessary for predicting binding free energy? | to take into account polarization effects, the linear interaction energy model with continuum electrostatic solvation (liece) is supplemented by the linear-scaling semiempirical quantum mechanical calculation of the intermolecular electrostatic energy (qmliece). qmliece and liece are compared on three enzymes belonging to different classes: the west nile virus ns3 serine protease (wnv pr), the aspartic protease of the human immunodeficiency virus (hiv-1 pr), and the human cyclin-dependent kinase ... | 2008 | 18578469 |
| closing the door on flaviviruses: entry as a target for antiviral drug design. | with the emergence and rapid spread of west nile virus in the united states since 1999, and the 50-100 million infections per year caused by dengue virus globally, the threat of flaviviruses as re-emerging human pathogens has become a reality. to support the efforts that are currently being pursued to develop effective vaccines against these viruses, researchers are also actively pursuing the development of small molecule compounds that target various aspects of the virus life cycle. recent adva ... | 2008 | 18585795 |
| preliminary evaluation of exotic tick species and exotic pathogens imported on migratory birds into the british isles. | field studies were carried out to determine whether ticks are being imported into the british isles on migratory birds. during spring and autumn migration 2004, ticks were collected from ringed birds at 11 bird observatories and 3 inland riparia riparia colonies. a total of 38 ticks of 4 species (ixodes ricinus, i. frontalis, i. lividus, i. arboricola) were collected from 12 species of bird. ticks were tested for viruses in the flavivirus and nairovirus genera, with no positives found. this data ... | 2008 | 18585865 |
| interferon antagonist function of japanese encephalitis virus ns4a and its interaction with dead-box rna helicase ddx42. | the interferon (ifn) antagonists of japanese encephalitis virus (jev) proteins contribute to the je pathogenesis. most flavivirus non-structural (ns) proteins correlate with virus-induced inflammation and immune escape. ns4a proteins of west nile virus and dengue type 2 virus have been demonstrated to inhibit ifn signaling. in this study, jev ns4a without the c-terminal 2k domain has been demonstrated to partially block activation of an ifn-stimulated response element (isre)-based cis-reporter b ... | 2008 | 18588927 |
| [isolation of influenza virus a (orthomyxoviridae, influenza a virus), dhori virus (orthomyxoviridae, thogotovirus), and newcastle's disease virus (paromyxoviridae, avulavirus) on the malyi zhemchuzhnyi island in the north-western area of the caspian sea]. | the paper presents the results of the 2003 and 2006 environmental virological monitoring surveys on the malyi zhemchuzhnyi island where a large breeding colony of sea gull (laridae) is located. in the past several years, expansion of cormorants (phalacrocorax carbo) has enhanced the intensity of populational interactions. the investigators isolated 13 strains of influenza a virus (orthomyxoviridae, influenza a virus) subtype h13n1 (from sea gulls (n = 4), cormorants (n = 9) 1 strain of dhori vir ... | 2008 | 18590134 |
| ligation-mediated amplification for effective rapid determination of viral rna sequences (rdv). | emerging infectious diseases pose a significant risk to public health. methods for rapid detection of pathogens are needed to effectively treat these diseases. recently, we developed new methods for the rapid determination of viral rna sequences, rdv ver1.0 and ver2.0. we demonstrated that these methods were able to simultaneously detect cdna fragments of many different viruses without using sequence specific primers. however, some species of viruses, including the yokose virus (yokv), a flavivi ... | 2008 | 18595773 |
| viral membrane fusion. | infection by viruses having lipid-bilayer envelopes proceeds through fusion of the viral membrane with a membrane of the target cell. viral 'fusion proteins' facilitate this process. they vary greatly in structure, but all seem to have a common mechanism of action, in which a ligand-triggered, large-scale conformational change in the fusion protein is coupled to apposition and merger of the two bilayers. we describe three examples--the influenza virus hemagglutinin, the flavivirus e protein and ... | 2008 | 18596815 |
| "guidelines for the clinical evaluation of dengue vaccines in endemic areas": summary of a world health organization technical consultation. | there is a pressing need for guidelines focused on the clinical evaluation of dengue vaccines in exposed populations, because phase 1 and 2 clinical trials of dengue vaccines have begun, and phase 3 field trials may be warranted soon. in response to this need, the who initiative for vaccine research (ivr) has conducted a series of expert consultations resulting in guidelines published as a who; 2008[report no.: who/ivb/08.12]. this document, directed toward national regulatory authorities (nras) ... | 2008 | 18597906 |
| present perspectives on flaviviral chemotherapy. | flaviviruses are a group of arboviruses under the family of flaviviridae. flaviviruses are global pathogens, some of which cause neurotrophic disorders from mild febrile illness to lethal encephalitis while others cause severe hemorrhagic fever. these viruses are endemic to many parts of the world and periodic outbreaks take thousands of lives. with globalization of the world accompanied by gradual shift in global climate, the viruses are emerging in newer areas and we are in a point of exigency ... | 2008 | 18598919 |
