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elevated soluble cd163 plasma levels are associated with disease severity in patients with hemorrhagic fever with renal syndrome.hantaan virus is a major zoonotic pathogen that causesing hemorrhagic fever with renal syndrome (hfrs). although hfrs pathogenesis has not been entirely elucidated, the importance of host-related immune responses in hfrs pathogenesis has been widely recognized. cd163, a monocyte and macrophage-specific scavenger receptor that plays a vital function in the hosts can reduce inflammation, is shed during activation as soluble cd163 (scd163). the aim of this study was to investigate the pathological ...201425392926
a phase 1 clinical trial of hantaan virus and puumala virus m-segment dna vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation.haemorrhagic fever with renal syndrome (hfrs) is endemic in asia, europe and scandinavia, and is caused by infection with the hantaviruses hantaan (htnv), seoul (seov), puumala (puuv), or dobrava (dobv) viruses. we developed candidate dna vaccines for hfrs expressing the gn and gc genes of htnv or puuv and evaluated them in an open-label, single-centre phase 1 study. three groups of nine participants each were vaccinated on days 0, 28 and 56 with the dna vaccines for htnv, puuv, or a mixture of ...201424447183
discovery of hantaviruses and of the hantavirus genus: personal and historical perspectives of the presidents of the international society of hantaviruses.we three authors, the two past presidents (hwl and av) and the current president (css) of the international society for hantaviruses (ish) have attended most of the nine international conferences on hfrs, hps and hantaviruses (table 1). these conferences have provided a forum for a synergistic group of clinicians, basic researchers, mammalogists, epidemiologists and ecologists to share their expertise and interests in all aspects of hantavirus research. much of what is now hantavirus dogma was o ...201424412711
dna vaccines for hfrs: laboratory and clinical studies.dna vaccines can be constructed to produce specific immunogens while avoiding the risks associated with propagating infectious viruses. plasmid dna vaccines have well established manufacturing procedures and are safe in that they are replication defective, cannot revert to virulence and cannot be transmitted from person-to-person or into the environment. in addition, dna vaccines can be combined to form multivalent formulations and can be delivered by a variety of methods. because of these numer ...201424370868
neutrophil depletion suppresses pulmonary vascular hyperpermeability and occurrence of pulmonary edema caused by hantavirus infection in c.b-17 scid mice.hantavirus infections are characterized by vascular hyperpermeability and neutrophilia. however, the pathogenesis of this disease is poorly understood. here, we demonstrate for the first time that pulmonary vascular permeability is increased by hantaan virus infection and results in the development of pulmonary edema in c.b-17 severe combined immunodeficiency (scid) mice lacking functional t cells and b cells. increases in neutrophils in the lung and blood were observed when pulmonary edema bega ...201424719427
the role of mites in the transmission and maintenance of hantaan virus (hantavirus: bunyaviridae).this review examines the evidence indicating a role for parasitic mites in the transmission and maintenance of hantaan virus in nature. the available data, much of it from recent studies in china, indicate that both trombiculid and gamasid mites are naturally infected with hantaan virus and that infected mites can transmit the virus by bite to laboratory mice and transovarially (vertically) through eggs to their offspring. collectively, these findings challenge the current paradigm of hantavirus ...201424958909
involvement of the akt/nf-κb pathways in the htnv-mediated increase of il-6, ccl5, icam-1, and vcam-1 in huvecs.hantaan virus (htnv) infection causes a severe form of hfrs(hemorrhagic fever with renal syndrome)in asia. although htnv has been isolated for nearly forty years, the pathogenesis of hfrs is still unknown, and little is known regarding the signaling pathway that is activated by the virus.201424714064
recent evidence of hantavirus circulation in the american tropic.hantaan virus was discovered in korea during the 1970s while other similar viruses were later reported in asia and europe. there was no information about hantavirus human infection in the americas until 1993 when an outbreak was described in the united states. this event promoted new studies to find hantaviruses in the americas. at first, many studies were conducted in brazil, argentina, chile, uruguay and paraguay, while other latin american countries began to report the presence of these agent ...201424638203
changes in diversification patterns and signatures of selection during the evolution of murinae-associated hantaviruses.in the last 50 years, hantaviruses have significantly affected public health worldwide, but the exact extent of the distribution of hantavirus diseases, species and lineages and the risk of their emergence into new geographic areas are still poorly known. in particular, the determinants of molecular evolution of hantaviruses circulating in different geographical areas or different host species are poorly documented. yet, this understanding is essential for the establishment of more accurate scen ...201424618811
induction of specific humoral and cellular immune responses in a mouse model following gene fusion of hsp70c and hantaan virus gn and s0.7 in an adenoviral vector.heat shock proteins (hsps) display adjuvant functions when given as fusion proteins to enhance vaccination efficiency. to evaluate enhanced potency of hantaan virus (htnv) glycoprotein (gp) and nucleocapsid protein (np) immunogenicity by heat shock protein 70 (hsp70), a recombinant adenovirus rad-gns0.7-pcag-hsp70c expression vector was developed by genetically linking the hsp70 c-terminal gene (hsp70 359-610 aa, hsp70c) to the gn and 0.7 kb fragment of the np (aa1-274-s0.7). c57bl/6 mice were i ...201424505421
