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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
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
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
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 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
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
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
wars, disasters and kidneys.this paper summarizes the impact that wars had on the history of nephrology, both worldwide and in the ghent medical faculty notably on the definition, research and clinical aspects of acute kidney injury. the paper briefly describes the role of 'trench nephritis' as observed both during world war i and ii, supporting the hypothesis that many of the clinical cases could have been due to hantavirus nephropathy. the lessons learned from the experience with crush syndrome first observed in world wa ...201425409904
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
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
co-circulation of hantaan, kenkeme, and khabarovsk hantaviruses in bolshoy ussuriysky island, china.hemorrhagic fever with renal syndrome (hfrs) was first recognized in far eastern asia in the 1930s, and has been highly prevalent in this region ever since. to reveal the molecular epidemiology of hantaviruses in this region, a total of 374 small mammals (eight species of rodents and one species of shrew) were captured in the chinese part of the bolshoy ussuriysky island (heilongjiang province). hantavirus sequences were recovered from three striped field mice (apodemus agrarius), 11 maximowicz' ...201425087879
epidemic characteristics of hemorrhagic fever with renal syndrome in china, 2006-2012.hemorrhagic fever with renal syndrome (hfrs) caused by hantaviruses is a serious public health problem in china. the national notifiable disease surveillance system (nndss) was established online by china cdc in 2004 and rodent surveillance sites were adjusted to 40 sites in 22 provinces in 2005. here we analyzed the surveillance data of both human cases and rodents host during 2006-2012 to examine the epidemic trends of hfrs in recent years in china.201425012160
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
hantaviruses induce antiviral and pro-inflammatory innate immune responses in astrocytic cells and the brain.although hantaviruses are not generally considered neurotropic, neurological complications have been reported occasionally in patients with hemorrhagic fever renal syndrome (hfrs). in this study, we analyzed innate immune responses to hantavirus infection in vitro in human astrocytic cells (a172) and in vivo in suckling icr mice. infection of a172 cells with pathogenic hantaan virus (htnv) or a novel shrew-borne hantavirus, known as imjin virus (mjnv), induced activation of antiviral genes and p ...201424937036
[construction and identification of luciferase and egfp expression vectors containing human ifn-β promoter].to construct a luciferase expression vector (pgl3-ifnb1) and an enhanced green fluorescent protein expression vector (pge3-ifnb1) containing human ifn-β promoter, and verify the promoter activity of ifn-β in a549 cells.201424909279
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
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
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
quantification of hantaan virus with a sybr green i-based one-step qrt-pcr assay.hantaan virus (htnv) is a major zoonotic pathogen that causes hemorrhagic fever with renal syndrome (hfrs) in asia, especially in china. shaanxi province, which is located in northwest of china, is one of the areas in china most severely afflicted with hfrs epidemics annually. this study aims to establish a quantitative rt-pcr (qrt-pcr) assay to detect htnv both in cell culture and clinical serum samples. we established a sybr green i-based one-step qrt-pcr assay that targets the s segment of th ...201324278449
development of a sybr green i based one-step real-time pcr assay for the detection of hantaan virus.hantaan virus (htnv), which belongs to the genus hantavirus, causes hemorrhagic fever with renal syndrome (hfrs) mainly in china. the diagnosis of hfrs depends on clinical manifestations and serological tests. a sybr green i based one-step real-time pcr assay was established in this study to detect htnv. the htnv standard curves were generated by plotting mean cycle threshold (ct) values versus 10-fold serial dilutions of a previous titrated htnv stock over a wide range of concentrations (1×10(7 ...201424269331