| japanese encephalitis viral infection remains common in japan. | | 2008 | 18600187 |
| identification and biochemical characterization of small-molecule inhibitors of west nile virus serine protease by a high-throughput screen. | west nile virus and dengue virus are mosquito-borne flaviviruses that cause a large number of human infections each year. no vaccines or chemotherapeutics are currently available. these viruses encode a serine protease that is essential for polyprotein processing, a required step in the viral replication cycle. in this study, a high-throughput screening assay for the west nile virus protease was employed to screen approximately 32,000 small-molecule compounds for identification of inhibitors. le ... | 2008 | 18606844 |
| synthesis and evaluation of n-substituted acridones as antiviral agents against haemorrhagic fever viruses. | in the present study, a series of n-substituted acridone derivatives was synthesized and evaluated against two haemorrhagic fever viruses (hfv). | 2008 | 18610557 |
| design, synthesis, and biological evaluation of antiviral agents targeting flavivirus envelope proteins. | flavivirus envelope proteins (e proteins) have been shown to play a pivotal role in virus assembly, morphogenesis, and infection of host cells. inhibition of flavivirus infection of a host cell by means of a small molecule envelope protein antagonist is an attractive strategy for the development of antiviral agents. virtual screening of the nci chemical database using the dengue virus envelope protein structure revealed several hypothetical hit compounds. bioassay results identified a class of t ... | 2008 | 18610998 |
| the flavivirus polymerase as a target for drug discovery. | flaviviruses are emerging pathogens of increasingly important public health concern in the world. for most flaviviruses such as dengue virus (denv) and west nile virus (wnv) neither vaccine nor antiviral treatment is available. the viral rna-dependent rna polymerase (rdrp) non-structural protein 5 (ns5) has no equivalent in the host cell and is essential for viral replication. here, we give an overview of the current knowledge regarding flavivirus rdrp function and structure as it represents an ... | 2008 | 18611413 |
| specific genetic markers for detecting subtypes of dengue virus serotype-2 in isolates from the states of oaxaca and veracruz, mexico. | dengue (den) is an infectious disease caused by the den virus (denv), which belongs to the flavivirus genus in the family flaviviridae. it has a (+) sense rna genome and is mainly transmitted to humans by the vector mosquito aedes aegypti. dengue fever (df) and dengue hemorrhagic fever (dhf) are caused by one of four closely related virus serotypes (denv-1, denv-2, denv-3 and denv-4). epidemiological and evolutionary studies have indicated that host and viral factors are involved in determining ... | 2008 | 18625078 |
| tumor necrosis factor alpha protects against lethal west nile virus infection by promoting trafficking of mononuclear leukocytes into the central nervous system. | west nile virus (wnv) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans, especially in immunocompromised individuals. previous studies have shown essential protective roles for antiviral cytokines (e.g., alpha interferon [ifn-alpha] and ifn-gamma) against wnv in mice. however, studies using cell culture offer conflicting answers regarding whether tumor necrosis factor alpha (tnf-alpha) has an anti-wnv function. to test the biological sig ... | 2008 | 18632856 |
| differential cholesterol binding by class ii fusion proteins determines membrane fusion properties. | the class ii fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving the fusion of the virus membrane with that of the cell. these fusion proteins are triggered by low ph, and their structures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformations. here we have compared cholesterol interactions during membrane fusion by these two groups of viruses. using cholesterol-depleted insect cells, we showed that fusion and infection ... | 2008 | 18632857 |
| japanese encephalitis virus infection activates caspase-8 and -9 in a fadd-independent and mitochondrion-dependent manner. | japanese encephalitis virus (jev), a mosquito-borne flavivirus, replicates primarily at the endoplasmic reticulum and thereby triggers apoptosis of infected cells. this study investigated the hierarchical activation of the caspase network induced by jev infection. it was found that jev activated the initiators caspase-8 and -9, as well as effector caspase-3, in infected baby hamster kidney and mouse neuroblastoma (n18) cells. in neuronal n18 cells, jev infection triggered cytochrome c release fr ... | 2008 | 18632964 |
| climbing the steps of viral atomic force microscopy: visualization of dengue virus particles. | in recent years, the application of atomic force microscopy (afm) to biological systems has highlighted the potential of this technology. afm provides insights into studies of biological structures and interactions and can also identify and characterize a large panel of pathogens, including viruses. the flaviviridae family contains a number of viruses that are important human and animal pathogens. among them, dengue virus causes epidemics with fatal outcomes mainly in the tropics. in this study, ... | 2008 | 18638201 |