analysis of an outbreak of hemorrhagic fever with renal syndrome in college students in xi'an, china.the aim of the present study was to analyze an outbreak of hemorrhagic fever with renal syndrome (hfrs), caused by a hantavirus, in college students in the northern urban area of xi'an in 2012. the outbreak affected six students and included two deaths. the epidemiological survey revealed that both of the deceased cases were misdiagnosed initially, and treatment was delayed. furthermore, a higher rodent population density and lower hfrs vaccine coverage were observed in the affected area, which ...201424481251
hantaan virus infection induces cxcl10 expression through tlr3, rig-i, and mda-5 pathways correlated with the disease severity.hantaan virus (htnv) is a major agent causing hemorrhagic fever with renal syndrome (hfrs). although the pathogenesis of hfrs is unclear, some reports have suggested that the abundant production of proinflammatory cytokines and uncontrolled inflammatory responses may contribute to the development of hfrs. cxcl10 is one of these cytokines and is found to be involved in the pathogenesis of many virus infectious diseases. however, the role of cxcl10 in the pathogenesis of hfrs and the molecular reg ...201424701034
transmission of haemorrhagic fever with renal syndrome in china and the role of climate factors: a review.haemorrhagic fever with renal syndrome (hfrs) is a rodent-borne disease that poses a serious public health threat in china. hfrs is caused by hantaviruses, mainly seoul virus in urban areas and hantaan virus in agricultural areas. although preventive measures including vaccination programs and rodent control measures have resulted in a decline in cases in recent years, there has been an increase in incidence in some areas and new endemic areas have emerged. this review summarises the recent lite ...201525704595
il-33/st2 correlates with severity of haemorrhagic fever with renal syndrome and regulates the inflammatory response in hantaan virus-infected endothelial cells.hantaan virus (htnv) causes a severe lethal haemorrhagic fever with renal syndrome (hfrs) in humans. despite a limited understanding of the pathogenesis of hfrs, the importance of the abundant production of pro-inflammatory cytokines has been widely recognized. interleukin 33 (il-33) has been demonstrated to play an important role in physiological and pathological immune responses. after binding to its receptor st2l, il-33 stimulates the th2-type immune response and promotes cytokine production. ...201525658420
concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in sri lanka: implications for a potentially worldwide underestimated problem.two global (re-)emerging zoonoses, leptospirosis and hantavirus infections, are clinically indistinguishable. thirty-one patients, hospitalized in sri lanka for acute severe leptospirosis, were after exclusion of other potentially involved pathogens, prospectively screened with igm elisa for both pathogens. of these, nine (29·0%) were positive for leptospirosis only, one (3·2%) for hantavirus only, seven (22·5%) for both pathogens concomitantly, whereas 13 (41·9%) remained negative for both. mor ...201525582980
influence of hla-drb alleles on haemorrhagic fever with renal syndrome in a chinese han population in hubei province, china.specific human leucocyte antigen (hla) alleles are considered a genetic risk factor for the progression of haemorrhagic fever with renal syndrome (hfrs) caused by hantaviruses. the aim of this study was to establish whether hla-drb alleles are associated with the severity of hfrs caused by different types of hantaviruses in a chinese han population from hubei province of central china. twenty-two specific hla-drb alleles were analysed by sequence-specific primer-polymerase chain reaction (ssp-pc ...201525169964
hantaan virus surveillance targeting small mammals at nightmare range, a high elevation military training area, gyeonggi province, republic of korea.rodent-borne disease surveillance was conducted at nightmare range (nm-r), near the demilitarized zone in northeast gyeonggi province, republic of korea, to identify hemorrhagic fever with renal syndrome (hfrs) risks for a mountainous high-elevation (500 m) military training site. monthly surveys were conducted from january 2008-december 2009. a total of 1,720 small mammals were captured belonging to the orders rodentia [families, sciuridae (1 species) and muridae (7 species)] and soricomorpha [ ...201525874643
nlrp3 inflammasome is responsible for hantavirus inducing interleukin-1β in thp-1 cells.persistent high fever is one typical clinical symptom of hemorrhagic fever with renal syndrome (hfrs) and circulating interleukin-1β (il-1β) is elevated throughout hfrs. the mechanisms responsible for viral induction of il-1β secretion are unknown. in the present study, hantaan virus (htnv) induced the secretion of il-1β in the human monocytic cell line thp-1. induction of il-1β by htnv relies on the activation of caspase-1. small hairpin rna knockdown in htnv-infected thp-1 cells indicated that ...201525847326
hantaan virus can infect human keratinocytes and activate an interferon response through the nuclear translocation of irf-3.hantaan virus (htnv) is a rodent-borne virus that causes hemorrhagic fever with renal syndrome (hfrs) in asia and can be transmitted to humans through bites or the inhalation of aerosolized urine, droppings, or saliva of infected rodents. keratinocytes predominate in the epidermis and reportedly serve as a replication site for multiple vector-borne viruses, little is known about the susceptibility of human skin cells to htnv infection. therefore, we aimed to evaluate whether human keratinocytes ...201525461845
bilateral simultaneous angle-closure glaucoma associated with septic condition of korean hemorrhagic fever (khf).to report a case of bilateral simultaneous angle-closure glaucoma caused by septic condition of korean hemorrhagic fever.201523429623
hantavirus infections.over the past few decades understanding and recognition of hantavirus infection has greatly improved worldwide, but both the amplitude and the magnitude of hantavirus outbreaks have been increasing. several novel hantaviruses with unknown pathogenic potential have been identified in a variety of insectivore hosts. with the new hosts, new geographical distributions of hantaviruses have also been discovered and several new species were found in africa. hantavirus infection in humans can result in ...201524750436
