Publications

TitleAbstractYear
Filter
PMID(sorted descending)
Filter
an experimental model of meningoencephalomyelitis by rocio flavivirus in balb/c mice: inflammatory response, cytokine production, and histopathology.abstract. rocio virus (rocv) is a flavivirus, probably transmitted by culex mosquitoes and maintained in nature as a zoonosis of wild birds. rocio virus caused a human epidemic of severe encephalitis that lasted from 1973 to 1980 in the ribeira valley, in the southeastern coast of brazil. after this outbreak, serologic evidence of rocv circulation has been reported and public health authorities are concerned about a return of rocv outbreaks in brazil. we show here a study on the pathogenesis and ...201121813860
safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in flavivirus-naive infants.abstract. a phase i/ii observer-blind, randomized, controlled trial evaluated the safety and immunogenicity of a dengue virus (denv) vaccine candidate in healthy thai infants (aged 12-15 months) without measurable pre-vaccination neutralizing antibodies to denv and japanese encephalitis virus. fifty-one subjects received two doses of either denv (n = 34; four received 1/10th dose) or control vaccine (n = 17; dose 1, live varicella; dose 2, haemophilus influenzae type b). after each vaccine dose, ...201121813857
maturation of dengue virus nonstructural protein 4b in monocytes enhances production of dengue hemorrhagic fever-associated chemokines and cytokines.high levels of viremia and chemokines and cytokines underlie the progression of severe dengue disease. dengue virus (denv) preferentially infects peripheral blood monocytes, which secrete elevated levels of immunomediators in patients with severe disease. further, denv nonstructural proteins (ns) are capable of modifying intracellular signaling, including interferon inhibition. we demonstrate that peak secretions of immunomediators such as il-6, il-8, ip-10, tnfa or ifn? in denv-infected monocyt ...201121810535
novel formulations enhance the thermal stability of live-attenuated flavivirus vaccines.thermal stability is important for the manufacture, distribution and administration of vaccines, especially in tropical developing countries, where particularly adverse field conditions exist. current live-attenuated flavivirus vaccines exhibit relatively poor liquid stability in clinical settings, and clinicians are instructed to discard the yellow fever vaccine 1h after reconstitution. we have identified novel combinations of excipients that greatly enhance the thermal stability of live-attenu ...201121803103
west nile virus aseptic meningitis and stuttering in woman.to the editor: west nile virus (wnv), a mosquito-borne flavivirus, is closely related to st. louis encephalitis virus and japanese encephalitis virus (jev). most cases of wnv have been mild, but neuroinvasive disease has been observed, especially among older persons and immunocompromised persons (1,2). the most common neurologic manifestations of wnv are aseptic meningitis, meningoencephalitis, and encephalitis with or without acute flaccid paralysis (3). other less common neurologic manifestati ...201121801656
bagaza virus in partridges and pheasants, spain, 2010.in september 2010, an unusually high number of wild birds (partridges and pheasants) died in cádiz in southwestern spain. reverse transcription pcr and virus isolation detected flavivirus infections. complete nucleotide sequence analysis identified bagaza virus, a flavivirus with a known distribution that includes sub-saharan africa and india, as the causative agent.201121801633
dengue virus infection in africa.reported incidence of dengue has increased worldwide in recent decades, but little is known about its incidence in africa. during 1960-2010, a total of 22 countries in africa reported sporadic cases or outbreaks of dengue; 12 other countries in africa reported dengue only in travelers. the presence of disease and high prevalence of antibody to dengue virus in limited serologic surveys suggest endemic dengue virus infection in all or many parts of africa. dengue is likely underrecognized and unde ...201121801609
enhancing the utility of a prm/e-expressing chimeric vaccine for japanese encephalitis by addition of the jev ns1 gene.recently, we demonstrated that a single-cycle west nile virus (wnv) named replivax wn could be used to produce a chimeric japanese encephalitis (je) vaccine (replivax je) by replacing the wnv prm/e genes with those of jev. here, we tested if replacement of wnv ns1 gene in replivax je with that of jev (producing triplivax je) could produce a superior vaccine. triplivax je elicited higher anti-e immunity and displayed better efficacy in mice than replivax je. furthermore, triplivax je displayed re ...201121798299
a high-throughput screening assay for the identification of flavivirus ns5 capping enzyme gtp-binding inhibitors: implications for antiviral drug development.there are no effective antivirals currently available for the treatment of flavivirus infection in humans. as such, the identification and characterization of novel drug target sites are critical to developing new classes of antiviral drugs. the flavivirus ns5 n-terminal capping enzyme (ce) is vital for the formation of the viral rna cap structure, which directs viral polyprotein translation and stabilizes the 5' end of the viral genome. the structure of the flavivirus ce has been solved, and a ...201121788392
the pathogenesis of dengue.dengue is an important cause of childhood and adult morbidity in asian and latin american countries and its geographic footprint is growing. the clinical manifestations of dengue are the expression of a constellation of host and viral factors, some acquired, others intrinsic to the individual. the virulence of the virus plus the flavivirus infection history, age, gender and genotype of the host all appear to help shape the severity of infection. similarly, the characteristics of the innate and a ...201121781999
prevalence of antibodies to phleboviruses and flaviviruses in peja, kosovo.clin microbiol infect 2011; 17: 1180-1182 abstract: in order to investigate the current and past activity of phlebovirus and flavivirus in kosovo, a seroprevalence study among 200 blood donors was performed. positive results were obtained for the phleboviruses tosv and sfnv, and for a flavivirus of the japanese encephalitis group. no positive results for tbev were observed.201121781206
north american west nile viral genotype isolates demonstrate differential replicative capacity in response to temperature.west nile virus (wnv) was first documented in california during the summer of 2003, and the virus has subsequently become endemic throughout the state. sequence analysis has demonstrated that the circulating strains are representative of the north american (wn02) genotype that has displaced the invading east coast genotype (ny99). a recent study has indicated that enhanced vector competence at elevated temperatures may have played a role in the displacement of the east coast genotype by wn02. in ...201121775581