| structural and functional characterization of nonstructural protein 2 for its role in hepatitis c virus assembly. | the hepatitis c virus (hcv) is a flavivirus replicating in the cytoplasm of infected cells. the hcv genome is a single-stranded rna encoding a polyprotein that is cleaved by cellular and viral proteases into 10 different products. while the structural proteins core protein, envelope protein 1 (e1) and e2 build up the virus particle, most nonstructural (ns) proteins are required for rna replication. one of the least studied proteins is ns2, which is composed of a c-terminal cytosolic protease dom ... | 2008 | 18644781 |
| serological evidence of usutu virus occurrence in north-eastern italy. | in the recent years, usutu virus (usuv), a flavivirus of the japanese encephalitis virus complex, has been reported in central europe. as part of a systematic surveillance programme to monitor possible entrance and/or circulation of vector-borne viruses, since 2001, sentinel-chicken flocks were placed throughout the italian territory nearby areas considered at risk of virus introduction. they have been periodically checked for the presence of antibodies against flaviviruses by indirect elisa, pl ... | 2008 | 18667029 |
| spatial and temporal organization of tick-borne encephalitis flavivirus replicated rna in living cells. | flaviviruses are positive rna viruses that assemble the replication complex in the cytoplasm of the infected cells. in order to get a dynamic view of the formation and distribution of flavivirus genomes in living cells we engineered a tick-borne encephalitis virus (tbev) replicon with an array of binding sites for the phage ms2 core protein. the modified tbev replicons were competent for rna replication and allowed the visualization of replicated genomic rna that accumulated in cytoplasmic struc ... | 2008 | 18667221 |
| a complex rna motif defined by three discontinuous 5-nucleotide-long strands is essential for flavivirus rna replication. | tertiary or higher-order rna motifs that regulate replication of positive-strand rna viruses are as yet poorly understood. using japanese encephalitis virus (jev), we now show that a key element in jev rna replication is a complex rna motif that includes a string of three discontinuous complementary sequences (tdcs). the tdcs consists of three 5-nt-long strands, the left (l) strand upstream of the translation initiator aug adjacent to the 5'-end of the genome, and the middle (m) and right (r) st ... | 2008 | 18669441 |
| phase 2 clinical trial of three formulations of tetravalent live-attenuated dengue vaccine in flavivirus-naïve adults. | sixteen dose formulations of our live-attenuated tetravalent dengue virus vaccines (tdv) were previously evaluated for safety and immunogenicity. two of the sixteen candidate tdv formulations (formulations 13 and 14) were selected for further evaluation. a new tdv formulation, formulation 17, using a higher primary dog kidney (pdk) cell passage dengue-1 virus (denv-1) and a lower pdk cell passage denv-4, was developed to optimize the neutralizing antibody response. all three formulations consist ... | 2009 | 18670195 |
| towards the design of antiviral inhibitors against flaviviruses: the case for the multifunctional ns3 protein from dengue virus as a target. | new treatments are urgently needed to combat the increasing number of dengue fever cases in endemic countries as well as amongst a large number of travellers from non-endemic countries. of the 10 virus encoded proteins, ns3 (non-structural 3) and ns5 carry out all the enzymatic activities needed for polyprotein processing and genome replication, and are considered to be amenable to antiviral inhibition by analogy with successes for similar targets in human immunodeficiency virus and hepatitis c ... | 2008 | 18674567 |
| one-step rt-pcr for detection of zika virus. | zika virus (zikv) is an emerging mosquito-borne flavivirus circulating in asia and africa. human infection induces an influenza-like syndrome that is associated with retro-orbital pain, oedema, lymphadenopathy, or diarrhea. diagnosis of zika fever requires virus isolation and serology, which are time consuming or cross-reactive. | 2008 | 18674965 |
| divergent picornavirus ires elements. | internal ribosome entry site (ires) elements were first identified about 20 years ago within the 5' untranslated region of picornavirus rnas. they direct a cap-independent mechanism of translation initiation on the viral rna. within the picornavirus family it is now known that there are four classes of ires element which vary in size (450-270 nt), they also have different, complex, secondary structures and distinct requirements for cellular proteins to allow them to function. this review describ ... | 2009 | 18675861 |
| the capsid-coding region hairpin element (chp) is a critical determinant of dengue virus and west nile virus rna synthesis. | dengue virus (denv) and west nile virus (wnv) are members of the flavivirus genus of positive-strand rna viruses. rna sequences and structures, primarily in the untranslated regions, have been shown to modulate flaviviral gene expression and genome replication. previously, we demonstrated that a structure in the denv coding region (chp) enhances translation start codon selection and is required for viral replication. here we further characterize the role of the chp in the denv life cycle. we dem ... | 2008 | 18676000 |