phosphorylation of the nucleocapsid protein of hantaan virus by casein kinase ii.hantaanvirus (htnv) is the prototype of the genus hantavirus, which belongs to the family bunyaviridae. hantaviruses are carried and transmitted by rodents and are known to cause two serious disease syndromes in humans i.e., hemorrhagic fever with renal syndrome (hfrs) and the hantavirus pulmonary syndrome (hps). htnv is an enveloped virus that contains a tripartite genome consisting of three negative-sense rna segments (l, m, s), and the s and m segment of htnv, respectively, encode the viral n ...201525935306
hantaan virus infection induces both th1 and thgranzyme b+ cell immune responses that associated with viral control and clinical outcome in humans.hantaviruses infection causing severe emerging diseases with high mortality rates in humans has become public health concern globally. the potential roles of cd4(+)t cells in viral control have been extensively studied. however, the contribution of cd4(+)t cells to the host response against hantaan virus (htnv) infection remains unclear. here, based on the t-cell epitopes mapped on htnv glycoprotein, we studied the effects and characteristics of cd4(+)t-cell responses in determining the outcome ...201525836633
changes in rodent abundance and weather conditions potentially drive hemorrhagic fever with renal syndrome outbreaks in xi'an, china, 2005-2012.increased risks for hemorrhagic fever with renal syndrome (hfrs) caused by hantaan virus have been observed since 2005, in xi'an, china. despite increased vigilance and preparedness, hfrs outbreaks in 2010, 2011, and 2012 were larger than ever, with a total of 3,938 confirmed hfrs cases and 88 deaths in 2010 and 2011.201525822936
soluble scavenger receptor cd163 is associated with severe acute kidney injury in patients with hantaan virus infection.cd163, a hemoglobin scavenger receptor for haptoglobin-hemoglobin complexes, is expressed by monocytes/macrophages and is often shed as soluble cd163 (scd163) in response to inflammatory stimuli. this scavenger receptor is reported to dampen the inflammatory response, and high plasma levels of scd163, which are thought to reflect the total level of cd163 expression, may predict the severity of disease. to understand the role of scd163 in the pathogenesis of hemorrhagic fever with renal syndrome ...201525789628
kinetics and immunodominance of virus-specific t cell responses during hantaan virus infection.immunodominant t cell responses are important for protection against virus challenge. however, studies screening for the immunodominant t cell responses and following their kinetics in acute hantaan virus (htnv) infection are very limited. herein, the htnv nucleocapsid protein-specific t cell responses were longitudinally screened in 15 patients with acute htnv infection, eight of whom had a particularly severe hemorrhagic fever with renal syndrome (hfrs). an extremely impaired ifn-γ-producing t ...201525945718
development of reverse transcription loop-mediated isothermal amplification assays to detect hantaan virus and seoul virus.we developed two assays based on one-step reverse transcription loop-mediated isothermal amplification (rt-lamp) to identify hantaan virus (htnv) and seoul virus (seov), members of the hantavirus genus that cause hemorrhagic fever with renal syndrome (hfrs). our results showed that these assays can be conducted within 30min under isothermal conditions. the detection limit for htnv was around 10 copies per reaction, similar to detection levels for quantitative reverse transcription polymerase cha ...201525920565
effects of different doses of nucleocapsid protein from hantaan virus a9 strain on regulation of interferon signaling.hantaan virus a9 strain (htnv a9) is an etiologic agent of hemorrhagic fever with renal syndrome in china. the virulence of the pathogenic hantaviruses is determined by their ability to alter key signaling pathways of early interferon (ifn) induction within cells. the potential role of htnv a9 structural proteins, such as nucleocapsid (n) and envelope glycoproteins (gn and gc), in regulating human's innate antiviral immune response has not yet been clarified. in this study, we investigated the e ...201526196448
cd8low cd100- t cells identify a novel cd8 t cell subset associated with viral control during human hantaan virus infection.hantaan virus (htnv) infection can cause a severe lethal hemorrhagic fever with renal syndrome (hfrs) in humans. cd8(+) t cells play a critical role in combating htnv infections. however, the contributions of different cd8(+) t cell subsets to the immune response against viral infection are poorly understood. here, we identified a novel subset of cd8(+) t cells characterized by the cd8(low) cd100(-) phenotype in hfrs patients. the cd8(low) cd100(-) subset accounted for a median of 14.3% of the t ...201526378166
elevated plasma soluble cd14 levels correlate with the monocyte response status during hantaan virus infection in humans.hantaan virus (htnv) infection can cause severe hemorrhagic fever with renal syndrome (hfrs) in humans. cd14, a pattern recognition receptor recognizing lipopolysaccharide, is highly expressed on monocytes and can be shed as soluble cd14 (scd14) upon monocyte activation. to understand the role of scd14 in hfrs, the scd14 plasma concentrations from 45 hfrs patients were quantified, and the relationships between the plasma scd14 level and the monocyte response status and clinical parameters were a ...201526196589
hemorrhagic fever with renal syndrome: pathogenesis and clinical picture.hantaan virus (htnv) causes hemorrhagic fever with renal syndrome (hfrs), which is a zoonosis endemic in eastern asia, especially in china. the reservoir host of htnv is field mouse (apodemus agraricus). the main manifestation of hfrs, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. in this paper, we review the current knowledge of the pathogenesis of hfrs including virus factor, immunity factor and host genetic factors. furthermore, the treatment a ...201626870699