rna binding property and rna chaperone activity of dengue virus core protein and other viral rna-interacting proteins.in this study we showed that the dengue virus (denv) core protein forms a dimer with an a-helix-rich structure, binds rna and facilitates the strand annealing process. to assess the rna chaperone activity of this core protein and other dengue viral rna-interacting proteins, such as ns3 helicase and ns5 proteins, we engineered cis- and trans-cleavage hammerhead ribozyme constructs carrying denv genomic rna elements. our results indicate that denv core protein facilitates typical hammerhead struct ...201121771593
serologic evidence of west nile virus in wild ducks captured in major inland resting sites for migratory waterfowl in south korea.the rapid global expansion of west nile virus (wnv) has recently raised concerns regarding its possible spread into south korea. to date, wnv infection in wild birds in south korea has not been identified. bird migration is thought to be involved in spreading wnv, and wild birds are the possible routes of introduction of wnv infection. to assess the risk of wnv infection in south korea, we conducted a nationwide wnv surveillance of wild birds, with an emphasis on migratory ducks from wnv-affecte ...201121767922
the interaction of flavivirus m protein with light chain tctex-1 of human dynein plays a role in late stages of virus replication.the role of the membrane protein (prm/m) in flavivirus life cycle remains unclear. here, we identified a cellular interactor to the 40-residue-long ectodomain of prm/m (ectom) using a yeast two-hybrid screen against a human cdna library and gst pull-down assays. we showed that dynein light chain tctex-1 interacts with the ectom of dengue 1-4, west nile, and japanese encephalitis flaviviruses. no interaction was found with yellow fever and tick-borne flaviviruses. this interaction is highly speci ...201121767858
west nile virus infection in the united states: overview as a public health issue.in august 1999, west nile virus (wnv), a mosquito-transmitted flavivirus, appeared in new york city. this represented the first time a major outbreak of this old world virus caused an epidemic in the western hemisphere. by december 2002, the outbreak had spread, probably via avian migratory flyways, to involve 44 states and the district of columbia. the future epidemiology of wnv infection in the united states will be difficult to forecast. in the absence of an effective human vaccine, the only ...200321765762
a case of aseptic meningitis due to japanese encephalitis virus in a traveller returning from the philippines.we here report the case of japanese encephalitis virus (jev) meningitis in a previously healthy young women returning from a trip to the philippines. jev is a mosquito-borne encephalitic flavivirus pathogen, which is endemic in south east and eastern asia. our patient presented with aseptic meningitis and recovered well under supportive therapy. although the chance of a traveller getting symptomatic jev infection is extremely low, clinicians and microbiologist should be aware of patients contrac ...201121748935
[saint louis encephalitis virus in buenos aires city during the outbreak of dengue in 2009.]we report the case of a male, 80-year-old resident in the city of buenos aires, with a diagnosis of st. louis encephalitis (sle) during a countrywide dengue outbreak, from january to may 2009. the patient had a chronic lymphocytic leukemia treated with chlorambucil, prostate cancer (hormone therapy and radiotherapy) and images consistent with bone metastases. cerebrospinal fluid examination showed pleocytosis with a predominance of mononuclear cells and high protein concentration. bacteria, fung ...201121745774
from research to phase iii: preclinical, industrial and clinical development of the sanofi pasteur tetravalent dengue vaccine.dengue vaccine development has reached a major milestone with the initiation, in 2010, of the first phase iii clinical trial to investigate the sanofi pasteur cyd tetravalent dengue vaccine (tdv). the cyd tdv candidate is composed of four recombinant, live, attenuated vaccines (cyd-1-4) based on a yellow fever vaccine 17d (yfv 17d) backbone, each expressing the pre-membrane and envelope genes of one of the four dengue virus serotypes. the vaccine is genetically and phenotypically stable, non-hep ...201121745521
interference and facilitation between dengue serotypes in a tetravalent live dengue virus vaccine candidate.live, multivalent vaccines have historically exhibited interference in humans; live dengue virus (denv) vaccines have proven no exception.201121742844
neutralising antibodies for west nile virus in horses from brazilian pantanal.despite evidence of west nile virus (wnv) activity in colombia, venezuela and argentina, this virus has not been reported in most south american countries. in february 2009, we commenced an investigation for wnv in mosquitoes, horses and caimans from the pantanal, central-west brazil. the sera of 168 horses and 30 caimans were initially tested using a flaviviruses-specific epitope-blocking enzyme-linked immunosorbent assay (blocking elisa) for the detection of flavivirus-reactive antibodies. the ...201121739036
a dynamic landscape for antibody binding modulates antibody-mediated neutralization of west nile virus.neutralizing antibodies are a significant component of the host's protective response against flavivirus infection. neutralization of flaviviruses occurs when individual virions are engaged by antibodies with a stoichiometry that exceeds a required threshold. from this "multiple-hit" perspective, the neutralizing activity of antibodies is governed by the affinity with which it binds its epitope and the number of times this determinant is displayed on the surface of the virion. in this study, we ...201121738473
west nile and usutu viruses in mosquitoes in spain, 2008-2009.west nile virus lineage 1 (similar to the strains obtained from golden eagles in spain, 2007) and usutu virus (similar to the strains obtained from culex pipiens in spain, 2006) were detected in pools from culex perexiguus collected in southern spain in 2008 and 2009, respectively. this is the first detection and isolation of west nile virus lineage 1 from mosquitoes in spain.201121734145
insect-specific flaviviruses from culex mosquitoes in colorado, with evidence of vertical transmission.mosquitoes were collected in colorado during 2006 and 2007 to examine spatial and seasonal patterns of risk for exposure to culex vectors and west nile virus. we used universal flavivirus primers to test pools of culex mosquitoes for viral rna. this led to the detection and subsequent isolation of two insect-specific flaviviruses: culex flavivirus (cxfv), which was first described from japan, and a novel insect flavivirus, designated calbertado virus (clbov), which has also been detected in cali ...201121734144
distribution and phylogenetic comparisons of a novel mosquito flavivirus sequence present in culex tarsalis mosquitoes from western canada with viruses isolated in california and colorado.in a previous study, a new flavivirus genome sequence was identified in culex tarsalis mosquitoes obtained in alberta, canada and was shown to be genetically related to but distinct from members of the insect-specific flaviviruses. nonstructural protein 5-encoding sequences amplified from cx. tarsalis pools from western canada have shown a high similarity to genome sequences of novel flaviviruses isolated from mosquitoes in california and colorado. despite wide distribution of this virus, design ...201121734143
