Chikungunya fever is a vector-borne viral disease transmitted to humans by chikungunya virus(CHIKV)-infected mosquitoes.There have been many outbreaks of CHIKV infection worldwide,and the virus poses ongoing risks to ...Chikungunya fever is a vector-borne viral disease transmitted to humans by chikungunya virus(CHIKV)-infected mosquitoes.There have been many outbreaks of CHIKV infection worldwide,and the virus poses ongoing risks to global health.To prevent and control CHIKV infection,it is important to improve the current CHIKV diagnostic approaches to allow for the detection of low CHIKV concentrations and to correctly distinguish CHIKV infections from those due to other mosquito-transmitted viruses,including dengue virus(DENV),Japanese encephalitis virus(JEV),and Zika virus(ZIKV).Here,we produced monoclonal antibodies(mAbs)against the CHIKV envelope 2 protein(CHIKV-E2)and compared their sensitivity and specificity with commercially available mAbs using enzyme-linked immunosorbent assays(ELISA).Two anti-CHIKV-E2 mAbs,19-1 and 21-1,showed higher binding affinities to CHIKV-E2 protein than the commercial mAbs did.In particular,the 19-1 mAb had the strongest binding affinity to inactivated CHIKV.Moreover,the 19-1 mAb had very little cross-reactivity with other mosquito-borne viruses,such as ZIKV,JEV,and DENV.These results suggest that the newly produced anti-CHIKV-E2 mAb,19-1,could he used for CHIKV diagnostic approaches.展开更多
Chikungunya virus(CHIKV) is a mosquito-borne virus that causes epidemics widely in the world especially in the tropical and subtropical regions. Phylogenetic analysis has found that the CHIKV lineages were associated ...Chikungunya virus(CHIKV) is a mosquito-borne virus that causes epidemics widely in the world especially in the tropical and subtropical regions. Phylogenetic analysis has found that the CHIKV lineages were associated with the spatial and temporal distributions, which were related to the virus adaption to the major mosquito species and their distributions. In this study, we reported the complete genome sequences of eight CHIKV isolates from the outbreak in Pakistan last year. Then we reviewed the evolutionary history using extensive phylogenetic analysis, analyzed lineagespecific substitutions in viral proteins, and characterized the spreading pathway of CHIKV strains including the Pakistani strains. The results showed that the Pakistani stains belonged to the ECSA.IOL sub-lineage and derived from India. The genetic properties of the Pakistani strains including the adaptive substitution to vectors were further characterized, and the potential risks from the occurrence of CHIKV infection in Pakistan were discussed. These results provided better understanding of CHIKV evolution and transmission in the world and revealed the possible origination of the CHIKV outbreak and epidemic in Pakistan, which would promote the disease prevention and control in the identified countries and territories with the history of CHIKV infections as well as new regions with potential risk of CHIKV outbreaks.展开更多
With the broad spread of the chikungunya virus(CHIkV),there is an increasing demand for more effective and broadly protective vaccines.Here,we designed CHIkV mRNA vaccines containing full-length structural proteins or...With the broad spread of the chikungunya virus(CHIkV),there is an increasing demand for more effective and broadly protective vaccines.Here,we designed CHIkV mRNA vaccines containing full-length structural proteins or part of structural proteins(envelope proteins)based on conserved sequences from 769 viral strains encompassing four lineages.The vaccine induced strong cellular and humoral immune responses in BALB/c mice and provided robust protection.Immunization of BALB/c mice with either of the two vaccines induced high levels of neutralizing antibodies against pseudoviruses from four distinct lineages,highlighting their potential for broad cross-lineage protective efficacy.Immunoglobulin repertoire analysis revealed two important BCR V-J gene combinations,IgHV1-4-lgHJ3 and IgHV1-4-lgHJ2,and lineage-specific immunity analysis revealed significant upregulation of TCRs containing V19 and V20.BCR and TCR immunodiversity may be a potential reason for the broad-spectrum protection against CHIkV afforded by the vaccine.In A129 mice,it elicited lower levels of neutralizing antibodies but prevented mouse mortality and cleared chronic infection.In the rhesus macaque model,both vaccines elicited a certain level of humoral and cellular immune responses and protected the rhesus macaques from the CHikV challenge.In conclusion,the results from both mouse and rhesus macaque models indicate that the vaccine could be a candidate for clinical useagainst CHIKV.展开更多