prevalence of hemorrhagic fever with renal syndrome in yiyuan county, china, 2005-2014.hemorrhagic fever with renal syndrome (hfrs) is highly endemic in mainland china, where human cases account for 90 % of the total global cases. yiyuan county is one of the most serious affected areas in china. therefore, there is an urgent need for monitoring and predicting hfrs incidence in yiyuan to make the control of hfrs more effective.201626852019
long-term immunogenicity and safety of inactivated hantaan virus vaccine (hantavax™) in healthy adults.hemorrhagic fever with renal syndrome is a serious health problem in eurasian countries, including korea and china. this study evaluated the long-term immunogenicity and safety of formalin-inactivated hantaan virus vaccine (hantavax™).201626826547
hemorrhagic fever with renal syndrome, zibo city, china, 2006-2014.analysis of hemorrhagic fever with renal syndrome cases in zibo city, china, during 2006-2014 showed that it occurred year-round. peaks in spring and fall/winter were caused by hantaan and seoul viruses, respectively. rodent hosts were the striped field mouse for hantaan virus and the brown rat and house mouse for seoul virus.201626812444
cytokine response to hantaan virus infection in patients with hemorrhagic fever with renal syndrome.hantaan virus (htnv) infection of the human body causes a severe acute infectious disease known as hemorrhagic fever renal syndrome (hfrs). the aim of this study was to correlate patient cytokine profiles to hfrs severity. in this study, we discuss the clinical significance of evaluating hfrs treatment outcomes using cytokine information. the levels of 18 cytokines were quantitatively determined in three groups: 34 htnv igm+ cases, 63 htnv igm- negative cases, and 78 healthy volunteers. the leve ...201627943332
phylogeographic analysis of hemorrhagic fever with renal syndrome patients using multiplex pcr-based next generation sequencing.emerging and re-emerging infectious diseases caused by rna viruses pose a critical public health threat. next generation sequencing (ngs) is a powerful technology to define genomic sequences of the viruses. of particular interest is the use of whole genome sequencing (wgs) to perform phylogeographic analysis, that allows the detection and tracking of the emergence of viral infections. hantaviruses, bunyaviridae, cause hemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome ...201627221218
genetic characterization of hantaviruses isolated from rodents in the port cities of heilongjiang, china, in 2014.hantavirus is a tripartite negative-sense rna virus. it can infect humans through contaminated rodent excreta and causes two types of fatal human diseases: hemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). china exhibits the highest hfrs occurrence rate in the world, and the heilongjiang area is one of the most severely infected regions.201627038799
a case of a male presenting with fever, parotitis, epididymo-orchitis, and kidney injury. 201627012169
specific interference shrna-expressing plasmids inhibit hantaan virus infection in vitro and in vivo.to investigate the antiviral effects of vectors expressing specific short hairpin rnas (shrnas) against hantaan virus (htnv) infection in vitro and in vivo.201626972493
prevalence of hemorrhagic fever with renal syndrome in qingdao city, china, 2010-2014.hemorrhagic fever with renal syndrome (hfrs) was considered to be transmitted by apodemus agrarius and rattus norvegicus, the principal animal hosts of hantaan virus and seoul virus, respectively. the aim of this study is to determine the correlation of hfrs incidence with capture rate and hantavirus infection rate of rodent species in qingdao city, china. we collected hfrs patients' information and captured field and residential rodents in qingdao city, china from 2010 to 2014. the correlations ...201627786303
mechanistic insight into bunyavirus-induced membrane fusion from structure-function analyses of the hantavirus envelope glycoprotein gc.hantaviruses are zoonotic viruses transmitted to humans by persistently infected rodents, giving rise to serious outbreaks of hemorrhagic fever with renal syndrome (hfrs) or of hantavirus pulmonary syndrome (hps), depending on the virus, which are associated with high case fatality rates. there is only limited knowledge about the organization of the viral particles and in particular, about the hantavirus membrane fusion glycoprotein gc, the function of which is essential for virus entry. we desc ...201627783711
[pathomorphism of hantavirus infection under prolonged heat stress].to provide the morphological characteristics of experimental hantavirus infection under heat stress conditions to identify the possibilities of its modeling in resistant laboratory animals.201628139601
interferon-induced transmembrane protein 3 inhibits hantaan virus infection, and its single nucleotide polymorphism rs12252 influences the severity of hemorrhagic fever with renal syndrome.hantaan virus (htnv) causes hemorrhagic fever with renal syndrome (hfrs). previous studies have identified interferon-induced transmembrane proteins (ifitms) as an interferon-stimulated gene family. however, the role of ifitms in htnv infection is unclear. in this study, we observed that ifitm3 single nucleotide polymorphisms (snp) rs12252 c allele and cc genotype associated with the disease severity and htnv load in the plasma of hfrs patients. in vitro experiments showed that the truncated pro ...201628096800
incorporation of gm-csf or cd40l enhances the immunogenicity of hantaan virus-like particles.a safe and effective hantaan virus (htnv) vaccine is highly desirable because htnv causes an acute and often fatal disease (hemorrhagic fever with renal syndrome, hfrs). since the immunity of the inactivated vaccine is weak and the safety is poor, htnv virus-like particles (vlps) offer an attractive and safe alternative. these particles lack the viral genome but are perceived by the immune system as virus particles. we hypothesized that adding immunostimulatory signals to vlps would enhance thei ...201628066721
corrigendum: hemorrhagic fever with renal syndrome: pathogenesis and clinical picture.[this corrects the article on p. 1 in vol. 6, pmid: 26870699.].201627981038