ongoing spillover of hantaan and gou hantaviruses from rodents is associated with hemorrhagic fever with renal syndrome (hfrs) in china.longquan city, zhejiang province, china, has been seriously affected by hemorrhagic fever with renal syndrome (hfrs) since the first cases were registered in 1974. to understand the epidemiology and emergence of hfrs in longquan, which may be indicative of large parts of rural china, we studied long-term incidence patterns and performed a molecular epidemiological investigation of the causative hantaviruses in human and rodent populations.201324147168
hantaviruses induce cell type- and viral species-specific host microrna expression signatures.the mechanisms of hantavirus-induced modulation of host cellular immunity remain poorly understood. recently, micrornas (mirnas) have emerged as a class of essential regulators of host immune response genes. to ascertain if differential host mirna expression toward representative hantavirus species correlated with immune response genes, mirna expression profiles were analyzed in human endothelial cells, macrophages and epithelial cells infected with pathogenic and nonpathogenic rodent- and shrew ...201324074584
role of nucleocapsid protein of hantaviruses in intracellular traffic of viral glycoproteins.to understand the role of nucleocapsid protein (np) of hantaviruses in viral assembly, the effect of np on intracellular traffic of viral glycoproteins gn and gc was investigated. double staining of viral and host proteins in hantaan virus (htnv)-infected vero e6 cells showed that gn and gc were localized to cis-golgi, in which virus particles are thought to be formed. when htnv gn and gc were expressed by a plasmid encoding glycoprotein precursor (gpc), which is posttranslationally cleaved into ...201324070985
elevated plasma soluble sema4d/cd100 levels are associated with disease severity in patients of hemorrhagic fever with renal syndrome.hantaan virus (htnv) could cause a severe lethal hemorrhagic fever with renal syndrome (hfrs) in humans. despite a limited understanding of the pathogenesis of hfrs, the importance of host-related immune responses in the pathogenesis of hfrs has been widely recognized. cd100/sema4d has been demonstrated to play an important role in physiological and pathological immune responses, but the functional role of cd100 in infectious diseases has only been inadequately reported. the aim of this study wa ...201324040126
hantaan virus nucleocapsid protein stimulates mdm2-dependent p53 degradation.apoptosis has been shown to be induced and downregulated by the hantaan virus (htnv) nucleocapsid (n) protein. to address these conflicting data, expression of the p53 protein, one of the key molecules involved in apoptosis, was assessed in the presence of the n protein in a549 and hela cells. the amount of p53, increased by drug treatment, was reduced when cells were infected with htnv or transfected with an expression vector of the htnv n protein. when cells were treated with a proteasome inhi ...201323994832
the murine model for hantaan virus-induced lethal disease shows two distinct paths in viral evolutionary trajectory with and without ribavirin treatment.in vitro, ribavirin acts as a lethal mutagen in hantaan virus (htnv)-infected vero e6 cells, resulting in an increased mutation load and viral population extinction. in this study, we asked whether ribavirin treatment in the lethal, suckling mouse model of htnv infection would act similarly. the htnv genomic rna (vrna) copy number and infectious virus were measured in lungs of untreated and ribavirin-treated mice. in untreated, htnv-infected mice, the vrna copy number increased for 10 days posti ...201323903835
[the analysis of hantavirus s gene in apodemus agrarius in changbai area].to gain more insights into epidemiologic characteristics and genotype of hantavirus in apodemus agrarius in changbai area. complete hantavirus s segment sequences were amplified by rt-pcr and sequenced. the phylogenetic trees were constructed for analysis of genetic characters of hantavirus. a total of 58 apodemus agrarius were trapped in the epidemic areas, and complete hantavirus s segment sequences were obtained from 4 lung samples of these rodents (6. 90%0). phylogenetic analysis of the four ...201323895001