Background:Chikungunya virus(CHIKV)is an infectious agent that caused several outbreaks among different countries and affected approximately 1.3 million Indian populations.It is transmitted by Aedes mosquito–either A...Background:Chikungunya virus(CHIKV)is an infectious agent that caused several outbreaks among different countries and affected approximately 1.3 million Indian populations.It is transmitted by Aedes mosquito–either A.albopictus or A.aegypti.Generally,the clinical manifestations of CHIKV infection involve high-grade fever,joint pain,skin rashes,headache,and myalgia.The present study aims to investigate the relationship between the CHIKV virus load and clinical symptoms of the CHIKV infection so that better patient management can be done in the background of the CHIKV outbreak as there is no licensed anti-viral drug and approved vaccines available against CHIKV.Methods:CHIKV RTPCR positive samples(n=18)(Acute febrile patients having D.O.F≤7 days)were taken for the quantification of CHIKV viremia by Real-Time PCR.Clinical features of the febrile patients were recorded during the collection of blood samples.Results:The log mean virus load of 18 RT-PCR-positive samples was 1.3×10^(6) copies/mL(1.21×10^(3)–2.33×10^(8) copies/mL).Among the observed clinical features,the log mean virus load(CHIKV)of the patients without skin rash is higher than in the patients with skin rash(6.61 vs.5.5,P=0.0435).Conclusion:The conclusion of the study was that the patients with skin rashes had lower viral load and those without skin rashes had higher viral load.展开更多
Rationale:Transmitted to humans via the Aedes mosquito,Chikungunya virus(CHIKV)is associated with multi-system complications,sometimes collectively referred to as“atypical features.”However,a disorder of the nervous...Rationale:Transmitted to humans via the Aedes mosquito,Chikungunya virus(CHIKV)is associated with multi-system complications,sometimes collectively referred to as“atypical features.”However,a disorder of the nervous system appears to be the most common severe complication of CHIKV infection.Patient’s Concern:A seventy-five-year-old patient from India presented to the hospital with fever,chills,rigors,and multiple joint pains for which he was worked up.Diagnosis:CHIKV encephalitis.Interventions:The patient was treated initially on supportive therapy with antipyretics,intravenous fluids;however,during his hospital stay,the patient had altered sensorium during which he was managed in the intensive care unit;required mechanical ventilation.Outcomes:The patient sccumbed to his illness.Lessons:Treating clinicians should keep CHIKV disease in the differential diagnosis in cases of febrile exanthems associated with disabling arthritis,especially in a CHIKV-endemic country like India.展开更多
As a matter of fact, infectious diseases hamper everyone’s life and produce a lifelong threat to everyone neutral of age, sex, lifestyle and socio-economic status. Nowadays, come into the sight of Chikungunya viral (...As a matter of fact, infectious diseases hamper everyone’s life and produce a lifelong threat to everyone neutral of age, sex, lifestyle and socio-economic status. Nowadays, come into the sight of Chikungunya viral (CHIKV) infection injured many Asian and African countries, also deliberated threat in rising countries and also low socio-economic countries. CHIKV is a positive-sense, enveloped single-stranded, RNA virus belonging to the genus Alphavirus, family Togaviridae. As the Dengue & Chikungunya viruses are spread simultaneously