| genetic and serologic properties of zika virus associated with an epidemic, yap state, micronesia, 2007. | zika virus (zikv) is a mosquito-borne flavivirus first isolated in uganda from a sentinel monkey in 1947. mosquito and sentinel animal surveillance studies have demonstrated that zikv is endemic to africa and southeast asia, yet reported human cases are rare, with <10 cases reported in the literature. in june 2007, an epidemic of fever and rash associated with zikv was detected in yap state, federated states of micronesia. we report the genetic and serologic properties of the zikv associated wit ... | 2008 | 18680646 |
| prevalence of west nile virus neutralizing antibodies in wild birds from the camargue area, southern france. | the camargue area of southern france experienced the re-emergence of west nile virus (wnv) in the late summer of 2000 and 2004. immediately preceding the 2004 outbreak, samples were collected from 432 birds of 32 different species captured in mist nets and from 201 cattle egret (bubulcus ibis) nestlings sampled in their nests between 1 april and 12 june 2004. west nile virus neutralizing titers of >/=40 were detected in 4.8% (95% confidence limit, 2.9-7.5%) of the adult birds and in 1.6% (0.3-4. ... | 2008 | 18689669 |
| safety concerns with regard to live attenuated flavivirus vaccines. | | 2008 | 18694340 |
| genome cyclization as strategy for flavivirus rna replication. | long-range and local rna-rna contacts in viral rna genomes result in tertiary structures that modulate the function of enhancers, promoters, and silencers during translation, rna replication, and encapsidation. in the case of flaviviruses, the presence of inverted complementary sequences at the 5' and 3' ends of the genome mediate long-range rna interactions and rna cyclization. the circular conformation of flavivirus genomes was demonstrated to be essential for rna amplification. new ideas abou ... | 2009 | 18703097 |
| impact of aerial spraying of pyrethrin insecticide on culex pipiens and culex tarsalis (diptera: culicidae) abundance and west nile virus infection rates in an urban/suburban area of sacramento county, california. | in response to an epidemic amplification of west nile virus (family flaviviridae, genus flavivirus, wnv), the sacramento and yolo mosquito and vector control district (symvcd) sprayed ultralow-volume (ulv) formulations of pyrethrin insecticide (evergreen ec 60-6: 6% pyrethrin insecticide, 60% piperonylbutoxide; mgk, minneapolis, mn, applied as 0.003 kg/ha [0.0025 lb/acre] ) over 218 km2 in north sacramento and 243.5 km2 in south sacramento on three consecutive evenings in august 2005. we evaluat ... | 2008 | 18714879 |
| simulation of climate-change scenarios to explain usutu-virus dynamics in austria. | the emergence and spread of infectious diseases in mid-latitudes, so far mainly observed in the tropics, considerably increase under the current situation of climate change. a recent example is the usutu virus (usuv) outbreak in austria. usuv is closely related to the west nile virus in the u.s. and caused mass mortalities mainly of blackbirds (turdus merula). the usuv flavivirus persists in a natural transmission cycle between vectors (mosquitoes) and host reservoirs (birds) and leads - once en ... | 2009 | 18715663 |
| a duplex real-time reverse transcriptase polymerase chain reaction assay for the detection of st. louis encephalitis and eastern equine encephalitis viruses. | a duplex taqman real-time reverse transcriptase polymerase chain reaction (pcr) assay was developed for the detection of st. louis encephalitis virus (slev) and eastern equine encephalitis virus (eeev), for use in human and vector surveillance. the respective targets selected for the assay were the conserved ns5 and e1 genes of the 2 viruses. because of the insufficient number of ns5 sequences from slev strains in the genbank database, we determined the sequence of an approximately 1-kb region f ... | 2008 | 18715737 |
| differential modulation of prm cleavage, extracellular particle distribution, and virus infectivity by conserved residues at nonfurin consensus positions of the dengue virus pr-m junction. | in the generation of flavivirus particles, an internal cleavage of the envelope glycoprotein prm by furin is required for the acquisition of infectivity. unlike cleavage of the prm of other flaviviruses, cleavage of dengue virus prm is incomplete in many cell lines; the partial cleavage reflects the influence of residues at furin nonconsensus positions of the pr-m junction, as flaviviruses share basic residues at positions p1, p2, and p4, recognized by furin. in this study, viruses harboring the ... | 2008 | 18715923 |
| [future prospects in developing of dengue vaccines]. | dengue is a viral, febrile and acute disease that causes more morbility than any other infection for arbovirus. it becomes necessary to implement a safe and effective vaccine that will contribute to the eradication of this disease, especially in endemic areas with very low socio-economic conditions. the only option that exists at the present to control the transmission of the disease is through vector control. so far, there are no effective antiviral drugs for flavivirus such as dengue. candidat ... | 2008 | 18717261 |
| serum antibodies to west nile virus in naturally exposed and vaccinated horses. | a polyvalent elisa and plaque reduction neutralization tests (prnts) were used to measure serum antibodies to west nile virus (wnv) in horses naturally exposed to or vaccinated against this flavivirus in connecticut and new york state, usa. relying on a prnt as a 'gold standard', the main objective was to validate a modified elisa containing a recombinant wnv envelope protein antigen. it was also important to assess specificity by testing sera from horses that had other, undiagnosed illnesses. s ... | 2008 | 18719177 |