determinants of attenuation in the envelope protein of the flavivirus alfuy.murray valley encephalitis virus (mvev) is a mosquito-borne flavivirus endemic to australia and papua new guinea. most strains of mvev cause potentially fatal cases of encephalitis in humans and horses, and have been shown to be highly neuroinvasive in weanling mice. in contrast, the naturally-occurring subtype alfuy virus (alfv) has never been associated with human disease, nor is it neuroinvasive in weanling mice, even at high doses. to identify viral factors associated with alfv attenuation, ...201121733886
modulation of the immune-related gene responses to protect mice against japanese encephalitis virus using the antimicrobial peptide, tilapia hepcidin 1-5.japanese encephalitis virus (jev), a neurotropic flavivirus, is one of the major causes of acute encephalitis in humans. after infection, it is commonly associated with inflammatory reactions and neurological disease. there is still no effective antiviral drug available against japanese encephalitis virus infection. recently, a number of investigators found that antimicrobial peptide (amps) present a broad range of biological activities including antimicrobial and immunomodulatory activities. in ...201121726898
an infectious disease of ducks caused by a newly emerged tembusu virus strain in mainland china.during investigations into an outbreak of egg production decline, retarded growth, and even death among ducks in southeast china, a novel tembusu virus strain named tembusu virus fengxian 2010 (fx2010) was isolated. this virus replicated in embryonated chicken eggs and caused embryo death. in cross-neutralization tests, antiserum to the partial e protein of tembusu virus mm1775 strain neutralized fx2010, whereas antiserum to japanese encephalitis virus did not. fx2010 is an enveloped rna virus o ...201121722935
vimentin binding is critical for infection by the virulent strain of japanese encephalitis virus.japanese encephalitis virus (jev), a mosquito-borne flavivirus, causes acute encephalitis with high mortality in humans. we used a pair of virulent (rp-9) and attenuated (rp-2ms) variants of jev to pull down the cell surface molecules bound with jev particle; their identities were revealed by lc-ms/ms analysis. one major protein bound with rp-9 and weakly with rp-2ms was identified as the intermediate filament protein vimentin. infection of rp-9 but not that of rp-2ms was blocked by anti-vimenti ...201121707907
a specific and sensitive antigen capture assay for ns1 protein quantitation in japanese encephalitis virus infection.japanese encephalitis virus (jev) is a human pathogenic, mosquito-borne flavivirus that is endemic/epidemic in asia. jev is rarely detected or isolated from blood or cerebrospinal fluid (csf), and detection of igm is generally diagnostic of the infection. the flavivirus nonstructural glycoprotein ns1 is released transiently during flavivirus replication. the aim of this study was to set up a quantitative jev ns1 antigen capture assay. a soluble hexameric form of jev ns1 protein was produced in a ...201121704081
use of a tandem affinity purification assay to detect interactions between west nile and dengue viral proteins and proteins of the mosquito vector.west nile and dengue viruses are (re)emerging mosquito-borne flaviviruses that cause significant morbidity and mortality in man. the identification of mosquito proteins that associate with flaviviruses may provide novel targets to inhibit infection of the vector or block transmission to humans. here, a tandem affinity purification (tap) assay was used to identify 18 mosquito proteins that interact with dengue and west nile capsid, envelope, ns2a or ns2b proteins. we further analyzed the interact ...201121700306
mutational analysis of the zippering reaction during flavivirus membrane fusion.the current model of flavivirus membrane fusion is based on atomic structures of truncated forms of the viral fusion protein e in its dimeric prefusion and trimeric postfusion conformations. these structures lack the two transmembrane domains (tmds) of e as well as the so-called stem, believed to be involved in an intra- and intermolecular zippering reaction within the e trimer during the fusion process. in order to gain experimental evidence for the functional role of the stem in flavivirus mem ...201121697495
prm-antibody renders immature west nile virus infectious in vivo.west nile virus (wnv) is a member of the flaviviridae and a neurotropic pathogen responsible for severe human disease. flavivirus infected cells release virus particles that contain variable numbers of precursor membrane (prm) protein molecules at the viral surface. consequently, antibodies are produced against the prm protein. these antibodies have been shown to activate the infectious potential of fully immature flavivirus particles in vitro. here, we provide in vivo proof that prm antibodies ...201121697345
acute hepatitis a virus infection is associated with a limited type i interferon response and persistence of intrahepatic viral rna.hepatitis a virus (hav) is an hepatotropic human picornavirus that is associated only with acute infection. its pathogenesis is not well understood because there are few studies in animal models using modern methodologies. we characterized hav infections in three chimpanzees, quantifying viral rna by quantitative rt-pcr and examining critical aspects of the innate immune response including intrahepatic ifn-stimulated gene expression. we compared these infection profiles with similar studies of c ...201121690403
charged residues in hepatitis c virus ns4b are critical for multiple ns4b functions in rna replication.the nonstructural 4b (ns4b) protein of hepatitis c virus (hcv) plays a central role in the formation of the hcv replication complex. to gain insight into the role of charged residues for ns4b function in hcv rna replication, alanine substitutions were engineered in place of 28 charged residues residing in the n- and c-terminal cytoplasmic domains of the ns4b protein of the hcv genotype 1b strain con1. eleven single charged-to-alanine mutants were not viable, while the remaining mutants were repl ...201121680530
the viruses of australia and the risk to tourists.australia is a climatically diverse country varying from a tropical climate in the north to arid central desert and grassland regions, and to temperate climates in the south. there are many viral infections found in australia that are common to developed countries worldwide, but this article will focus on those that pose a special risk for travellers to australia, especially the mosquito-borne viruses. the commonest are the members of the alphavirus genus, particularly ross river virus and barma ...201121679887
vector competence of the stable fly (diptera: muscidae) for west nile virus.in 2006-2007, stable flies, stomoxys calcitrans (l.) (diptera: muscidae), were suspected of being enzootic vectors of west nile virus (family flaviviridae, genus flavivirus, wnv) during a die-off of american white pelicans (pelecanus erythrorhynchos gmelin) (pelecanidae) in montana, usa. wnv-positive stable flies were observed feeding en masse on incapacitated, wnv-positive pelicans, arousing suspicions that the flies could have been involved in wnv transmission among pelicans, and perhaps to li ...201121661328