clinical and molecular epidemiological features of hemorrhagic fever with renal syndrome in korea over a 10-year period.laboratory diagnosis of hemorrhagic fever with renal syndrome (hfrs), an infectious disease caused by rodent-borne hantaviruses in asia and europe, depends primarily on serological methods. since the advent of such serodiagnostic tests, few reports are available about the clinical and molecular epidemiological features of hfrs.201323871164
spatial analysis of hemorrhagic fever with renal syndrome in zibo city, china, 2009-2012.hemorrhagic fever with renal syndrome (hfrs) is highly endemic in mainland china, where human cases account for 90% of the total global cases. zibo city is one of the most serious affected areas in shandong province china with the hfrs incidence increasing sharply from 2009 to 2012. however, the hotspots of hfrs in zibo remained unclear. thus, a spatial analysis was conducted with the aim to explore the spatial, spatial-temporal and seasonal patterns of hfrs in zibo from 2009 to 2012, and to pro ...201323840719
epidemiology of hantavirus infection in thousand islands regency of jakarta, indonesia.hemorrhagic fever with renal syndrome (hfrs) is a rodent-borne zoonotic disease caused by hantavirus infection. many hfrs cases have been reported in east asia and north europe, while the situation in southeast asia remains unclear. in this study, the prevalence of hantavirus infection in rodents and humans in thousand islands regency, which is close to the port of jakarta, one of the largest historic ports in indonesia, was investigated. a total of 170 rodents were captured in 2005, and 27 (15. ...201323503293
hla-a2 and b35 restricted hantaan virus nucleoprotein cd8+ t-cell epitope-specific immune response correlates with milder disease in hemorrhagic fever with renal syndrome.hantaan virus (htnv) infection in humans is a serious public health concern in asia. a potent t cell activation peptide vaccine from htnv structure protein represents a promising immunotherapy for disease control. however, the t cell epitopes of the htnv restricted by the hla alleles and the role of epitope-specific t cell response after htnv infection remain largely unexplored.201323469304
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
an efficient method for isolation of hantaan virus through serial passages in suckling mice.hantaan virus (htnv) is one of the main etiologic agents for hemorrhagic fever with renal syndrome in china. however, it is very difficult to isolate the virus from its original host, which hampers the viral characterization. this study describes an efficient method for isolating htnv in suckling mice.201323306793
thrombocytopenia as a predictor of severe acute kidney injury in patients with hantaan virus infections.hematological abnormalities often occur several days before kidney injury in patients with hemorrhagic fever with renal syndrome (hfrs). we aimed to investigate the prevalence and prognostic value of the early hematological markers in patients with hfrs caused by hantaan virus (htnv) infection.201323301047
elevated vascular endothelial growth factor levels induce hyperpermeability of endothelial cells in hantavirus infection.to investigate the role of vascular endothelial growth factor (vegf) in haemorrhagic fever with renal syndrome (hfrs).201223206462
the genetic polymorphisms of hla are strongly correlated with the disease severity after hantaan virus infection in the chinese han population.the polymorphism of human leukocyte antigen (hla), which is a genetic factor that influences the progression of hemorrhagic fever with renal syndrome (hfrs) after hantaan virus (htnv) infection, was incompletely understood. in this case-control study, 76 hfrs patients and 370 healthy controls of the chinese han population were typed for the hla-a, -b, and -drb1 loci. the general variation at the hla-drb1 locus was associated with the onset of hfrs (p < 0.05). the increasing frequencies of hla-dr ...201223091554
establishment of sybr green-based qpcr assay for rapid evaluation and quantification for anti-hantaan virus compounds in vitro and in suckling mice.hantaan viruses cause two severe diseases lacking efficient treatment, yet no effective prophylactic vaccines are available. continued exploration of alternative antiviral agents to treat hantavirus-related syndromes remains compulsory. the fluorescence-based quantitative real-time pcr (qpcr) has become the touchstone for target gene quantification. in the present study, standard curves for hantaan virus (htnv), mouse, and human glyceraldehyde-3-phosphate dehydrogenase (gapdh) were generated by ...201323054436
[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