structure and function of hla-a*02-restricted hantaan virus cytotoxic t-cell epitope that mediates effective protective responses in hla-a2.1/k(b) transgenic mice.hantavirus infections cause severe emerging diseases in humans and are associated with high mortality rates; therefore, they have become a global public health concern. our previous study showed that the cd8(+) t-cell epitope aa129-aa137 (fvvpillka, fa9) of the hantaan virus (htnv) nucleoprotein (np), restricted by human leukocyte antigen (hla)-a*02, induced specific cd8(+) t-cell responses that controlled htnv infection in humans. however, the in vivo immunogenicity of peptide fa9 and the effec ...201627551282
construction and immunological characterization of cd40l or gm-csf incorporated hantaan virus like particle.infection of hantaan virus (htnv) usually causes hemorrhagic fever with renal syndrome (hfrs). china has the worst epidemic incidence of hfrs as well as high fatality. inactivated whole virus has been used for hfrs vaccination, however there are still problems such as safety concerns. cd40 ligand (cd40l) and granulocyte macrophage colony-stimulating factor (gm-csf) are well-known immune stimulating molecules that can enhance antigen presenting, lymphocytes activation and maturation, incorporatio ...201627542281
development of a sybr-green ⅰ quantitative pcr assay for the detection and genotyping of different hantaviruses.hemorrhagic fever with renal syndrome (hfrs) is a severe, viral zoonotic disease which occurs worldwide, particularly in asia and europe. in china, the hantaan virus (htnv) and the seoul virus (seov) are known to be the most prevalent causative agents of hfrs. since no protective vaccines or effective treatments are available for human use, accurate and reliable diagnostic methods are essential for disease surveillance. in the present study, the viral loads in cell culture supernatant, infected ...201627430149
genetic diversity and reassortment of hantaan virus tripartite rna genomes in nature, the republic of korea.hantaan virus (htnv), a negative sense tripartite rna virus of the family bunyaviridae, is the most prevalent hantavirus in the republic of korea (rok). it is the causative agent of hemorrhagic fever with renal syndrome (hfrs) in humans and maintained in the striped field mouse, apodemus agrarius, the primary zoonotic host. clinical hfrs cases have been reported commonly in hfrs-endemic areas of gyeonggi province. recently, the death of a member of the rok military from gangwon province due to h ...201627315053
the assessment of hantaan virus-specific antibody responses after the immunization program for hemorrhagic fever with renal syndrome in northwest china.xianyang city is one of the main hemorrhagic fever with renal syndrome (hfrs) epidemic areas in northwest china. although the hfrs immunity program has been provided in this city, hfrs is still occurred every year. in order to implement the vaccination program effectively and to control hfrs, the analysis of antibody responses specific to hantaan virus (htnv) in individuals after vaccination is essential. in this study, a total of 100 subjects were divided into 5 groups: unvaccinated, 1, 3, 29 a ...201627824286
comparative structural and functional analysis of bunyavirus and arenavirus cap-snatching endonucleases.segmented negative strand rna viruses of the arena-, bunya- and orthomyxovirus families uniquely carry out viral mrna transcription by the cap-snatching mechanism. this involves cleavage of host mrnas close to their capped 5' end by an endonuclease (en) domain located in the n-terminal region of the viral polymerase. we present the structure of the cap-snatching en of hantaan virus, a bunyavirus belonging to hantavirus genus. hantaan en has an active site configuration, including a metal co-ordi ...201627304209
the experimental research (in vitro) of carrageenans and fucoidans to decrease activity of hantavirus.the effect of carrageenans and fucoidans on the activity of hantavirus is studied. it has been found that among carrageenans a significant antiviral effect is exerted by the ι-type, which decreases the viral titer by 2.5 log focus forming units per ml; among fucoidans, by a preparation from laminaria cichorioides, which reduces the number of infected cells from 27.0 to 5.3 after pretreatment of both the macrophage culture and hantavirus. the antiviral effect of fucoidan from laminaria japonica i ...201626943130
detection of hantaan virus rna from anti-hantaan virus igg seronegative rodents in an area of high endemicity in republic of korea.hantaan virus (htnv), of the family bunyaviridae, causes hemorrhagic fever with renal syndrome (hfrs) in humans. although the majority of epidemiologic studies have found that rodents are seropositive for hantavirus-specific immunoglobulin, the discovery of hantavirus rna in seronegative hosts has led to an investigation of the presence of htnv rna in rodents captured in hfrs endemic areas. htnv rna was detected in seven (3.8%) of 186 anti-htnv igg seronegative rodents in republic of korea (rok) ...201626917012
the andes virus nucleocapsid protein directs basal endothelial cell permeability by activating rhoa.andes virus (andv) predominantly infects microvascular endothelial cells (mecs) and nonlytically causes an acute pulmonary edema termed hantavirus pulmonary syndrome (hps). in hps patients, virtually every pulmonary mec is infected, mecs are enlarged, and infection results in vascular leakage and highly lethal pulmonary edema. we observed that mecs infected with the andv hantavirus or expressing the andv nucleocapsid (n) protein showed increased size and permeability by activating the rheb and r ...201627795403
[coordination of the changes in some sites of the hantaviral segments].correlation in the changes of the nucleotide and amino acid sequences at the hantaan virus occurring in different parts of s- and m-segments were studied. the correlation was analyzed using comparison of substitutions in aligned nucleic sequences of the segments. correlations of the nucleotide substitutions between s- and m-segments were observed. probably, this coordination of the changes in both segments reflects features of the tertiary structure of rna.201623012982