| expression of the dengue virus type 2 ns5 protein in a cd4(+) t cell line inhibits hiv replication. | human immunodeficiency virus (hiv) load is suppressed during dengue virus infection. the ns5a phosphoprotein of gb virus c (a related flavivirus) inhibits hiv replication in vitro. to determine whether the dengue virus ns5 protein inhibits hiv replication, cd4(+) t cell lines expressing this protein were generated. hiv replication in dengue virus ns5-expressing cells decreased by >90% compared with control cells (p < .01), and this was mediated in part by decreased hiv coreceptor (cxcr4) express ... | 2008 | 18721058 |
| innate resistance to flavivirus infections and the functions of 2'-5' oligoadenylate synthetases. | mouse susceptibility to experimental infections with flaviviruses is significantly influenced by a cluster of genes on chromosome 5 encoding a family of proteins with enzymatic properties, the 2'-5' oligoadenylate synthetases (oas). positional cloning of the locus in question has revealed that susceptibility of laboratory inbred strains to this class of virus is associated with a nonsense mutation in the gene encoding the oas1b isoform. analysis of the molecular structure of the cluster in diffe ... | 2008 | 18727488 |
| potent cationic inhibitors of west nile virus ns2b/ns3 protease with serum stability, cell permeability and antiviral activity. | west nile virus (wnv) has spread rapidly around the globe, efficiently crossing species from migrating birds into humans and other mammals. the viral protease ns2b-ns3 is important for wnv replication and recognizes dibasic substrate sequences common to other flaviviral proteases but different from most mammalian proteases. potent inhibitors of wnv protease with antiviral activity have been elusive to date. we report the smallest and most potent inhibitors known for this enzyme, cationic tripept ... | 2008 | 18729351 |
| [humoral immune response to structural and nonstructural proteins of tick-borne encephalitis virus in the natural history of the disease]. | a hundred and ninety-one patients who had fallen ill with tick-borne encephalitis (tbe) after bites by virus-carrying ticks were examined to reveal the characteristics of antibody production of the major classes of immunoglobulins (igm and igg) against structural protein e of the tbe virus and nonstructural protein ns1 of the tbe viral replicative complex in the natural history of an infectious process in different forms and variants of the disease. in the two-wave course of tbe, the infectious ... | 2008 | 18756813 |
| [serological monitoring of arbovirus infections in the estuary of the kuban river (the 2006-2007 data)]. | solid-phase enzyme immunoassay, neutralization test, and the hemagglutination-inhibition test were used to study the sera from human beings (152 samples), agricultural animals (n = 77), hares (n = 3), and wild birds (n = 69), collected in 2006-2007 in the kuban river estuary (temryuk district, krasnodar territory). there were specific antibodies against viruses of west nile (wh), tick-borne encephalitis (tbe) (flaviviridae, flavivirus), sindbis (togaviridae, alphavirus), the antigenic complex of ... | 2008 | 18756814 |
| phosphorylation of yellow fever virus ns5 alters methyltransferase activity. | serine/threonine phosphorylation of the nonstructural protein 5 (ns5) is conserved feature of flaviviruses, but the kinase(s) responsible and function(s) remain unknown. mass spectrometry was used to characterize phosphorylated residues of yellow fever virus (yfv) ns5 expressed in mammalian cells. multiple different phosphopeptides were detected. mutational and additional mass spectrometry data implicated serine 56 (s56), a conserved residue near the active site in the ns5 methyltransferase doma ... | 2008 | 18757072 |
| discovery of a hepatitis c target and its pharmacological inhibitors by microfluidic affinity analysis. | more effective therapies are urgently needed against hepatitis c virus (hcv), a major cause of viral hepatitis. we used in vitro protein expression and microfluidic affinity analysis to study rna binding by the hcv transmembrane protein ns4b, which plays an essential role in hcv rna replication. we show that hcv ns4b binds rna and that this binding is specific for the 3' terminus of the negative strand of the viral genome with a dissociation constant (kd) of approximately 3.4 nm. a high-throughp ... | 2008 | 18758449 |
| cell-mediated immunity induced by chimeric tetravalent dengue vaccine in naive or flavivirus-primed subjects. | three independent, phase 1 clinical trials were conducted in australia and in usa to assess the safety and immunogenicity of sanofi pasteur dengue vaccine candidates. in this context, dengue 1-4 and yellow fever 17d-204 (yf 17d)-specific cd4 and cd8 cellular responses induced by tetravalent chimeric dengue vaccines (cyd) were analyzed in flavivirus-naive or flavivirus-immune patients. tetravalent cyd vaccine did not trigger detectable changes in serum pro-inflammatory cytokines, whatever the vac ... | 2008 | 18762226 |
| [neglected arthropod-borne viral infections in the czech republic]. | central european encephalitis is the most common arthropod-borne virus disease in the czech republic, with the mean annual incidence of 6 cases per 100 000 population. however, seven less known arboviruses (flavivirus west nile, bunyavirus tahyna, bunyavirus batai, bunyavirus sedlec, bunyavirus lednice, orbivirus tribee, uukuvirus uukuniemi) also circulate in this country, of which west nile, tahyna, tribec and possibly batai have been reported to cause human disease. moreover, antibodies agains ... | 2008 | 18767374 |