[genetic characteristics of hantaviruses carried by microtus maximowixzii in yakeshi of inner mongolia, china].to analyze the viral genetic characteristics of hantaviruses carried by microtus maximowixzii in yakeshi of inner mongolia autonomous region and its relationship with hantaan virus (htnv) and seoul virus (seov) viruses as well as to identify the natural host of khabarovsk virus (khav).201222967339
identification of a novel b-cell epitope of hantaan virus glycoprotein recognized by neutralizing 3d8 monoclonal antibody.hantaan virus (htnv), a member of the family bunyaviridae, is a major agent causing haemorrhagic fever with renal syndrome, a high-mortality-rate disease threatening approximately 150 000 people around the world yearly. the 3d8 mab displays a neutralizing activity to htnv infection. in this study, the b-cell epitopes of htnv glycoproteins (gps) were finely mapped by peptide scanning. a new b-cell epitope (882)gflcpefpgsfrkkc(896) of htnv, which locates on gc, has been screened out from a set of ...201222933664
dynamics of hantavirus infections in humans and animals in wuhan city, hubei, china.hemorrhagic fever with renal syndrome (hfrs) has been a significant public problem since the first cases were reported in 1961 in wuhan city (capital of hubei province of china). epidemiological surveys were carried out to better understand the dynamics of hantavirus infection in humans and animals in wuhan. during 1961-2011, a total of 21,820 hfrs cases were registered in wuhan. the two large epidemics had occurred during 1970-1991. they reached peaks in 1973 and 1983, respectively. there have ...201222910184
hantaan virus rna load in patients having hemorrhagic fever with renal syndrome: correlation with disease severity.to investigate the role of viral load in the pathogenesis of hemorrhagic fever with renal syndrome, the hantaan virus rna load in plasma from 101 patients was quantified, and the relationships between viral load and disease course, severity, and level of specific humoral immunity were analyzed. the viral load, detectable in 79 patients, ranged from 3.43 to 7.33 log10 copies/ml of plasma. in the early stage of disease, patients in severe/critical group were found to have higher viral loads than th ...201322869912
hantavirus infection among wild small mammals in vellore, south india.wild indigenous small mammals including 83 rodents (bandicoot and black rats, and house mice) and a shrew captured from multiple sites in vellore, south india, were tested for serological and molecular evidence of hantavirus infection. indirect immunofluorescence assay (ifa) using hantaan virus (htnv) antigen indicated hantavirus-reactive antibodies in 16 (19.3%) of 83 rodents (bandicoot and black rats). western blot (wb) using thailand virus (thaiv) antigen confirmed hantavirus-reactive antibod ...201322856552
cross-species transmission in the speciation of the currently known murinae-associated hantaviruses.to gain more insight into the phylogeny of dabieshan virus (dbsv), carried by niviventer confucianus and other murinae-associated hantaviruses, genome sequences of novel variants of dbsv were recovered from niviventer rats trapped in the mountainous areas of wenzhou, china. genetic analyses show that all known genetic variants of dbsv, including the ones identified in this study, are distinct from other murinae-associated hantaviruses. dbsv variants show geographic clustering and high intraspeci ...201222855492
hantaviruses in rodents and humans, xi'an, pr china.xi'an, the capital of shaanxi province, located in north-west china, is one of the major endemic areas for haemorrhagic fever with renal syndrome (hfrs). in this study, the epidemiological data of hfrs in xi'an from 1959 to 2010, especially in the past ten years (2001-2010), were surveyed. the features of hantavirus (hv) host carriers, the molecular characteristics of the hv s gene from hosts and patients, and the genome of the viral isolate were also investigated. data showed that there might b ...201222837422
isolation of hokkaido virus, genus hantavirus, using a newly established cell line derived from the kidney of the grey red-backed vole (myodes rufocanus bedfordiae).hantaviruses belong to the family bunyaviridae and are maintained in wild rodents. although vero e6 cells, which originate from african green monkey kidney, are used widely in hantavirus research, isolation of hantaviruses from this cell line is difficult. to develop an efficient method of propagation and isolation of hantaviruses we established a novel cell line, mrk101, derived from the kidney of the grey red-backed vole (myodes rufocanus bedfordiae), the natural host of hokkaido virus (hokv). ...201222791608