ckd and infectious diseases in asia pacific: challenges and opportunities.the exact number of patients with chronic kidney disease (ckd) in asia pacific is uncertain. in numeric terms, the region is home to the largest population of patients with untreated chronic kidney failure. the climatic, geographic, social, cultural, economic, and environmental diversity within this region is higher than in any other part of the world. large parts of the region face a climate-related burden of infectious diseases. infections contribute to the development and progression of ckd a ...201626943982
screening and identification of an h-2k(b)-restricted ctl epitope within the glycoprotein of hantaan virus.the cytotoxic t lymphocyte (ctl) response plays a key role in controlling viral infection, but only a few epitopes within the htnv glycoprotein (gp) that are recognized by ctls have been reported. in this study, we identified one murine htnv gp-derived h2-k(b)-restricted ctl epitope in c57bl/6 mice, which could be used to design preclinical studies of vaccines for htnv infection. first, 15 8-mer peptides were selected from the htnv gp amino acid sequence based on a percentile rank of <=1% by ied ...201627933274
htnv-induced upregulation of mir-146a in huvecs promotes viral infection by modulating pro-inflammatory cytokine release.increasing research has shown a link between viruses and mirnas, such as mirna-146a, in regulating virus infection and replication. in the current study, the association between mir-146a and hantaan virus (htnv) infection in human umbilical vein endothelial cells (huvecs) was investigated, with a focus on examining the expression of pro-inflammatory cytokines. the results showed that htnv infection promoted the production of mir-146a in huvecs and activated nf-κb(nuclear factor-κb) signaling, al ...201728843856
elevated plasma growth arrest-specific 6 protein levels are associated with the severity of disease during hantaan virus infection in humans.hemorrhagic fever with renal syndrome (hfrs) is caused by hantaan virus (htnv) and seoul virus infection in asia. the clinical manifestation of hfrs is characterized by the rapid loss of renal function (acute kidney injury) and thrombocytopenia. the specific immune mechanisms that cause thrombocytopenia in hfrs are not well described. the growth arrest-specific 6 (gas6) protein and tam (tyro3, axl and mer) receptors have been recently shown to play prominent roles in immune regulation, and high ...201728537534
in-cell western assays to evaluate hantaan virus replication as a novel approach to screen antiviral molecules and detect neutralizing antibody titers.hantaviruses encompass rodent-borne zoonotic pathogens that cause severe hemorrhagic fever disease with high mortality rates in humans. detection of infectious virus titer lays a solid foundation for virology and immunology researches. canonical methods to assess viral titers rely on visible cytopathic effects (cpe), but hantaan virus (htnv, the prototype hantavirus) maintains a relatively sluggish life cycle and does not produce cpe in cell culture. here, an in-cell western (icw) assay was util ...201728676847
hemorrhagic fever with renal syndrome caused by hantaan virus infection in four pregnant chinese women.hantavirus infection during pregnancy can influence both maternal and fetal outcomes. here, we describe four cases of hemorrhagic fever with renal syndrome (hfrs) in pregnant chinese women. the hfrs put these women at increased risk for severe illness, despite the patients' symptomologies in the onset phase were similar to those observed in non-pregnant hfrs patients, such as fever, headache, nausea, and thrombocytopenia. pregnant women appeared to have a more severe status, presenting with seve ...201728504470
hantavirus surveillance and genetic diversity targeting small mammals at camp humphreys, a us military installation and new expansion site, republic of korea.small mammal surveillance was conducted (2008-2010, 2012) at camp (cp) humphreys, a us army installation and new expansion site, republic of korea (rok), to identify hemorrhagic fever with renal syndrome health threats to us military/civilian populations during its ongoing expansion phase. small mammals were collected using sherman live capture traps and transported to korea university where they were euthanized, tissues removed, and assayed to determine hantavirus igg antibody-positive and hant ...201728448595
[recombinant expression of hantaan virus protein n with application of western-blot in detecting anti-hantavirus antibody].objective: s gene of hantavirus(hv) was expressed in insect cells by genetic engineering technology. the expression product of s gene was used as antigen to detect anti-hv specific antibody igg in serum. methods: gene encoding np of the strain hv-z10 was amplified by pcr and then its eukaryotic expression system rbac-z10s-tn was constructed by using the routine genetic engineering method. sds-page was applied to measure the expression of rnp.ion-exchange plus ni-nta-affinity chromatography was p ...201728468076
meteorological factors affect the epidemiology of hemorrhagic fever with renal syndrome via altering the breeding and hantavirus-carrying states of rodents and mites: a 9 years' longitudinal study.the incidence of hemorrhagic fever with renal syndrome (hfrs) in qingdao, china was three times higher than that of the average national level. here we characterized the epidemiology, ecological determinants and pathogen evolution of hfrs in qingdao during 2007-2015. in this longitudinal study, a total of 1846 hfrs patients and 41 hfrs-related deaths were reported. hfrs in qingdao peaked once a year in the fourth quarter. we built a time series generalized additive model, and found that meteorol ...201729184158
structural transitions of the conserved and metastable hantaviral glycoprotein envelope.hantaviruses are zoonotic pathogens with a near-global distribution that can cause severe hemorrhagic fever and pulmonary syndrome. the outer membrane of the hantavirus envelope displays a lattice of two glycoproteins, gn and gc, which orchestrate host cell recognition and entry. here, we describe the crystal structure of the gn glycoprotein ectodomain from the asiatic hantaan virus (htnv), the most prevalent pathogenic hantavirus. structural overlay analysis reveals that the htnv gn fold is hig ...201728835498