| mutation of mapped tia-1/tiar binding sites in the 3' terminal stem-loop of west nile virus minus-strand rna in an infectious clone negatively affects genomic rna amplification. | previous data showed that the cellular proteins tia-1 and tiar bound specifically to the west nile virus 3' minus-strand stem-loop [wnv3'(-)sl] rna (37) and colocalized with flavivirus replication complexes in wnv- and dengue virus-infected cells (21). in the present study, the sites on the wnv3'(-)sl rna required for efficient in vitro t-cell intracellular antigen-related (tiar) and t-cell intracellular antigen-1 (tia-1) protein binding were mapped to short au sequences (uaauu) located in two i ... | 2008 | 18768985 |
| synthesis and study of 9-deazaguanosine derivatives as potential inhibitors of rna virus replication. | 9-deazaguanosine and the alpha and beta anomers of its 2'-c-methyl counter part, have been synthesized and evaluated against a broad range of rna viruses, including hepatitis c virus. | 2008 | 18776524 |
| structural insights into the mechanisms of antibody-mediated neutralization of flavivirus infection: implications for vaccine development. | flaviviruses are a group of small rna viruses that cause severe disease in humans worldwide and are the target of several vaccine development programs. a primary goal of these efforts is to elicit a protective humoral response directed against the envelope proteins arrayed on the surface of the flavivirus virion. advances in the structural biology of these viruses has catalyzed rapid progress toward understanding the complexity of the flavivirus immunogen and the molecular basis of antibody-medi ... | 2008 | 18779049 |
| early b-cell activation after west nile virus infection requires alpha/beta interferon but not antigen receptor signaling. | the b-cell response against west nile virus (wnv), an encephalitic flavivirus of global concern, is critical to controlling central nervous system dissemination and neurological sequelae, including death. here, using a well-characterized mouse model of wnv infection, we examine the factors that govern early b-cell activation. subcutaneous inoculation with a low dose of replicating wnv results in extensive b-cell activation in the draining lymph node (ln) within days of infection as judged by upr ... | 2008 | 18786989 |
| epizootology and experimental infection of yokose virus in bats. | to reveal whether bats serve as an amplifying host for yokose virus (yokv), we conducted a serological survey and experimentally infected fruit bats with yokv isolated from microbats in japan. yokv belongs to the entebbe bat virus group of vector unknown group within the genus flavivirus and family flaviviridae. to detect antibodies against yokv, we developed an enzyme-linked immunosorbent assay (elisa) using biotinylated anti-bat igg rabbit sera. serological surveillance was conducted with samp ... | 2010 | 18789527 |
| seroprevalence study on the diffusion of the west nile virus among blood donors, healthcare workers, jockeys, grooms and fowlers, veterinary surgeons and hunters in messina (italy). | west nile virus (wnv) is a mosquito-transmitted flavivirus widely distributed in africa, middle east, asia, southern europe and in 1999 was first identified in the united states as a cause of disease in new york city. it mainly circulates among birds, but can infect many species of mammals. epidemics can occur in rural as well as urban areas. | 2008 | 18792530 |
| molecular targets for flavivirus drug discovery. | flaviviruses are a major cause of infectious disease in humans. dengue virus causes an estimated 50 million cases of febrile illness each year, including an increasing number of cases of hemorrhagic fever. west nile virus, which recently spread from the mediterranean basin to the western hemisphere, now causes thousands of sporadic cases of encephalitis annually. despite the existence of licensed vaccines, yellow fever, japanese encephalitis and tick-borne encephalitis also claim many thousands ... | 2009 | 18796313 |
| association of dengue virus ns1 protein with lipid rafts. | during the replication of dengue virus, a viral non-structural glycoprotein, ns1, associates with the membrane on the cell surface and in the rna replication complex. ns1 lacks a transmembrane domain, and the mechanism by which it associates with the membrane remains unclear. this study aimed to investigate whether membrane-bound ns1 is present in lipid rafts in dengue virus-infected cells. double immunofluorescence staining of infected hek-293t cells revealed that ns1 localized with raft-associ ... | 2008 | 18796718 |
| terminal structures of west nile virus genomic rna and their interactions with viral ns5 protein. | genome cyclization is essential for flavivirus replication. we used rnases to probe the structures formed by the 5'-terminal 190 nucleotides and the 3'-terminal 111 nucleotides of the west nile virus (wnv) genomic rna. when analyzed individually, the two rnas adopt stem-loop structures as predicted by the thermodynamic-folding program. however, when mixed together, the two rnas form a duplex that is mediated through base-pairings of two sets of rna elements (5'cs/3'csi and 5'uar/3'uar). formatio ... | 2008 | 18799181 |
