BACKGROUND Hemorrhagic fever with renal syndrome is caused by hantaviruses presenting with high fever,hemorrhage,and acute kidney injury.Microvascular injury and hemorrhage in mucus were often observed in patients wit...BACKGROUND Hemorrhagic fever with renal syndrome is caused by hantaviruses presenting with high fever,hemorrhage,and acute kidney injury.Microvascular injury and hemorrhage in mucus were often observed in patients with hantavirus infection.Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically.Here,we report a previously unreported case of hemorrhagic fever with concurrent aortic dissection.CASE SUMMARY A 56-year-old man complained of high fever and generalized body ache,with decreased platelet counts of 10×10^9/L and acute kidney injury.The enzymelinked immunosorbent assays test for immunoglobulin M and immunoglobulin G hantavirus-specific antibodies were both positive.During the convalescent period,he complained sudden onset acute chest pain radiating to the back,and the computed tomography angiography revealed an aortic dissection of the descending aorta extending to iliac artery.He was diagnosed with hemorrhagic fever with renal syndrome and Stanford B aortic dissection.The patient recovered completely after surgery with other support treatments.CONCLUSION Hemorrhagic fever with renal syndrome complicated with aortic dissection is rare and a difficult clinical condition.Hantavirus infection not only causes microvascular damage presenting with hemorrhage but may be risk factor for acute macrovascular detriment.A causal relationship has yet to be confirmed.展开更多
Objective To observe the application of continuous renal replacement therapy(CRRT) and heparin anticoagulation in patients with HFRS, and to explore a more suitable anticoagulant strategy. Methods Eighty-five severe-t...Objective To observe the application of continuous renal replacement therapy(CRRT) and heparin anticoagulation in patients with HFRS, and to explore a more suitable anticoagulant strategy. Methods Eighty-five severe-type patients(severe group) and 71 critical-type patients(critical group) were enrolled in this study. The frequency of CRRT was compared between the two groups; the frequency of CRRT treated with and without heparin anticoagulation and the frequency of hemorrhage and channel blood clotting induced by the two anticoagulant strategies were observed. Results The frequency of CRRT in the critical group was higher than that in the severe group(P < 0.001). The frequency of CRRT initiated during the overlapping phases in the critical group was significantly higher than that of the severe group(P = 0.032). The total times of CRRT was 103, and 70 of them were treated with heparin anticoagulation. The frequencies of hemorrhage induced by heparin anticoagulation and no heparinization were 16 and 0, respectively, and the frequencies of channel blood clotting were 2 and 4, respectively. Conclusions CRRT has been used extensively in the critical-type patients with HFRS. The heparin anticoagulation and no anticoagulant strategies should be used more rationally in patients treated with CRRT, according to the clinical characteristics of the disease.展开更多
Objective:To explore and analyze the effect of high-quality nursing on patients with epidemic hemorrhagic fever with renal syndrome.Methods:Ninety patients with epidemic hemorrhagic fever with renal syndrome treated i...Objective:To explore and analyze the effect of high-quality nursing on patients with epidemic hemorrhagic fever with renal syndrome.Methods:Ninety patients with epidemic hemorrhagic fever with renal syndrome treated in Huyi District People’s Hospital from October 2021 to January 2022 were randomly divided into an experimental group and a control group,with 45 cases in each group.The control group received routine nursing and the experimental group received high-quality nursing.The effect of routine nursing and high-quality nursing were compared and analyzed based on the Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),the degree of satisfaction with nursing care,and the patients’quality of life.Results:Before nursing,there was no significant difference in the patients’psychological state between the two groups(P>0.05);after nursing,there was significant difference in the patients’psychological state between the two groups(P<0.05);the degree of satisfaction with nursing care of the experimental group was significantly higher than that of the control group(P<0.05);comparing the quality of life of the two groups,the quality-of-life score of the control group was significantly lower than that of the experimental group(P<0.05).Conclusion:For patients with epidemic hemorrhagic fever with renal syndrome,high-quality nursing can significantly and effectively improve their psychological state,level of satisfaction with nursing care,and quality of life.展开更多