becoming an international scientist in south korea: ho wang lee's research activity about epidemic hemorrhagic fever.in the 1960-70s, south korea was still in the position of a science latecomer. although the scientific research environment in south korea at that time was insufficient, there was a scientist who achieved outcomes that could be recognized internationally while acting in south korea. he was ho wang lee(1928~ ) who found hantann virus that causes epidemic hemorrhagic fever for the first time in the world. it became a clue to identify causative viruses of hemorrhagic diseases that were scattered he ...201728814703
interannual cycles of hantaan virus outbreaks at the human-animal interface in central china are controlled by temperature and rainfall.hantavirus, a rodent-borne zoonotic pathogen, has a global distribution with 200,000 human infections diagnosed annually. in recent decades, repeated outbreaks of hantavirus infections have been reported in eurasia and america. these outbreaks have led to public concern and an interest in understanding the underlying biological mechanisms. here, we propose a climate-animal-hantaan virus (htnv) infection model to address this issue, using a unique dataset spanning a 54-y period (1960-2013). this ...201728696305
hantavirus rna prevalence in myomorph rodents on bolshoy ussuriysky island at the sino-russian border.to understand the distribution and infection status of hantavirus in myomorph rodents on bolshoy ussuriysky island (heixiazi island) at the sino-russian border, and to provide data for the safe development and utilization of bolshoy ussuriysky island.201728678679
prediction of b cell epitopes among hantavirus strains causing hemorragic fever with renal syndrome.hantavirus infections are now recognized to be a global problem. the hantaviruses include several genotypic variants of the virus with different distributions in varying geographical regions. the virus genotypes seem to segregate in association with certain manifestations specific for each syndrome. they primarily include hfrs, hcps, febrile illness with or without mild involvement of renal diseases. in the course of our study on hantavirus etiology of febrile illnesses, we recovered a hantaviru ...201727748540
antiviral therapy and prevention against hantavirus infections.hantaviruses are emerging zoonoses hosted by small mammals. in humans, they cause two diseases. hemorrhagic fever with renal syndrome is mainly caused by dobrava-belgrade virus, puumala virus, seoul virus and hantaan virus in asia and europe. on the other hand, the most important causes of hantavirus cardiopulmonary syndrome are sin nombre virus and andes virus in americas. ribavirin yet remains the only licensed drug against the hantavirus infections, but its sufficient antiviral activity remai ...201728105849
the long noncoding rna neat1 exerts anti-hantaviral effects by acting as a positive feedback for rig-i signaling.hantavirus infection, which causes zoonotic diseases with a high mortality rate in humans, has long been a global public health concern. over the past decades, accumulating evidence suggests that long noncoding rnas (lncrnas) play key regulatory roles in innate immunity. however, the involvement of host lncrnas in hantaviral control remains uncharacterized. in this study, we identified the lncrna, neat1, as a vital antiviral modulator. neat1 was dramatically upregulated after hantaan virus (htnv ...201728202761
anthropogenically driven environmental changes shift the ecological dynamics of hemorrhagic fever with renal syndrome.zoonoses are increasingly recognized as an important burden on global public health in the 21st century. high-resolution, long-term field studies are critical for assessing both the baseline and future risk scenarios in a world of rapid changes. we have used a three-decade-long field study on hantavirus, a rodent-borne zoonotic pathogen distributed worldwide, coupled with epidemiological data from an endemic area of china, and show that the shift in the ecological dynamics of hantaan virus was c ...201728141833
detection of imjin virus and seoul virus in crocidurine shrews in shandong province, china.recently, hantaviruses have been discovered in insectivores in europe, asia, africa, and north america. imjin virus (mjnv) was first isolated from the lung tissues of ussuri white-toothed shrew (crocidura lasiura) from south korea in 2009. we aim to detect the species and prevalence of insectivore- and rodent-borne hantaviruses in shrews and rodents.201728287930
type inactivated bivalent hantavirus vaccines using dual fluorescence quantitative real-time pcr: establishment and evaluation.to establish a dual fluorescence quantitative real-time polymerase chain reaction (dfqrt-pcr) method for typing inactivated bivalent vaccines of hantaan virus (htnv, type i) and seoul virus (seov, type ii) found in china. primers and probes were designed based on s segment of the hantavirus. fam and hex were added to the probes for the type i and type ii vaccines, respectively. the s fragments were cloned into the pmd18-t vector to create pmd18-t/htnv and pmd18-t/seov plasmids, respectively. the ...201727301695
insufficient efficacy and safety of intravenous ribavirin in treatment of haemorrhagic fever with renal syndrome caused by puumala virus.intravenous ribavirin has been reported to be an effective treatment for haemorrhagic fever with renal syndrome (hfrs) caused by hantaan virus in asia. however, its therapeutic benefits for hfrs caused by puumala virus (puuv) in europe are still unknown.201728276794
sequence-independent, single-primer amplification next-generation sequencing of hantaan virus cell culture-based isolates.hantaan virus (htnv), identified in the striped field mouse (apodemus agrarius), belongs to the genus hantavirus of the family bunyaviridae and contains tripartite rna genomes, small (s), medium (m), and large (l) segments. htnv is a major causative for hemorrhagic fever with renal syndrome (hfrs) with fatality rates ranging from 1% to 15% in the republic of korea (rok) and china. defining of htnv whole-genome sequences and isolation of the infectious particle play a critical role in the charact ...201727895275