| temperature-dependent production of pseudoinfectious dengue reporter virus particles by complementation. | dengue virus (denv) is a mosquito-borne flavivirus responsible for 50 to 100 million human infections each year, highlighting the need for a safe and effective vaccine. in this study, we describe the production of pseudoinfectious denv reporter virus particles (rvps) using two different genetic complementation approaches, including the creation of cell lines that release reporter viruses in an inducible fashion. in contrast to studies with west nile virus (wnv), production of infectious denv rvp ... | 2008 | 18801552 |
| vero cells infected with vaccinia viruses expressing japanese encephalitis virus envelope protein induce polykaryocyte formation under neutral conditions. | flavivirus membranes fuse with cellular membranes by low ph-induced mechanisms. although japanese encephalitis virus (jev) has similar mechanisms, fusion induced under neutral conditions has been observed. we report herein polykaryocyte formation using vero cells infected with recombinant vaccinia viruses, vp829 expressing jev premembrane (prm) and envelope (e), or vp555 expressing prm, e, and the nonstructural proteins ns1 and ns2a. polykaryocytes were detected under ph 7.0 as early as 9 h afte ... | 2008 | 18806356 |
| identification of genetic determinants of a tick-borne flavivirus associated with host-specific adaptation and pathogenicity. | tick-borne flaviviruses are maintained in nature in an enzootic cycle involving a tick vector and a vertebrate host. thus, the virus replicates in two disparate hosts, each providing selective pressures that can influence virus replication and pathogenicity. to identify viral determinants associated with replication in the individual hosts, plaque purified langat virus (tp21pp) was adapted to growth in mouse or tick cell lines to generate two virus variants, mnbp20 and isep20, respectively. viru ... | 2008 | 18823640 |
| selection of cyclic peptide aptamers to hcv ires rna using mrna display. | the hepatitis c virus (hcv) is a positive strand rna flavivirus that is a major causative agent of serious liver disease, making new treatment modalities an urgent priority. because hcv translation initiation occurs by a mechanism that is fundamentally distinct from that of host mrnas, it is an attractive target for drug discovery. the translation of hcv mrna is initiated from an internal ribosomal entry site (ires), independent of cap and poly(a) recognition and bypassing eif4f complex formatio ... | 2008 | 18824687 |
| tick-borne encephalitis in mainland china. | tick-borne encephalitis (tbe) virus is one of the most important flavivirus infections of the central nervous system in europe and russia, with 12,000 estimated human cases per year. at present, epidemiology is extensively analyzed in many regions of europe and russia, with less activity in east and southeast asia. for china, surveillance on tbe is not institutionalized, and data are incomplete and not appropriately communicated. this review summarizes the current knowledge on tbe in china and s ... | 2008 | 18837668 |
| the structural immunology of antibody protection against west nile virus. | summary: recent investigations of the interaction between the west nile virus (wnv) envelope protein (e) and monoclonal antibodies (mabs) have elucidated fundamental insights into the molecular mechanisms of neutralization. structural studies have defined an epitope on the lateral ridge of domain iii (diii-lr) of the wnv e protein that is recognized by antibodies with the strongest neutralizing activity in vitro and in vivo. antibodies that bind this epitope are highly potent because they effici ... | 2008 | 18837784 |
| tick-borne flaviviruses: dissecting host immune responses and virus countermeasures. | the tick-borne encephalitis (tbe) serocomplex of viruses, genus flavivirus, includes a number of important human pathogens that cause serious neurological illnesses and hemorrhagic fevers. these viruses pose a significant public health problem due to high rates of morbidity and mortality, their emergence to new geographic areas, and the recent rise in the incidence of human infections. the most notable member of the tbe serocomplex is tick-borne encephalitis virus (tbev), a neurotropic flaviviru ... | 2009 | 18841330 |
| substrate inhibition kinetic model for west nile virus ns2b-ns3 protease. | west nile virus (wnv) has recently emerged in north america as a significant disease threat to humans and animals. unfortunately, no approved antiviral drugs exist to combat wnv or other members of the genus flavivirus in humans. the wnv ns2b-ns3 protease has been one of the primary targets for anti-wnv drug discovery and design since it is required for virus replication. as part of our efforts to develop effective wnv inhibitors, we reexamined the reaction kinetics of the ns2b-ns3 protease and ... | 2008 | 18855422 |
| metal ion-binding studies highlight important differences between flaviviral rna polymerases. | west nile virus (wnv) is a member of the flaviviridae family which includes a number of important human pathogens. the wnv ns5 protein harbors an rna-dependent rna polymerase activity which is required both for replication and transcription of the viral genome. to extend our studies on the role of metal ions in the activity of flaviviral polymerases, we have used fluorescence spectroscopy, circular dichroism, and a combination of chemical and thermal denaturation assays to monitor the consequenc ... | 2009 | 18930844 |
| the ph sensor for flavivirus membrane fusion. | viruses that infect cells by uptake through endosomes have generally evolved to "sense" the local ph as part of the mechanism by which they penetrate into the cytosol. even for the very well studied fusion proteins of enveloped viruses, identification of the specific ph sensor has been a challenge, one that has now been met successfully, for flaviviruses, by fritz et al. (fritz, r., k. stiasny, and f.x. heinz. 2008. j. cell biol. 183:353-361) in this issue. thorough mutational analysis of conser ... | 2008 | 18936246 |