at the same time, so it is tough to identify them. In our resource-limited countries, swift detection of CHIKV by RT-LAMP is the simplest molecular technique in low-equipment settings without the use of any expensive decoration. Heat-treated centrifuged and uncentrifuged samples were used in this study and they showed the same result (100%). Different instruments like heat block, water bath, conventional thermal cycler & real-time thermal cycler were used to amplify the CHIKV RNA and they indicated that 100% samples were identified by all four instruments. The amplified products were visualized by turbidity test, color change by HNB, step-ladder band pattern in agarose gel electrophoresis and amplification curve in real-time thermal cycler naked eye, here the results also showed 100% samples were determined by all visualized methods. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a recent technique for amplifying RNA under limited temperature, with high tangibility, quickness and competency. To identify the CHIKV RNA Reverse transcription loop-mediated isothermal amplification was fabricated and validated, and the results were also compared with reverse transcription polymerase chain reaction (RT-PCR). The sensitivity was 95.71% and specificity was 100%, these results indicate that RT-LAMP is a feasible method for quick detection of CHIKV RNA.展开更多
目的对1例缅甸输入基孔肯雅热病例血清标本进行病毒分离及全基因组测序,分析其基因特征。方法采用real-time RT-PCR方法对标本进行检测,分离培养后获得毒株,对病毒核酸扩增后的产物进行全基因组测序,使用DNAStar 7.1软件对测序结果进行...目的对1例缅甸输入基孔肯雅热病例血清标本进行病毒分离及全基因组测序,分析其基因特征。方法采用real-time RT-PCR方法对标本进行检测,分离培养后获得毒株,对病毒核酸扩增后的产物进行全基因组测序,使用DNAStar 7.1软件对测序结果进行拼接,Mega5.0软件对序列进行比对和系统发生树构建。结果病例血清标本核酸检测显示CHIKV阳性,经分离培养获得CHIKV毒株(YN0627株),全基因组测序得到其序列,YN0627全长为11586 nt,其基因结构符合CHIKV的基因特征。系统进化分析显示,YN0627与东中南非洲遗传谱系(East,Central and South African Lineage,ECSA)的其他流行株聚集在一起,属于ECSA谱系。YN0627的编码区与参考序列相比,核苷酸同源性为85.24%~99.96%,氨基酸同源性为95.34%~99.97%,结构蛋白编码区域有28个氨基酸变异位点。结论云南省输入性CHIKV-YN0627属于ECSA谱系,且观察到多个氨基酸位点突变,提示云南省应当加强对CHIKV的监测和研究。展开更多
Chikungunva virus is a mosquito-transmitted alphavirus that causes chikungunva fever,a febrile illness associated with severe arthralgia and rash.Chikungunva virus is transmitted by culicine mosquitoes:Chikungunya vir...Chikungunva virus is a mosquito-transmitted alphavirus that causes chikungunva fever,a febrile illness associated with severe arthralgia and rash.Chikungunva virus is transmitted by culicine mosquitoes:Chikungunya virus replicates in the skin,disseminates to liver,muscle,joints.lymphoid tissue and brain,presumably through the blood.Phylogenetic studies showed that the Indian Ocean and the Indian subcontinent epidemics were caused by two different introductions of distinct strains of East/Central/South African genotype of CHIKV.The paraphyletic grouping of African CHIK viruses supports the historical evidence that the virus was introduced into Asia from Africa.Phylogenetic analysis divided Chikungunva virus isolates into three distinct genotypes based on geographical origins:the first,the West Africa genotype,consisted of isolates from Senegal and Nigeria;the second contained strains from East/Central/South African genotype,while the third contained solely Asian.The most recent common ancestor for the recent epidemic,which ravaged Indian Ocean islands and Indian subcontinent in 2004- 2007.was found to date in 2002.Asian lineage dated about 1952 and exhibits similar spread patterns of the recent Indian Ocean outbreak lineage,with successive epidemics detected along an eastward path.Asian group splitted into two clades:an Indian lineage and a south east lineage.Outbreaks of Chikungunya virus fever in Asia have not been associated necessarily with outbreaks in Africa.Phylogenetic tools can reconstruct geographic spread of Chikungunva virus during the epidemics wave.The good management of patients with acute Chikungunva virus infection is essential for public health in susceptible areas with current Aedes spp activity.展开更多
Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America ...Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America suddenly, causing major regional epidemics recently and becoming a notable global health problem. Infection by CHIKV results in a spectrum of clinical diseases including an acute self-limiting febrile illness in most individuals, a chronic phase of recurrent join pain in a proportion of patients, and long-term arthralgia for months to years for the unfortunate few. No specific anti-viral drugs or licensed vaccines for CHIKV are available so far. A better understanding of virus-host interactions is essential for the development of therapeutics and vaccines. To this end, we reviewed the existing knowledge on CHIKV's epidemiology, clinical presentation, molecular virology, diagnostic approaches, host immune response, vaccine development, and available animal models. Such a comprehensive overview, we believe, will shed lights on the promises and challenges in CHIKV vaccine development.展开更多
基金supported by Grants from the R&D Convergence Program of National Research Council of Science & Technology (No. CAP-16-02-KIST)the National Research Foundation of Korea (No. NRF-2016M3A9B6918584)
文摘Chikungunya fever is a vector-borne viral disease transmitted to humans by chikungunya virus(CHIKV)-infected mosquitoes.There have been many outbreaks of CHIKV infection worldwide,and the virus poses ongoing risks to global health.To prevent and control CHIKV infection,it is important to improve the current CHIKV diagnostic approaches to allow for the detection of low CHIKV concentrations and to correctly distinguish CHIKV infections from those due to other mosquito-transmitted viruses,including dengue virus(DENV),Japanese encephalitis virus(JEV),and Zika virus(ZIKV).Here,we produced monoclonal antibodies(mAbs)against the CHIKV envelope 2 protein(CHIKV-E2)and compared their sensitivity and specificity with commercially available mAbs using enzyme-linked immunosorbent assays(ELISA).Two anti-CHIKV-E2 mAbs,19-1 and 21-1,showed higher binding affinities to CHIKV-E2 protein than the commercial mAbs did.In particular,the 19-1 mAb had the strongest binding affinity to inactivated CHIKV.Moreover,the 19-1 mAb had very little cross-reactivity with other mosquito-borne viruses,such as ZIKV,JEV,and DENV.These results suggest that the newly produced anti-CHIKV-E2 mAb,19-1,could he used for CHIKV diagnostic approaches.
基金supported by the Science and Technology Basic Work Program(2013FY113500)from the Ministry of Science and Technology of Chinathe International Cooperation on key Technologies of Biosafety along the China-Pakistan Economic Corridor(153B42KYSB2017 0004)+1 种基金the Strategic Bio-resource Service Network Plan and Building the Biogenetic Resource Preserving Capacity Program from the Chinese Academy of Sciences(ZSSB-002)funded by the National Basic Scientific Data Sharing-Service Platform(XXH12504-3-15)
文摘Chikungunya virus(CHIKV) is a mosquito-borne virus that causes epidemics widely in the world especially in the tropical and subtropical regions. Phylogenetic analysis has found that the CHIKV lineages were associated with the spatial and temporal distributions, which were related to the virus adaption to the major mosquito species and their distributions. In this study, we reported the complete genome sequences of eight CHIKV isolates from the outbreak in Pakistan last year. Then we reviewed the evolutionary history using extensive phylogenetic analysis, analyzed lineagespecific substitutions in viral proteins, and characterized the spreading pathway of CHIKV strains including the Pakistani strains. The results showed that the Pakistani stains belonged to the ECSA.IOL sub-lineage and derived from India. The genetic properties of the Pakistani strains including the adaptive substitution to vectors were further characterized, and the potential risks from the occurrence of CHIKV infection in Pakistan were discussed. These results provided better understanding of CHIKV evolution and transmission in the world and revealed the possible origination of the CHIKV outbreak and epidemic in Pakistan, which would promote the disease prevention and control in the identified countries and territories with the history of CHIKV infections as well as new regions with potential risk of CHIKV outbreaks.