microclimate and the zoonotic cycle of tick-borne encephalitis virus in switzerland.the focal distribution of tick-borne encephalitis virus (tbev; flaviviridae, flavivirus) appears to depend mainly on cofeeding transmission between infected ixodes ricinus l. nymphs and uninfected larvae. to better understand the role of cofeeding ticks in the transmission of tbev, we investigated tick infestation of rodents and the influence of microclimate on the seasonality of questing i. ricinus ticks. a 3-yr study was carried out at four sites, including two confirmed tbev foci. free-living ...201121661323
[kunjin virus replicon--a novel viral vector].viral replicon is a kind of self-replicating viral rna sourced from viral genome, which contains viral non-structural genes that are critical for viral genome replication with structural proteins deleted or replaced by foreign genes. kunjin virus is a member of the flavivirida family, flavivirus genus, and kunjin virus replicon is the first and the clearly defined flavivirus replicon. kunjun virus replicon has been regarded as an excellent viral vector on account of its high expression, lower cy ...201121650037
mutational analysis of three predicted 5'-proximal stem-loop structures in the genome of tick-borne encephalitis virus indicates different roles in rna replication and translation.flavivirus gene expression is modulated by rna secondary structure elements at the terminal ends of the viral rna molecule. for tick-borne encephalitis virus (tbev), four stem-loop (sl) elements have been predicted in the first 180 nucleotides of the viral genome: 5'-sl1, 5'-sl2, 5'-sl3 and 5'-sl4. the last three of these appear to be unique to tick-borne flaviviruses. here, we report their characterization by mutagenesis in a tbev luciferase reporter system. by manipulating their thermodynamic ...201121645915
binding of flavivirus nonstructural protein ns1 to c4b binding protein modulates complement activation.the complement system plays a pivotal protective role in the innate immune response to many pathogens including flaviviruses. flavivirus nonstructural protein 1 (ns1) is a secreted nonstructural glycoprotein that accumulates in plasma to high levels and is displayed on the surface of infected cells but absent from viral particles. previous work has defined an immune evasion role of flavivirus ns1 in limiting complement activation by forming a complex with c1s and c4 to promote cleavage of c4 to ...201121642539
ns3 protease from flavivirus as a target for designing antiviral inhibitors against dengue virus.the development of novel therapeutic agents is essential for combating the increasing number of cases of dengue fever in endemic countries and among a large number of travelers from non-endemic countries. the dengue virus has three structural proteins and seven non-structural (ns) proteins. ns3 is a multifunctional protein with an n-terminal protease domain (ns3pro) that is responsible for proteolytic processing of the viral polyprotein, and a c-terminal region that contains an rna triphosphatas ...201021637471
a single amino acid in nonstructural ns4b protein confers virulence to dengue virus in ag129 mice through enhancement of viral rna synthesis.dengue (den) is a mosquito borne viral disease which has become an increasing economic and health burden for the tropical and subtropical world. the lack of an appropriate animal model of den has greatly impeded pathogenesis study and vaccine/antiviral development. we recently reported a den virus (denv)-2 strain (d2y98p) that lethally infects immunocompromised ag129 mice, resulting in organ damage or dysfunction, and increased vascular permeability, hallmarks of severe den in patients. here we ...201121632767
comparison of argentinean saint louis encephalitis virus non-epidemic and epidemic strain infections in an avian model.st. louis encephalitis virus (slev, flavivirus, flaviviridae) is an emerging mosquito-borne pathogen in south america, with human slev encephalitis cases reported in argentina and brazil. genotype iii strains of slev were isolated from culex quinquefasciatus mosquitoes in cordoba, argentina in 2005, during the largest slev outbreak ever reported in south america. the present study tested the hypothesis that the recent, epidemic slev strain exhibits greater virulence in birds as compared with a n ...201121629729
replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the flavivirus genus.we provide experimental evidence of a replication enhancer element (ree) within the capsid gene of tick-borne encephalitis virus (tbev, genus flavivirus). thermodynamic and phylogenetic analyses predicted that the ree folds as a long stable stem-loop (designated sl6), conserved among all tick-borne flaviviruses (tbfv). homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. to invest ...201121622960
characterization of the replivax platform for replication-defective flavivirus vaccines.replivax, a novel replication-defective vaccine platform has recently been described as a suitable means of generating potent vaccines targeting flaviviruses. in this study, we directly compared attenuation, immunogenicity and efficacy of several prototype replivax constructs to available, well characterized live attenuated (lav) and inactivated (inv) flavivirus vaccine controls in mice and hamsters. other important aspects of general mechanisms and properties of replivax vaccines were also stud ...201121620917
yellow fever virus envelope protein expressed in insect cells is capable of syncytium formation in lepidopteran cells and could be used for immunodetection of yfv in human sera.abstract: background: yellow fever is an haemorrhagic disease caused by a virus that belongs to the genus flavivirus (flaviviridae family) and is transmitted by mosquitoes. among the viral proteins, the envelope protein (e) is the most studied one, due to its high antigenic potencial. baculovirus are one of the most popular and efficient eukaryotic expression system. in this study a recombinant baculovirus (vsynyfe) containing the envelope gene (env) of the 17d vaccine strain of yellow fever vir ...201121619598
targeting c-type lectin for the treatment of flavivirus infections. 201121618140
recommendations for use of a booster dose of inactivated vero cell culture-derived japanese encephalitis vaccine --- advisory committee on immunization practices, 2011.japanese encephalitis (je) virus, a mosquito-borne flavivirus, is an important cause of encephalitis in asia with a case fatality rate of 20%--30% and neurologic or psychiatric sequelae in 30%--50% of survivors (1). travelers to je-endemic countries and laboratory personnel who work with infectious je virus are at potential risk for je virus infection. in 2010, cdc's advisory committee on immunization practices (acip) updated recommendations for prevention of je. the updated recommendations incl ...201121617632
an investigation of phenylthiazole antiflaviviral agents.flaviviruses are one of the most clinically important pathogens and their infection rates are increasing steadily. the phenylthiazole ring system has provided a template for the design and synthesis of antiviral agents that inhibit the flaviviruses by targeting their e-protein. unfortunately, there is a correlation between phenylthiazole antiflaviviral activity and the presence of the reactive and therefore potentially toxic mono- or dibromomethyl moieties at thiazole-c4. adding a linear hydroph ...201121612931