hantaan virus triggers tlr4-dependent innate immune responses.the innate immune response induced by hantavirus is responsible for endothelial cell dysfunction and viral pathogenicity. recent studies demonstrate that tlr4 expression is upregulated and mediates the secretion of several cytokines in hantaan virus (htnv)-infected endothelial cells. to examine viral interactions with host endothelial cells and characterize the innate antiviral responses associated with toll-like receptors, we selected tlr4 as the target molecule to investigate anti-hantavirus i ...201222775464
genetic characterization of a new subtype of hantaan virus isolated from a hemorrhagic fever with renal syndrome (hfrs) epidemic area in hubei province, china.to characterize hantaviruses currently circulating in the hemorrhagic fever with renal syndrome (hfrs) epidemic area of hubei province, rodents were captured and serum samples were collected from several hfrs patients. the partial s segment of the hantaviruses amplified from two serum samples had a high degree of sequence identity to the corresponding hantavirus strain isolated from apodemus agrarius (designated as hv004). the complete s, m, and l segment sequences of hv004 were determined. the ...201222718221
studies on hantavirus infection in small mammals captured in southern and central highland area of vietnam.to investigate the distribution of hantaviruses among animals in southern and central highland area of vietnam, a total of 1311 serum samples were obtained from rats and asian house shrews (suncus murinus) captured at 11 locations between 2006 and 2009. a total of 1066 serum samples from rats were examined for igg antibodies against hantaan virus, and there were 30 antibody-positive serum samples from rats that had been captured mainly in a port area and urban area in ho chi minh city (hcmc) (2. ...201222673720
hantaan virus surveillance in small mammals at firing points 10 and 60, yeoncheon, gyeonggi province, republic of korea.we used epidemiological data and indirect fluorescent antibody tests to determine the hantaan virus (htnv) antibody-positive (ab+) prevalence in small mammals captured at firing point 10 (fp-10) and firing point 60 (fp-60), gyeonggi province, near the demilitarized zone, republic of korea (rok), from 2001 to 2005. we used these data, combined with the partial m segment amplified from htnv recovered from lung tissues of apodemus agrarius, to clarify the genetic diversity and phylogenetic relation ...201222607077
seroprevalence of hantaviruses in small wild mammals trapped in south korea from 2005 to 2010.the seroprevalence of hantaan virus (htnv) in wild rodents in south korea was analyzed. wild rodents were trapped in 18 cities in eight provinces during 2005-2007 and on three islands and four mountains during 2008-2010. sera were collected from 629 out of 933 trapped wild animals and examined for immunoglobulin g antibodies to htnv using indirect immunofluorescence assays. apodemus agrarius (80.1%) was the most frequently captured species at almost all trapping sites. the overall prevalence of ...201222548542
dysregulation of the β3 integrin-vegfr2 complex in hantaan virus-directed hyperpermeability upon treatment with vegf.hantaviruses infect human endothelial cells (ecs) and are known to cause vascular-permeability-based diseases, including hemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). the αvβ3 integrins, which are highly expressed on the surface of ecs, serve as hantavirus receptors. specifically, the β3 integrin and vascular endothelial growth factor (vegf) receptor 2 (vegfr2) form a functional complex and interact with each other. signaling through this complex causes cy ...201222407444
isolation and characterization of hantaviruses in far east russia and etiology of hemorrhagic fever with renal syndrome in the region.hemorrhagic fever with renal syndrome (hfrs) is a serious public health issue in far east russia. two different hantaviruses were isolated from rodents captured in the khabarovsk region: amur virus (amrv; khekhtsir/ap209/2005 strain from apodemus peninsulae) and hantaan virus (htnv; galkino/aa57/2002 strain from a. agrarius). genetic analysis of the new isolates revealed that the m and l segments were apparently different between amrv and htnv, but s segments of the two viruses were closer. the ...201222403334
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
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