Infection with the Hantaan virus(HTNV)may result in severe hemorrhagic fever with renal syndrome(HFRS).The functions of HLA-E-restricted CD8^(+)T lymphocytes in virus control and vaccine development have recently rece...Infection with the Hantaan virus(HTNV)may result in severe hemorrhagic fever with renal syndrome(HFRS).The functions of HLA-E-restricted CD8^(+)T lymphocytes in virus control and vaccine development have recently received increased attention.The purpose of this research is to discover HLA-E-restricted CD8^(+)T cell epitopes on HTNV as well as the features of these epitope-specific CD8^(+)T cells in HFRS patients.To anticipate HLA-Erestricted HTNV epitopes,the NetMHCpan servers were utilized.The K562/HLA-E cell binding test and the enzyme-linked immunospot assay were used to confirm epitope binding to HLA-E.The number and features of HLA-E-restricted epitope-specific CD8^(+)T lymphocytes in HFRS patients were investigated using tetramer staining,intracellular cytokine labeling,proliferation,and cytotoxicity assays.Six HTNV-derived HLA-Erestricted CD8^(+)T cell epitopes were found in this study.In mild/moderate HFRS patients,the frequency of HLA-E-restricted epitope-specific CD8^(+)T cells was greater than in severe/critical patients.CD38+HLA-DR+HLA-E-restricted CD8^(+)T cells were identified.Meanwhile,CD45RA^(+)CCR7^(-)effector memory-re-expressing CD45RA T cells with early and intermediate maturation and differentiation characteristics predominated.Notably,CD8^(+)T cells from milder HFRS patients produced more interferon-γ,interleukin-2,and granzyme B,had a stronger proliferative potential,and were inversely linked with the amount of plasma HTNV virus load.Furthermore,HLA-E-restricted epitope-specific CD8^(+)T cells demonstrated improved cytotoxic activity in vitro during the acute stage of HFRS.Taken together,the findings demonstrate the protective effects of HLA-E-restricted CD8^(+)T cells during HTNV infection,suggesting that HLA-E-targeted vaccines against HTNV might be developed for HLA-diverse populations.展开更多
Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor ne...Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β2-microglobulin (β2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.展开更多
Hemorrhagic fever with renal syndrome(HFRS)is an acute natural focus epidemic disease characterized by fever,shock,hemorrhage and kidney injury caused by hantavirus infection.Hantavirus mainly infects human vascular e...Hemorrhagic fever with renal syndrome(HFRS)is an acute natural focus epidemic disease characterized by fever,shock,hemorrhage and kidney injury caused by hantavirus infection.Hantavirus mainly infects human vascular endothelial cells,and induces extensive damage to small blood vessels and capillaries.Increased vascular permeability is the pathological basis for clinical manifestations of HFRS.Although domestic and foreign scholars have carried out many studies on the hantavirus pathogenesis,such as the immune pathological response induced by hantavirus,host genetics and apoptosis,thrombocytopenia,coagulation and fibrinolysis dysfunction,and the vascular endothelial damage,the pathogenesis of HFRS has not been fully elucidated and there is no effective drug yet.In-depth discussion of the molecular mechanism of HFRS and finding effective therapeutic drugs are still the research hotspots on the field of hantavirus/HFRS.This review will elaborate the research progress on the pathogenesis of HFRS in recent years.展开更多
Hemorrhagic fever with renal syndrome(HFRS)is an acute zoonosis with a global distribution.China is one of the countries with a high incidence of HFRS,which has long endangered the lives and health of the Chinese peop...Hemorrhagic fever with renal syndrome(HFRS)is an acute zoonosis with a global distribution.China is one of the countries with a high incidence of HFRS,which has long endangered the lives and health of the Chinese people.The Infectious Disease Branch of the Chinese Preventive Medicine Association and the Infectious Diseases Branch of the Chinese Medical Association organized national multidisciplinary experts,based on domestic and international research results combined with experts’practical experiences,to reach this consensus after thorough discussion.This consensus contains 17 recommendations aimed at prevention and identification of important clinical issues to further standardize the prevention,diagnosis,and treatment of HFRS.展开更多
Objective The Guanzhong Plain of Shaanxi Province is a severely afflicted hemorrhagic fever with renal syndrome(HFRS)epidemic area,while HFRS prevalence has decreased in most epidemic areas in China.Little information...Objective The Guanzhong Plain of Shaanxi Province is a severely afflicted hemorrhagic fever with renal syndrome(HFRS)epidemic area,while HFRS prevalence has decreased in most epidemic areas in China.Little information is available regarding the leading fine-scale influencing factors in this highly HFRSconcentrated area and the roles of natural environmental and socioeconomic factors.To investigate this,two regions in the Guanzhong Plain,that is,the Chang’an District and Hu County,with similar geographical environments,different levels of economic development,and high epidemic prevalence,were chosen as representative areas of the HFRS epidemic.Methods Maximum entropy models were constructed based on HFRS cases and fine-scale influencing factors,including meteorological,natural environmental,and socioeconomic factors,from 2014 to 2016.Results More than 95% of the HFRS cases in the study area were located in the northern plains,which has an altitude of less than 800 m,with topography contributed 84.1% of the impact on the spatial differentiation of the HFRS epidemic.In the northern plains,precipitation and population density jointly affected the spatial differentiation of the HFRS epidemic,with contribution rates of 60.7% and 28.0%,respectively.By comparing the influencing factors