| identification of specific histidines as ph sensors in flavivirus membrane fusion. | the flavivirus membrane fusion machinery, like that of many other enveloped viruses, is triggered by the acidic ph in endosomes after virus uptake by receptor-mediated endocytosis. it has been hypothesized that conserved histidines in the class ii fusion protein e of these viruses function as molecular switches and, by their protonation, control the fusion process. using the mutational analysis of recombinant subviral particles of tick-borne encephalitis virus, we provide direct experimental evi ... | 2008 | 18936253 |
| increased recognition of powassan encephalitis in the united states, 1999-2005. | powassan virus (powv) disease is a rare human disease caused by a tick-borne encephalitis group flavivirus maintained in a transmission cycle between ixodes cookei and other ixodid ticks and small and medium-sized mammals. during 1958-1998, only 27 powv disease cases (mostly powassan encephalitis) were reported from eastern canada and the northeastern united states (average, 0.7 cases per year). during 1999-2005, nine cases (described herein) of serologically confirmed powv disease were reported ... | 2008 | 18959500 |
| the hidden passenger of lucky bamboo: do imported aedes albopictus mosquitoes cause dengue virus transmission in the netherlands? | since 2005, aedes albopictus mosquitoes have been detected in companies in the netherlands that import ornamental plants from china. to assess the risks of dengue transmission, a study was carried out in 48 persons who are professionally exposed to these mosquitoes. no evidence for non-travel-related flavivirus infections was found. | 2009 | 18959501 |
| detection and monitoring of mosquito flaviviruses in spain between 2001 and 2005. | between the years 2001 and 2005, a total of 72,895 female mosquitoes were trapped during their season of abundance, and analyzed. they were sorted into 4,723 pools belonging to 20 culicidae species from the anopheles, aedes, ochlerotatus, culex, culiseta, coquillettidia, and uranotaenia genera. the aim was to detect arboviral rna directly from mosquito homogenates for the genera alphavirus, flavivirus, and phlebovirus. the study formed part of general arbovirus transmission research in four of t ... | 2009 | 18959502 |
| mechanism of ns2b-mediated activation of ns3pro in dengue virus: molecular dynamics simulations and bioassays. | the ns2b cofactor is critical for proteolytic activation of the flavivirus ns3 protease. to elucidate the mechanism involved in ns2b-mediated activation of ns3 protease, molecular dynamic simulation, principal component analysis, molecular docking, mutagenesis, and bioassay studies were carried out on both the dengue virus ns3pro and ns2b-ns3pro systems. the results revealed that the ns2b-ns3pro complex is more rigid than ns3pro alone due to its robust hydrogen bond and hydrophobic interaction n ... | 2009 | 18971276 |
| recognition of rna cap in the wesselsbron virus ns5 methyltransferase domain: implications for rna-capping mechanisms in flavivirus. | the mrna-capping process starts with the conversion of a 5'-triphosphate end into a 5'-diphosphate by an rna triphosphatase, followed by the addition of a guanosine monophosphate unit in a 5'-5' phosphodiester bond by a guanylyltransferase. methyltransferases are involved in the third step of the process, transferring a methyl group from s-adenosyl-l-methionine to n7-guanine (cap 0) and to the ribose 2'oh group (cap 1) of the first rna nucleotide; capping is essential for mrna stability and prop ... | 2009 | 18976670 |
| west nile virus ns2b/ns3 protease as an antiviral target. | west nile virus (wnv) has spread rapidly during the last decade across five continents causing disease and fatalities in humans and mammals. it highlights the serious threat to both our health and the economy posed by viruses crossing species, in this case from migratory birds via mosquitoes to mammals. there is no vaccine or antiviral drug for treating wnv infection. one attractive target for antiviral development is a viral trypsin-like serine protease, encoded by the n-terminal 184 amino acid ... | 2008 | 18991636 |
| 2-arylbenzimidazoles as antiviral and antiproliferative agents. part 1. | being involved in an anti-flaviviridae project, and because of the role played by benzimidazole derivatives as promising inhibitors of the hcv helicase and rna polymerase, as well as of the zn finger transcription factor, we synthesized a new series of 2-arylbenzimidazoles and evaluated them for antiviral activity, as well as for antiproliferative activity. compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the flaviviridae family, i.e. fl ... | 2008 | 18991746 |
| hepatitis c virus ns3/4a protease inhibitors. | chronic hepatitis c virus infection is a global problem worldwide due to the lack of an effective therapy (the current standard of care treatment is effective in about 40-50% of the cases), and the difficulties in developing a protective vaccine. chronic infection progresses to end-stage liver disease and liver failure in a considerable number of infected individuals. once liver function is compromised, the only reliable therapeutic intervention is liver transplantation. unfortunately, re-infect ... | 2008 | 18991798 |