appearance of renal hemorrhage in adult mice after inoculation of patient-derived hantavirus.hemorrhagic fever with renal syndrome (hfrs) caused by hantavirus infection is characterized by fever, renal dysfunction and hemorrhage. an animal model mimicking symptoms of hfrs remains to be established. in this study, we evaluated the pathogenicity of an hfrs patient-derived hantaan virus (htnv) in adult mice.201728122569
novel identified hla-a*0201-restricted hantaan virus glycoprotein cytotoxic t-cell epitopes could effectively induce protective responses in hla-a2.1/kb transgenic mice may associate with the severity of hemorrhagic fever with renal syndrome.hantaan virus (htnv) infections can cause severe hemorrhagic fever with renal syndrome (hfrs) in humans, which is associated with high fatality rates. cytotoxic t cell (ctl) responses contribute to virus elimination; however, to date, hla class i allele-restricted htnv glycoprotein (gp) epitopes recognized by ctls have not been reported, limiting our understanding of ctl responses against htnv infection in humans. in this study, 34 htnv gp nine-mer epitopes that may bind to hla-a*0201 molecules ...201729312318
hantavirus gc induces long-term immune protection via lamp-targeting dna vaccine strategy.hemorrhagic fever with renal syndrome (hfrs) occurs widely throughout eurasia. unfortunately, there is no effective treatment, and prophylaxis remains the best option against the major pathogenic agent, hantaan virus (htnv), which is an old world hantavirus. however, the absence of cellular immune responses and immunological memory hampers acceptance of the current inactivated hfrs vaccine. previous studies revealed that a lysosome-associated membrane protein 1 (lamp1)-targeting strategy involvi ...201729273568
serological evidence of thailand orthohantavirus or antigenically related virus infection among rodents in a chronic kidney disease of unknown etiology endemic area, girandurukotte, sri lanka.we have reported high seroprevalence to thailand orthohantavirus (thaiv) or thaiv-related orthohantavirus (trhv) among patients with chronic kidney disease of unknown etiology in girandurukotte, sri lanka. thaiv or trhv infection is considered to be transmitted by rodent hosts in this area, but its reservoir rodents have not yet been identified. hence, 116 rodents were captured, and seroprevalences were examined by indirect immunofluorescent antibody assay (immunofluorescence assay [ifa]) using ...201931339833
comparison of targeted next-generation sequencing for whole-genome sequencing of hantaan orthohantavirus in apodemus agrarius lung tissues.orthohantaviruses, negative-sense single-strand tripartite rna viruses, are a global public health threat. in humans, orthohantavirus infection causes hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. whole-genome sequencing of the virus helps in identification and characterization of emerging or re-emerging viruses. next-generation sequencing (ngs) is a potent method to sequence the viral genome, using molecular enrichment methods, from clinical specimens containing ...201931719616
phylogeographic diversity and hybrid zone of hantaan orthohantavirus collected in gangwon province, republic of korea.hantaan orthohantavirus (hantaan virus, htnv), harbored by apodemus agrarius (the striped field mouse), causes hemorrhagic fever with renal syndrome (hfrs) in humans. viral genome-based surveillance at new expansion sites to identify hfrs risks plays a critical role in tracking the infection source of orthohantavirus outbreak. in the republic of korea (rok), most studies demonstrated the serological prevalence and genetic diversity of orthohantaviruses collected from hfrs patients or rodents in ...202033035222
orthohantaviruses infections in humans and rodents in baoji, china.in recent years, hemorrhagic fever with renal syndrome (hfrs) incidence has been becoming a severe public health problem again due to its significant increase in shaanxi province, china. baoji, located in the guanzhong plain in the central part of shaanxi province, has been severely affected by hfrs since its first emergence in 1955. to better understand the epidemiology of orthohantaviruses infection in humans and the causative agents carried by the rodents, the long-term incidence patterns wer ...202033075097
rodent-borne orthohantaviruses in vietnam, madagascar and japan.hantaviruses are harbored by multiple small mammal species in asia, europe, africa, and the americas. to ascertain the geographic distribution and virus-host relationships of rodent-borne hantaviruses in japan, vietnam, myanmar, and madagascar, rnalater™-preserved lung tissues of 981 rodents representing 40 species, collected in 2011-2017, were analyzed for hantavirus rna by rt-pcr. our data showed hantaan orthohantavirus da bie shan strain in the chinese white-bellied rat (niviventer confucianu ...202134372549
a novel genotype of hantaan orthohantavirus harbored by apodemus agrarius chejuensis as a potential etiologic agent of hemorrhagic fever with renal syndrome in republic of korea.orthohantaviruses, causing hemorrhagic fever with renal syndrome (hfrs) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. despite the significant mortality and morbidity, effective antiviral therapeutics for orthohantavirus infections are currently unavailable. this study aimed to investigate the prevalence of hfrs-associated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern republic of korea (rok).202133979351
multiplex pcr-based nanopore sequencing and epidemiological surveillance of hantaan orthohantavirus in apodemus agrarius, republic of korea.whole-genome sequencing of infectious agents enables the identification and characterization of emerging viruses. the minion device is a portable sequencer that allows real-time sequencing in fields or hospitals. hantaan orthohantavirus (hantaan virus, htnv), harbored by apodemus agrarius, causes hemorrhagic fever with renal syndrome (hfrs) and poses a critical public health threat worldwide. in this study, we aimed to evaluate the feasibility of using nanopore sequencing for whole-genome sequen ...202134066592
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