of the northern plains of Chang’an District and Hu County,we found that precipitation and the normalized difference vegetation index(NDVI)dominated the HFRS epidemic in the relatively developed Chang’an District,while land-use type,temperature,precipitation and population density dominated the HFRS epidemic in the relatively undeveloped Hu County.Conclusion Topography was the primary key factor for HFRS prevalence in the Chang’an District and Hu County,and the spatial differentiation of HFRS was dominated by precipitation and population density in the northern plains.Compared with the influencing factors of the relatively developed Chang’an District,the developing Hu County was more affected by socioeconomic factors.When formulating targeted HFRS epidemic prevention and control strategies in the targeted areas,it is crucial to consider the local economic development state and combine natural environmental factors,including the meteorological environment and vegetation coverage.展开更多
The Hantaan virus(HTNV)and Seoul virus(SEOV)mutants have accumulated over time.It is important to determine whether their neutralizing epitopes have evolved,thereby making the current vaccine powerless.However,it is i...The Hantaan virus(HTNV)and Seoul virus(SEOV)mutants have accumulated over time.It is important to determine whether their neutralizing epitopes have evolved,thereby making the current vaccine powerless.However,it is impossible to determine by using traditional plaque reduction neutralization test(PRNT),because it requires large numbers of live mutant strains.Pseudovirus-based neutralization assays(PBNA)were developed by employing vesicular stomatitis virus(VSV)backbone incorporated with HTNV or SEOV glycoproteins(VSVDG*-HTNVG or VSVDG*-SEOVG).56 and 51 single amino acid substitutions of glycoprotein(GP)in HTNV and SEOV were selected and introduced into the reference plasmid.Then the mutant pseudoviruses were generated and tested by PBNA.The PBNA results were highly correlated with PRNT ones with R2 being 0.91 for VSVDG*-HTNVG and 0.82 for VSVDG*-SEOVG.53 HTNV mutant pseudoviruses and 46 SEOV mutants were successfully generated.Importantly,by using PBNA,we found that HTNV or SEOV immunized antisera could neutralize all the corresponding 53 HTNV mutants or the 46 SEOV mutants respectively.The novel PBNA enables us to closely monitor the effectiveness of vaccines against large numbers of evolving HTNV and SEOV.And the current vaccine remains to be effective for the naturally occurring mutants.展开更多
文摘BACKGROUND Hemorrhagic fever with renal syndrome is caused by hantaviruses presenting with high fever,hemorrhage,and acute kidney injury.Microvascular injury and hemorrhage in mucus were often observed in patients with hantavirus infection.Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically.Here,we report a previously unreported case of hemorrhagic fever with concurrent aortic dissection.CASE SUMMARY A 56-year-old man complained of high fever and generalized body ache,with decreased platelet counts of 10×10^9/L and acute kidney injury.The enzymelinked immunosorbent assays test for immunoglobulin M and immunoglobulin G hantavirus-specific antibodies were both positive.During the convalescent period,he complained sudden onset acute chest pain radiating to the back,and the computed tomography angiography revealed an aortic dissection of the descending aorta extending to iliac artery.He was diagnosed with hemorrhagic fever with renal syndrome and Stanford B aortic dissection.The patient recovered completely after surgery with other support treatments.CONCLUSION Hemorrhagic fever with renal syndrome complicated with aortic dissection is rare and a difficult clinical condition.Hantavirus infection not only causes microvascular damage presenting with hemorrhage but may be risk factor for acute macrovascular detriment.A causal relationship has yet to be confirmed.
基金supported by the National Basic Research Program of China (973 Program) (No. 2012CB518905)National Natural Science Foundation of China (No. 81071370)
文摘Objective To observe the application of continuous renal replacement therapy(CRRT) and heparin anticoagulation in patients with HFRS, and to explore a more suitable anticoagulant strategy. Methods Eighty-five severe-type patients(severe group) and 71 critical-type patients(critical group) were enrolled in this study. The frequency of CRRT was compared between the two groups; the frequency of CRRT treated with and without heparin anticoagulation and the frequency of hemorrhage and channel blood clotting induced by the two anticoagulant strategies were observed. Results The frequency of CRRT in the critical group was higher than that in the severe group(P < 0.001). The frequency of CRRT initiated during the overlapping phases in the critical group was significantly higher than that of the severe group(P = 0.032). The total times of CRRT was 103, and 70 of them were treated with heparin anticoagulation. The frequencies of hemorrhage induced by heparin anticoagulation and no heparinization were 16 and 0, respectively, and the frequencies of channel blood clotting were 2 and 4, respectively. Conclusions CRRT has been used extensively in the critical-type patients with HFRS. The heparin anticoagulation and no anticoagulant strategies should be used more rationally in patients treated with CRRT, according to the clinical characteristics of the disease.