emerging vector-borne flavivirus diseases: are vaccines the solution? 201121604976
a dna vaccine encoding the e protein of west nile virus is protective and can be boosted by recombinant domain diii.west nile virus (wnv) is an emerging pathogenic flavivirus with increasing distribution worldwide. birds are the natural host of the virus, but also mammals, including humans, can be infected. in some cases, a wnv infection can be associated with severe neurological symptoms. all currently available wnv vaccines are in the veterinary sector, and there is a need to develop safe and effective immunization technologies, which can also be used in humans. an alternative to current vaccination methods ...201121596075
dynamic rna structures in the dengue virus genome.dengue virus is an important human pathogen that belongs to the flaviviridae family. the viral genome is a single molecule of rna of positive polarity that plays multiple roles during the viral life cycle. besides encoding the viral proteins, the genome contains rna structures that regulate different viral processes. an important feature of dengue and other flavivirus genomes is the presence of inverted complementary sequences at the ends of the molecule that mediate long-range rna-rna interacti ...201121593583
maturation of flaviviruses starts from one or more icosahedrally independent nucleation centres.flaviviruses assemble as fusion-incompetent immature particles and subsequently undergo conformational change leading to release of infectious virions. flavivirus infections also produce combined 'mosaic' particles. here, using cryo-electron tomography, we report that mosaic particles of dengue virus type 2 had glycoproteins organized into two regions of mature and immature structure. furthermore, particles of a maturation-deficient mutant had their glycoproteins organized into two regions of im ...201121566648
small molecule pan-dengue and west nile virus ns3 protease inhibitors.dengue fever, dengue haemorrhagic fever, and dengue shock syndrome are caused by infections with any of the four serotypes of the dengue virus (denv), and are an increasing global health risk. the related west nile virus (wnv) causes significant morbidity and mortality as well, and continues to be a threat in endemic areas. currently no fda-approved vaccines or therapeutics are available to prevent or treat any of these infections. like the other members of flaviviridae, denv and wnv encode a pr ...201121566267
hiding from intracellular pattern recognition receptors, a passive strategy of flavivirus immune evasion.tick-borne encephalitis virus (tbev) is a medically important flavivirus in europe and asia, causing meningitis and encephalitis in thousands of people annually. despite its relevance for public health, the interaction of tbev with the type i interferon (ifn) system is poorly characterized. induction of these antiviral cytokines is normally triggered by cytoplasmic recognition of viral signature molecules such as double-stranded (ds) rna. in a recent paper, we showed that tbev infection leads to ...201121555916
usutu virus in italy: an emergence or a silent infection?a two year study (2008-2009) was carried out to monitor the usutu virus (usuv) circulation in italy. sentinel horses and chickens, wild birds and mosquitoes were sampled and tested for the presence of usuv and usuv antibodies within the wnd national surveillance plan. seroconversion evidenced in sentinel animals proved that in these two years the virus has circulated in tuscany, emilia romagna, veneto and friuli venezia giulia regions. in veneto usuv caused a severe blackbird die-off disease inv ...201121550731
immune responses to an attenuated west nile virus ns4b-p38g mutant strain.the nonstructural (ns) proteins of west nile virus (wnv) have been associated with participation in evasion of host innate immune defenses. in the present study, we characterized immune response to an attenuated wnv strain, which has a p38g substitution in the ns4b protein. the wnv ns4b-p38g mutant induced a lower level of viremia and no lethality in c57bl/6 (b6) mice following a systemic infection. interestingly, there were higher type 1 ifns and il-1β responses compared to mice infected by wil ...201121549792
the current perspective on tick-borne encephalitis awareness and prevention in six central and eastern european countries: report from a meeting of experts convened to discuss tbe in their region.tick-borne encephalitis (tbe) is a potentially life-threatening disease in humans and is caused by a flavivirus spread by infected ticks (ixodes ricinus and ixodes persulcatus). tbe is endemic across much of central and eastern europe and the incidence is increasing, with numbers estimated to be as many as 8755 cases per year. the reasons for this increase are multi-faceted and may involve improvements in diagnosis and reporting of tbe cases, increases in recreational activities in areas inhabit ...201121549781
protection provided by a recombinant alvac(®)-wnv vaccine expressing the prm/e genes of a lineage 1 strain of wnv against a virulent challenge with a lineage 2 strain.the emergence of lineage 2 strains of wnv in europe as a cause of clinical disease and mortality in horses raised the question whether the existing wnv vaccines, all based on lineage 1 strains, protect against circulating lineage 2 strains of wnv. in the present paper we have determined the level of cross protection provided by the recombinant alvac(®)-wnv vaccine in a severe challenge model that produces clinical signs of wnv type 2 disease. ten horses were vaccinated twice at 4 weeks interval ...201121549780
characterization of nonstructural protein 3 of a neurovirulent japanese encephalitis virus strain isolated from a pig.abstract:201121549011
rodents as sentinels for the prevalence of tick-borne encephalitis virus.abstract introduction: tick-borne encephalitis virus (tbev) causes one of the most important flavivirus infections of the central nervous system, affecting humans in europe and asia. it is mainly transmitted by the bite of an infected tick and circulates among them and their vertebrate hosts. until now, tbe risk analysis in germany has been based on the incidence of human cases. because of an increasing vaccination rate, this approach might be misleading, especially in regions of low virus circu ...201121548766
expression of recombinant west nile virus prm protein fused to an affinity tag for use as a diagnostic antigen.previous studies have concluded that the flavivirus prm protein is a suitable viral antigen to distinguish serologically between infections with closely related flaviviruses (cardosa et al., 2002). to express the recombinant west nile virus (wnv) prm antigen fused to a suitable affinity tag for purification, a series of prm-his-tag and prm-v5-tag fusion proteins were generated. analysis of the prm-his-tag fusion proteins revealed that either prm epitopes were disrupted or the his-tag was not pre ...201121545809