基金supported by the CAMS Innovation Fund for Medical Sciences(2022-I2M-CoV19-002,2021-12M-1-038,2023-12M-2-001)Key project of basic research in Yunnan Province(202401As070049)Major project of basic research in Yunnan Province(202401BC070008)。
文摘With the broad spread of the chikungunya virus(CHIkV),there is an increasing demand for more effective and broadly protective vaccines.Here,we designed CHIkV mRNA vaccines containing full-length structural proteins or part of structural proteins(envelope proteins)based on conserved sequences from 769 viral strains encompassing four lineages.The vaccine induced strong cellular and humoral immune responses in BALB/c mice and provided robust protection.Immunization of BALB/c mice with either of the two vaccines induced high levels of neutralizing antibodies against pseudoviruses from four distinct lineages,highlighting their potential for broad cross-lineage protective efficacy.Immunoglobulin repertoire analysis revealed two important BCR V-J gene combinations,IgHV1-4-lgHJ3 and IgHV1-4-lgHJ2,and lineage-specific immunity analysis revealed significant upregulation of TCRs containing V19 and V20.BCR and TCR immunodiversity may be a potential reason for the broad-spectrum protection against CHIkV afforded by the vaccine.In A129 mice,it elicited lower levels of neutralizing antibodies but prevented mouse mortality and cleared chronic infection.In the rhesus macaque model,both vaccines elicited a certain level of humoral and cellular immune responses and protected the rhesus macaques from the CHikV challenge.In conclusion,the results from both mouse and rhesus macaque models indicate that the vaccine could be a candidate for clinical useagainst CHIKV.
文摘Background:Chikungunya virus(CHIKV)is an infectious agent that caused several outbreaks among different countries and affected approximately 1.3 million Indian populations.It is transmitted by Aedes mosquito–either A.albopictus or A.aegypti.Generally,the clinical manifestations of CHIKV infection involve high-grade fever,joint pain,skin rashes,headache,and myalgia.The present study aims to investigate the relationship between the CHIKV virus load and clinical symptoms of the CHIKV infection so that better patient management can be done in the background of the CHIKV outbreak as there is no licensed anti-viral drug and approved vaccines available against CHIKV.Methods:CHIKV RTPCR positive samples(n=18)(Acute febrile patients having D.O.F≤7 days)were taken for the quantification of CHIKV viremia by Real-Time PCR.Clinical features of the febrile patients were recorded during the collection of blood samples.Results:The log mean virus load of 18 RT-PCR-positive samples was 1.3×10^(6) copies/mL(1.21×10^(3)–2.33×10^(8) copies/mL).Among the observed clinical features,the log mean virus load(CHIKV)of the patients without skin rash is higher than in the patients with skin rash(6.61 vs.5.5,P=0.0435).Conclusion:The conclusion of the study was that the patients with skin rashes had lower viral load and those without skin rashes had higher viral load.
文摘Rationale:Transmitted to humans via the Aedes mosquito,Chikungunya virus(CHIKV)is associated with multi-system complications,sometimes collectively referred to as“atypical features.”However,a disorder of the nervous system appears to be the most common severe complication of CHIKV infection.Patient’s Concern:A seventy-five-year-old patient from India presented to the hospital with fever,chills,rigors,and multiple joint pains for which he was worked up.Diagnosis:CHIKV encephalitis.Interventions:The patient was treated initially on supportive therapy with antipyretics,intravenous fluids;however,during his hospital stay,the patient had altered sensorium during which he was managed in the intensive care unit;required mechanical ventilation.Outcomes:The patient sccumbed to his illness.Lessons:Treating clinicians should keep CHIKV disease in the differential diagnosis in cases of febrile exanthems associated with disabling arthritis,especially in a CHIKV-endemic country like India.
文摘As a matter of fact, infectious diseases hamper everyone’s life and produce a lifelong threat to everyone neutral of age, sex, lifestyle and socio-economic status. Nowadays, come into the sight of Chikungunya viral (CHIKV) infection injured many Asian and African countries, also deliberated threat in rising countries and also low socio-economic countries. CHIKV is a positive-sense, enveloped single-stranded, RNA virus belonging to the genus Alphavirus, family Togaviridae. As the Dengue & Chikungunya viruses are spread simultaneously at the same time, so it is tough to identify them. In our resource-limited countries, swift detection of CHIKV by RT-LAMP is the simplest molecular technique in low-equipment settings without the use of any expensive decoration. Heat-treated centrifuged and uncentrifuged samples were used in this study and they showed the same result (100%). Different instruments like heat block, water bath, conventional thermal cycler & real-time thermal cycler were used to amplify the CHIKV RNA and they indicated that 100% samples were identified by all four instruments. The amplified products were visualized by turbidity test, color change by HNB, step-ladder band pattern in agarose gel electrophoresis and amplification curve in real-time thermal cycler naked eye, here the results also showed 100% samples were determined by all visualized methods. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a recent technique for amplifying RNA under limited temperature, with high tangibility, quickness and competency. To identify the CHIKV RNA Reverse transcription loop-mediated isothermal amplification was fabricated and validated, and the results were also compared with reverse transcription polymerase chain reaction (RT-PCR). The sensitivity was 95.71% and specificity was 100%, these results indicate that RT-LAMP is a feasible method for quick detection of CHIKV RNA.