文摘Objective:To explore and analyze the effect of high-quality nursing on patients with epidemic hemorrhagic fever with renal syndrome.Methods:Ninety patients with epidemic hemorrhagic fever with renal syndrome treated in Huyi District People’s Hospital from October 2021 to January 2022 were randomly divided into an experimental group and a control group,with 45 cases in each group.The control group received routine nursing and the experimental group received high-quality nursing.The effect of routine nursing and high-quality nursing were compared and analyzed based on the Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),the degree of satisfaction with nursing care,and the patients’quality of life.Results:Before nursing,there was no significant difference in the patients’psychological state between the two groups(P>0.05);after nursing,there was significant difference in the patients’psychological state between the two groups(P<0.05);the degree of satisfaction with nursing care of the experimental group was significantly higher than that of the control group(P<0.05);comparing the quality of life of the two groups,the quality-of-life score of the control group was significantly lower than that of the experimental group(P<0.05).Conclusion:For patients with epidemic hemorrhagic fever with renal syndrome,high-quality nursing can significantly and effectively improve their psychological state,level of satisfaction with nursing care,and quality of life.
基金the National Natural Science Foundation of China,grant number 81871239Technical Field of Foundation Strengthening Plan Projects,grant number 2019‐JCJQ‐JJ‐094National Natural Science Foundation of China,grant number 81771705 and 81901600.
文摘Infection with the Hantaan virus(HTNV)may result in severe hemorrhagic fever with renal syndrome(HFRS).The functions of HLA-E-restricted CD8^(+)T lymphocytes in virus control and vaccine development have recently received increased attention.The purpose of this research is to discover HLA-E-restricted CD8^(+)T cell epitopes on HTNV as well as the features of these epitope-specific CD8^(+)T cells in HFRS patients.To anticipate HLA-Erestricted HTNV epitopes,the NetMHCpan servers were utilized.The K562/HLA-E cell binding test and the enzyme-linked immunospot assay were used to confirm epitope binding to HLA-E.The number and features of HLA-E-restricted epitope-specific CD8^(+)T lymphocytes in HFRS patients were investigated using tetramer staining,intracellular cytokine labeling,proliferation,and cytotoxicity assays.Six HTNV-derived HLA-Erestricted CD8^(+)T cell epitopes were found in this study.In mild/moderate HFRS patients,the frequency of HLA-E-restricted epitope-specific CD8^(+)T cells was greater than in severe/critical patients.CD38+HLA-DR+HLA-E-restricted CD8^(+)T cells were identified.Meanwhile,CD45RA^(+)CCR7^(-)effector memory-re-expressing CD45RA T cells with early and intermediate maturation and differentiation characteristics predominated.Notably,CD8^(+)T cells from milder HFRS patients produced more interferon-γ,interleukin-2,and granzyme B,had a stronger proliferative potential,and were inversely linked with the amount of plasma HTNV virus load.Furthermore,HLA-E-restricted epitope-specific CD8^(+)T cells demonstrated improved cytotoxic activity in vitro during the acute stage of HFRS.Taken together,the findings demonstrate the protective effects of HLA-E-restricted CD8^(+)T cells during HTNV infection,suggesting that HLA-E-targeted vaccines against HTNV might be developed for HLA-diverse populations.
文摘Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β2-microglobulin (β2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.
基金supported by the General Clinical Research Project of Technology Innovation and Development Foundation in the Second Affiliated Hospital of Air Force Medical University(No.2019LCYJ011)the National Science and Technology Major Project(No.2017ZX10204401-002-005)+1 种基金the Key Clinical Research Project of Technology Innovation and Development Foundation in the Second Affiliated Hospital of Air Force Medical University(No.2019LCYJ002)the National Natural Science Foundation of China(No.81373118).