ns4b self-interaction through conserved c-terminal elements is required for the establishment of functional hcv replication complexes.hepatitis c virus (hcv) is an important human pathogen, persistently infecting more than 170 million individuals worldwide. studies of the hcv life cycle have become possible with the development of cell culture systems supporting replication of viral rna and production of infectious virus. however, the exact functions of individual proteins, especially of non-structural protein 4b (ns4b), remain poorly understood. ns4b triggers the formation of specific, vesicular membrane rearrangements, desig ...201121543474
pathogenesis of japanese encephalitis virus infection in a golden hamster model and evaluation of flavivirus cross-protective immunity.abstract. japanese encephalitis virus (jev) is a mosquito-borne flavivirus endemic to southeast asia and surrounding pacific islands, and it has most recently emerged in northern australia. jev is closely related to west nile virus (wnv) and st. louis encephalitis virus (slev), both endemic to the united states. in the event that jev is introduced into the americas, it will be important to determine whether immunity to wnv or slev might afford protection from infection and development of viremia ...201121540381
specific detection of antibodies to different flaviviruses using a new immune complex elisa.immune complex (ic) elisas for igg antibodies to various virus antigens have turned out to be both highly specific and sensitive. during incubation of a labelled antigen with the serum samples, ics are formed, which bind to microtiter plates coated with rheumatoid factor (rf) igm. here, we describe an improved coating of the solid-phase support comparing various fc-receptor molecules. ic elisas were applied to detect human igg antibodies to the highly virus-specific ed3 domain of west nile- and ...201121533786
phylogenetic analysis of west nile virus isolates, italy, 2008-2009.to determine the lineage of west nile virus that caused outbreaks in italy in 2008 and 2009, several west nile virus strains were isolated from human specimens and sequenced. on the basis of phylogenetic analyses, the strains isolated constitute a distinct group within the western mediterranean cluster.201121529408
probable non-vector-borne transmission of zika virus, colorado, usa.clinical and serologic evidence indicate that 2 american scientists contracted zika virus infections while working in senegal in 2008. one of the scientists transmitted this arbovirus to his wife after his return home. direct contact is implicated as the transmission route, most likely as a sexually transmitted infection.201121529401
cross protection against lethal west nile virus challenge in mice immunized with recombinant e protein domain iii of japanese encephalitis virus.japanese encephalitis virus (jev) and west nile virus (wnv) are closely related mosquito-borne flaviviruses that cause severe encephalitic diseases with global impact. cross protection among jev and wnv has been previously described, and most cross reactive epitopes were identified within the domain ii of e protein (edii). in this study, the e protein domain iii (ediii) of jev was successfully expressed in escherichia coli, purified by a ni-nta column and characterized by western blotting assay. ...201121515306
maprec assay for quantitation of mutants in a recombinant flavivirus vaccine strain using near-infrared fluorescent dyes.mutant analysis by pcr and restriction enzyme cleavage (maprec) is a quantitative assay of revertants in batches of live viral vaccines. the assay is highly sensitive and reliable but requires radioactive isotopes, which complicates its use in quality control laboratories. to quantify mutants in the cdna of the west nile (wn)/dengue 4 chimera that was proposed as a new candidate of live vaccine against west nile disease, alternative maprec protocols using non-radioactive dyes were explored. to c ...201121514323
flavivirus ns4a-induced autophagy protects cells against death and enhances virus replication.flaviviruses include the most prevalent and medically challenging viruses. persistent infection with flaviviruses of epithelial cells and hepatocytes that do not undergo cell death is common. here we report that, in epithelial cells, upregulation of autophagy following flavivirus infection markedly enhances virus replication, and that one flavivirus gene, ns4a, uniquely determines the upregulation of autophagy. dengue-2 and modoc (a murine flavivirus) kill primary murine macrophages but protect ...201121511946
inhibition of dengue virus through suppression of host pyrimidine biosynthesis.viral replication relies on host to supply nucleosides. host enzymes involved in nucleoside biosynthesis are potential targets for antiviral development. ribavirin (a known antiviral drug) is such an inhibitor that suppresses guanine biosynthesis; depletion of intracellular gtp pool was shown to be the major mechanism to inhibit flavivirus. along a similar concept, inhibitors of pyrimidine biosynthesis pathway could be targeted for potential antiviral development. here we report a novel antivira ...201121507975
conserved gxxxg- and s/t-like motifs in the transmembrane domains of ns4b protein are required for hepatitis c virus replication.hepatitis c virus (hcv) nonstructural 4b (ns4b) is an integral membrane protein, which plays an important role in the organization and function of the hcv replication complex (rc). although a lot is understood about its amphipathic n-terminal and c-terminal domains, we know very little regarding the role of the transmembrane domains (tmds) in ns4b function. we hypothesized that in addition to anchoring ns4b into host membranes, the tmds are engaged in intra- and intermolecular interactions requi ...201121507970
hyperkinetic movement disorders associated with hiv and other viral infections.viral infections of the central nervous system often result in a spectrum of movement disorders, ranging from slowness and rigidity to hyperkinetic movements such as chorea, ballism, dystonia, and myoclonus. the basal ganglia are especially susceptible to some viruses, because of their intrinsic neurotropism, a predilection of opportunistic infections for the deep gray matter of the brain, and possibly the mounting of an autoimmune response against basal ganglia antigens. viral encephalitides re ...201121496592
partial protection against classical swine fever virus elicited by dendrimeric vaccine-candidate peptides in domestic pigs.we report the immunogenicity of three dendrimeric peptide vaccine candidates for classical swine fever virus (csfv). each dendrimeric construct contained four copies of a b-cell epitope from the e2 glycoprotein of csfv [construct 1: e2 (694-712); 2: e2 (712-727); 3: e2 (829-842)] joined to a t-cell epitope from the ns3 protein (residues 1446-1460). intramuscular immunization of domestic pigs with the different constructs significantly reduced the clinical score after lethal challenge with csfv. ...201121496472
blood-feeding patterns of the culex pipiens complex in sacramento and yolo counties, california.mosquitoes in the culex pipiens complex are competent vectors of west nile virus (wnv; family flaviviridae, genus flavivirus) in the laboratory, and field-collected mosquitoes have tested positive for the virus in california and elsewhere. a better understanding of cx. pipiens complex blood-feeding patterns will help define the threat that these mosquitoes pose to human health and their role in wnv amplification in northern california. we collected blood-engorged cx. pipiens complex mosquitoes f ...201121485380