文摘目的对1例缅甸输入基孔肯雅热病例血清标本进行病毒分离及全基因组测序,分析其基因特征。方法采用real-time RT-PCR方法对标本进行检测,分离培养后获得毒株,对病毒核酸扩增后的产物进行全基因组测序,使用DNAStar 7.1软件对测序结果进行拼接,Mega5.0软件对序列进行比对和系统发生树构建。结果病例血清标本核酸检测显示CHIKV阳性,经分离培养获得CHIKV毒株(YN0627株),全基因组测序得到其序列,YN0627全长为11586 nt,其基因结构符合CHIKV的基因特征。系统进化分析显示,YN0627与东中南非洲遗传谱系(East,Central and South African Lineage,ECSA)的其他流行株聚集在一起,属于ECSA谱系。YN0627的编码区与参考序列相比,核苷酸同源性为85.24%~99.96%,氨基酸同源性为95.34%~99.97%,结构蛋白编码区域有28个氨基酸变异位点。结论云南省输入性CHIKV-YN0627属于ECSA谱系,且观察到多个氨基酸位点突变,提示云南省应当加强对CHIKV的监测和研究。
文摘Chikungunva virus is a mosquito-transmitted alphavirus that causes chikungunva fever,a febrile illness associated with severe arthralgia and rash.Chikungunva virus is transmitted by culicine mosquitoes:Chikungunya virus replicates in the skin,disseminates to liver,muscle,joints.lymphoid tissue and brain,presumably through the blood.Phylogenetic studies showed that the Indian Ocean and the Indian subcontinent epidemics were caused by two different introductions of distinct strains of East/Central/South African genotype of CHIKV.The paraphyletic grouping of African CHIK viruses supports the historical evidence that the virus was introduced into Asia from Africa.Phylogenetic analysis divided Chikungunva virus isolates into three distinct genotypes based on geographical origins:the first,the West Africa genotype,consisted of isolates from Senegal and Nigeria;the second contained strains from East/Central/South African genotype,while the third contained solely Asian.The most recent common ancestor for the recent epidemic,which ravaged Indian Ocean islands and Indian subcontinent in 2004- 2007.was found to date in 2002.Asian lineage dated about 1952 and exhibits similar spread patterns of the recent Indian Ocean outbreak lineage,with successive epidemics detected along an eastward path.Asian group splitted into two clades:an Indian lineage and a south east lineage.Outbreaks of Chikungunya virus fever in Asia have not been associated necessarily with outbreaks in Africa.Phylogenetic tools can reconstruct geographic spread of Chikungunva virus during the epidemics wave.The good management of patients with acute Chikungunva virus infection is essential for public health in susceptible areas with current Aedes spp activity.
基金supported in part by the National Key Program Project Grant from MOST #2016YFC1201000
文摘Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America suddenly, causing major regional epidemics recently and becoming a notable global health problem. Infection by CHIKV results in a spectrum of clinical diseases including an acute self-limiting febrile illness in most individuals, a chronic phase of recurrent join pain in a proportion of patients, and long-term arthralgia for months to years for the unfortunate few. No specific anti-viral drugs or licensed vaccines for CHIKV are available so far. A better understanding of virus-host interactions is essential for the development of therapeutics and vaccines. To this end, we reviewed the existing knowledge on CHIKV's epidemiology, clinical presentation, molecular virology, diagnostic approaches, host immune response, vaccine development, and available animal models. Such a comprehensive overview, we believe, will shed lights on the promises and challenges in CHIKV vaccine development.