文摘Hemorrhagic fever with renal syndrome(HFRS)is an acute natural focus epidemic disease characterized by fever,shock,hemorrhage and kidney injury caused by hantavirus infection.Hantavirus mainly infects human vascular endothelial cells,and induces extensive damage to small blood vessels and capillaries.Increased vascular permeability is the pathological basis for clinical manifestations of HFRS.Although domestic and foreign scholars have carried out many studies on the hantavirus pathogenesis,such as the immune pathological response induced by hantavirus,host genetics and apoptosis,thrombocytopenia,coagulation and fibrinolysis dysfunction,and the vascular endothelial damage,the pathogenesis of HFRS has not been fully elucidated and there is no effective drug yet.In-depth discussion of the molecular mechanism of HFRS and finding effective therapeutic drugs are still the research hotspots on the field of hantavirus/HFRS.This review will elaborate the research progress on the pathogenesis of HFRS in recent years.
文摘Hemorrhagic fever with renal syndrome(HFRS)is an acute zoonosis with a global distribution.China is one of the countries with a high incidence of HFRS,which has long endangered the lives and health of the Chinese people.The Infectious Disease Branch of the Chinese Preventive Medicine Association and the Infectious Diseases Branch of the Chinese Medical Association organized national multidisciplinary experts,based on domestic and international research results combined with experts’practical experiences,to reach this consensus after thorough discussion.This consensus contains 17 recommendations aimed at prevention and identification of important clinical issues to further standardize the prevention,diagnosis,and treatment of HFRS.
基金funded by the National Natural Science Foundation of China[grant number 41901337 and 42071136]。
文摘Objective The Guanzhong Plain of Shaanxi Province is a severely afflicted hemorrhagic fever with renal syndrome(HFRS)epidemic area,while HFRS prevalence has decreased in most epidemic areas in China.Little information is available regarding the leading fine-scale influencing factors in this highly HFRSconcentrated area and the roles of natural environmental and socioeconomic factors.To investigate this,two regions in the Guanzhong Plain,that is,the Chang’an District and Hu County,with similar geographical environments,different levels of economic development,and high epidemic prevalence,were chosen as representative areas of the HFRS epidemic.Methods Maximum entropy models were constructed based on HFRS cases and fine-scale influencing factors,including meteorological,natural environmental,and socioeconomic factors,from 2014 to 2016.Results More than 95% of the HFRS cases in the study area were located in the northern plains,which has an altitude of less than 800 m,with topography contributed 84.1% of the impact on the spatial differentiation of the HFRS epidemic.In the northern plains,precipitation and population density jointly affected the spatial differentiation of the HFRS epidemic,with contribution rates of 60.7% and 28.0%,respectively.By comparing the influencing factors of the northern plains of Chang’an District and Hu County,we found that precipitation and the normalized difference vegetation index(NDVI)dominated the HFRS epidemic in the relatively developed Chang’an District,while land-use type,temperature,precipitation and population density dominated the HFRS epidemic in the relatively undeveloped Hu County.Conclusion Topography was the primary key factor for HFRS prevalence in the Chang’an District and Hu County,and the spatial differentiation of HFRS was dominated by precipitation and population density in the northern plains.Compared with the influencing factors of the relatively developed Chang’an District,the developing Hu County was more affected by socioeconomic factors.When formulating targeted HFRS epidemic prevention and control strategies in the targeted areas,it is crucial to consider the local economic development state and combine natural environmental factors,including the meteorological environment and vegetation coverage.
基金supported by the National Science and Technology Major Projects of Drug Discovery[Grant Number 2018ZX09101-001]
文摘The Hantaan virus(HTNV)and Seoul virus(SEOV)mutants have accumulated over time.It is important to determine whether their neutralizing epitopes have evolved,thereby making the current vaccine powerless.However,it is impossible to determine by using traditional plaque reduction neutralization test(PRNT),because it requires large numbers of live mutant strains.Pseudovirus-based neutralization assays(PBNA)were developed by employing vesicular stomatitis virus(VSV)backbone incorporated with HTNV or SEOV glycoproteins(VSVDG*-HTNVG or VSVDG*-SEOVG).56 and 51 single amino acid substitutions of glycoprotein(GP)in HTNV and SEOV were selected and introduced into the reference plasmid.Then the mutant pseudoviruses were generated and tested by PBNA.The PBNA results were highly correlated with PRNT ones with R2 being 0.91 for VSVDG*-HTNVG and 0.82 for VSVDG*-SEOVG.53 HTNV mutant pseudoviruses and 46 SEOV mutants were successfully generated.Importantly,by using PBNA,we found that HTNV or SEOV immunized antisera could neutralize all the corresponding 53 HTNV mutants or the 46 SEOV mutants respectively.The novel PBNA enables us to closely monitor the effectiveness of vaccines against large numbers of evolving HTNV and SEOV.And the current vaccine remains to be effective for the naturally occurring mutants.