identification of a cryptic prokaryotic promoter within the cdna encoding the 5' end of dengue virus rna genome.infectious cdna clones of rna viruses are important research tools, but flavivirus cdna clones have proven difficult to assemble and propagate in bacteria. this has been attributed to genetic instability and/or host cell toxicity, however the mechanism leading to these difficulties has not been fully elucidated. here we identify and characterize an efficient cryptic bacterial promoter in the cdna encoding the dengue virus (denv) 5' utr. following cryptic transcription in e. coli, protein express ...201121483867
[combined effects of immunomodulators and specific inactivated vaccines against alpha- and flavivirus infections].the combined effects of immunomodulators, such as ridostin, polyribonate, glucose muramyl dipeptide, and peptidoglycan-160, and specific vaccines on survival of mice with alpha- (eastern equine encephalitis) and flavivirus (tick-borne encephalitis (tbe) infections were found to be significant. in alphavirus infection, the combined effects of the specific vaccine and ridostin were accompanied by increases in specific humoral immunity (specific antibodies) and cellular immunity (adoptive transfer ...201121480553
live-attenuated, tetravalent dengue vaccine in children, adolescents and adults in a dengue endemic country: randomized controlled phase i trial in the philippines.a recombinant live attenuated tetravalent dengue vaccine (tdv) is safe and immunogenic in adults and children in dengue-naïve populations. data are needed in dengue endemic populations. in a phase i, randomized, controlled, blind-observer study in the philippines, groups of participants aged 2-5, 6-11, 12-17, and 18-45 years received either three tdv vaccinations at months 0, 3.5, and 12 (tdv-tdv-tdv group) or licensed typhoid vaccination at month 0 and tdv at months 3.5 and 12 (tyvi-tdv-tdv gro ...201121477675
[inhibitors of hepatitis c virus--therapeutic possibilities].the search for new drugs against hcv contains new ways to obtain pro-drugs which inhibit translation and block viral proteins, and inhibit host proteins important in hcv-induced pathogenesis. this group of agents are serine protease ns3 inhibitors (telaprevir, boceprevir, r-7227, tmc-435, sch 900518, gs-9256). the most advanced studies are developed with telaprevir and boceprevir; at present their effect in combined therapy with pegifn-alpha and rbv in the iii clinical phase is tested. the susta ...201021473061
the f1 motif of dengue virus polymerase ns5 is involved in promoter-dependent rna synthesis.the mechanism by which viral rna-dependent rna polymerases (rdrp) specifically amplify viral genomes is still unclear. in the case of flaviviruses, a model has been proposed that involves the recognition of an rna element present at the viral 5' untranslated region, stem-loop a (sla), that serves as a promoter for ns5 polymerase binding and activity. here, we investigated requirements for specific promoter-dependent rna synthesis of the dengue virus ns5 protein. using mutated purified ns5 recomb ...201121471248
seroprevalence of west nile virus in feral horses on sheldon national wildlife refuge, nevada, united states.we screened 1,397 feral horses (equus caballus) on sheldon national wildlife refuge, nevada, united states, for igm and igg against flavivirus during 2004-2006, 2008, and 2009. positive serum samples were tested for neutralizing antibodies to west nile virus (wnv) and st. louis encephalitis virus (slev). one animal was positive for antibody against wnv in 2004, but all others tested in 2004-2006 were negative. in 2008 and 2009, we found evidence of increasing seropositive horses with age, wherea ...201121460023
duck egg-drop syndrome caused by byd virus, a new tembusu-related flavivirus.since april 2010, a severe outbreak of duck viral infection, with egg drop, feed uptake decline and ovary-oviduct disease, has spread around the major duck-producing regions in china. a new virus, named byd virus, was isolated in different areas, and a similar disease was reproduced in healthy egg-producing ducks, infecting with the isolated virus. the virus was re-isolated from the affected ducks and replicated well in primary duck embryo fibroblasts and vero cells, causing the cytopathic effec ...201121455312
purification and concentration of non-infectious west nile virus-like particles and infectious virions using a pseudo-affinity cellufine sulfate column.affinity column chromatography is a promising method for the purification of flavivirus particles that can supplement or potentially replace diafiltration and sucrose density centrifugation. in this study, the purification of west nile virus (wnv) antigens via cellufine sulfate column chromatography was examined. virus-like particles (vlps) produced by the expression of the prm and e genes were separated from most of the contaminant proteins with 0.2-0.4m nacl, but still retained their spherical ...201121440004
first serological evidence of west nile virus activity in horses in serbia.abstract west nile virus (wnv), the most widely distributed flavivirus worldwide, has lately reemerged in europe, causing worrisome outbreaks in humans and horses. serological analysis by enzyme-linked immunoassay and plaque reduction neutralization test showed for the first time in serbia that 12% of 349 horses presented specific neutralizing wnv antibodies, which in one case also cross-neutralized usutu virus (usuv). this is the first time that anti-usuv high neutralizing antibody titers are r ...201121438694
new japanese encephalitis vaccines: alternatives to production in mouse brain.japanese encephalitis virus (jev), a flavivirus maintained in a zoonotic cycle and transmitted by the mosquito culex tritaeniorhynchus, causes epidemics of encephalitis throughout much of asia. resident populations, including short- or long-term visitors to enzootic regions, are at risk of infection and disease. for the past several decades, killed viral vaccines prepared in tissue culture or mouse brain have been used effectively to immunize travelers and residents of enzootic countries. cost, ...201121434803
small molecule drug discovery for dengue and west nile viruses: applying experience from hepatitis c virus.there are currently no specific treatments for infection with dengue virus (denv) and west nile virus (wnv). drug-discovery programs are underway for both viruses, but as yet no small molecules have advanced to clinical trials. hepatitis c virus (hcv) is a related flavivirus that has been the focus of intense drug discovery efforts for the last two decades. many approaches currently being pursued for denv and wnv have been previously attempted for hcv with varying degrees of success. the experie ...201021426163
silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.west nile (wn) and st. louis encephalitis (sle) viruses can cause fatal neurological infection and currently there is neither a specific treatment nor an approved vaccine for these infections. in our earlier studies, we have reported that sirnas can be developed as broad-spectrum antivirals for the treatment of infection caused by related viruses and that a small peptide called rvg-9r can deliver sirna to neuronal cells as well as macrophages. to increase the repertoire of broad-spectrum antifla ...201121423625
dengue causing fulminant hepatitis in a hepatitis b virus carrier.dengue is an acute febrile illness resulting from infection by a flavivirus transmitted by the aedes mosquito. it is characterized by bleeding manifestations and a plasma leak syndrome. hepatic involvement in the form of elevation in transaminases is common. however, acute hepatic failure is uncommon. it is not known how the presence of an underlying chronic hepatitis or liver disease affects the likelihood of severity of hepatitis from dengue. the present report is of a 33-year-old man, a carri ...201121422600
evaluation of two molecular methods for the detection of yellow fever virus genome.yellow fever virus (yfv), a member of the family flaviviridae, genus flavivirus is endemic to tropical areas of africa and south america and is among the arboviruses that pose a threat to public health. recent outbreaks in brazil, bolivia, and paraguay and the observation that vectors capable of transmitting yfv are presenting in urban areas underscore the urgency of improving surveillance and diagnostic methods. two novel methods (rt-hemi-nested-pcr and sybr(®) green qrt-pcr) for efficient dete ...201121419803
yellow fever virus ns2b/ns3 protease: hydrolytic properties and substrate specificity.here we report the hydrolytic behavior of recombinant yfv ns2b/ns3 protease against fret substrates mimicking the prime and non-prime region of the natural polyprotein cleavage sites. while the p2-p'1 motif is the main factor associated with the catalytic efficiency of dengue (dv) and west nile virus (wnv) protease, we show that the k(cat)/k(m) of yfv ns2b/ns3 varied by more than two orders of magnitude, despite the presence of the same motif in all natural substrates. the catalytic significance ...201121419753
intradermal vaccination to protect against yellow fever and influenza.the viral infections yellow fever and influenza can lead to large epidemics, which may deplete limited vaccine supplies. the intradermal vaccination route of yellow fever and influenza vaccines has received renewed attention, because it allows dose reduction without loss of efficacy. in this chapter, we review these two vaccines, the history of vaccine development, correlates of protection, immune response to vaccination and current knowledge concerning intradermal vaccination, including the imm ...201121416266
medical microbiologyat least 27 alphaviruses and 68 flaviviruses have been recognized, approximately one-third of which are medically important human pathogens. they vary widely in their basic ecology; each virus occupies a distinct ecologic niche, often with restricted geographic and biologic distribution. as shown in tables 54-1 and 54-2, alphaviruses and flaviviruses can cause various syndromes, ranging from benign febrile illnesses to severe system ...199621413253
phylogenetic and virulence analysis of tick-borne encephalitis virus field isolates from switzerland.tick-borne encephalitis (tbe) is an endemic disease in switzerland, with about 110-120 reported human cases each year. endemic areas are found throughout the country. however, the viruses circulating in switzerland have not been characterized so far. in this study, the complete envelope (e) protein sequences and phylogenetic classification of 72 tbe viruses found in ixodes ricinus ticks sampled at 39 foci throughout switzerland were analyzed. all isolates belonged to the european subtype and wer ...201121412794
an amino acid substitution (v3i) in the japanese encephalitis virus ns4a protein increases its virulence in mice, but not its growth rate in vitro.our previous studies have shown that the japanese encephalitis virus (jev) strain mie/40/2004 is the most virulent of the strains isolated by us in japan from 2002 to 2004. comparison of the amino acid sequence of mie/40/2004 with those of low-virulence strains revealed that an isoleucine residue at position 3 of the mie/40/2004 ns4a protein may increase viral pathogenicity. a recombinant virus with a single valine-to-isoleucine substitution (v3i) at position 3 in the low-virulence mie/41/2002 b ...201121411676
detection of sequences from a potentially novel strain of cell fusing agent virus in mexican stegomyia (aedes) aegypti mosquitoes.flaviviruses (fvs) are a very heterogeneous group of viruses that includes viruses capable of infecting insects and/or vertebrates. different human-disease-causing fvs are disseminated by mosquitoes, and therefore, the search for fv in these insects has recently been proposed in order to evaluate their potential transmission in a given community. an entomological survey was carried out in colima (the hyperendemic dengue fever transmission zone in mexico) to collect culicidae in urban and wild ar ...201121409444
evaluation of envelope domain iii-based single chimeric tetravalent antigen and monovalent antigen mixtures for the detection of anti-dengue antibodies in human sera.flavivirus cross-reactive antibodies in human sera interfere with the definitive identification of dengue virus (denv) infections especially in areas with multiple co-circulating flaviviruses. use of denv envelope domain-iii (ediii) can partially resolve the problem. this study has examined the effect of (i) incorporating the ediiis of four denv serotypes into a single chimeric antigen, and (ii) immobilizing the antigen through specific interaction on the sensitivity and specificity of anti-denv ...201121401963
impaired interferon signaling in dendritic cells from older donors infected in vitro with west nile virus.west nile virus (wnv), a mosquito-borne, single-stranded rna flavivirus, causes significant human morbidity and mortality in the older population; thus, we investigated the effects of aging on infection with wnv in dendritic cells (dcs). we infected dcs with wnv in vitro and quantified cytokines and chemokines (type i ifn and cxcl10), pathogen recognition receptors rig-i, and toll-like receptors 3 and 7. the production of type i ifn was significantly lower in dcs from older donors, compared with ...201121398396
a west nile virus dna vaccine utilizing a modified promoter induces neutralizing antibody in younger and older healthy adults in a phase i clinical trial.west nile virus (wnv) is a flavivirus that causes meningitis and encephalitis. there are no licensed vaccines to prevent wnv in humans. the safety and immunogenicity of a first-generation wnv dna vaccine was demonstrated in a clinical trial and a similar dna vaccine has been licensed for use in horses.201121398392
partial maturation: an immune-evasion strategy of dengue virus?cleavage of the precursor membrane (prm) protein is required for the activation of flavivirus infectivity. however, many studies have shown that, for dengue virus in particular, prm cleavage and maturation is inefficient. heterogeneity of wild-type dengue virus preparations with regard to the presence of uncleaved prm in the virion is mirrored in the substantial levels of prm-specific antibodies that are produced following dengue infection. what might be the evolutionary advantage for the virus ...201121388812
Displaying items 101 - 200 of 3318