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
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
Chikungunya virus(CHIKV)is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain.To better understand how CHIKV rewires the host cell and usurps host cell functions,we generated a systematic CHIKV...Chikungunya virus(CHIKV)is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain.To better understand how CHIKV rewires the host cell and usurps host cell functions,we generated a systematic CHIKV-human protein-protein interaction map and revealed several novel connections that will inform further mechanistic studies.One of these novel interactions,between the viral protein E1 and STIP1 homology and U-box containing protein 1(STUB1),was found to mediate ubiquitination of E1 and degrade E1 through the proteasome.Capsid associated with G3BP1,G3BP2 and AAAþATPase valosin-containing protein(VCP).Furthermore,VCP inhibitors blocked CHIKV infection,suggesting VCP could serve as a therapeutic target.Further work is required to fully understand the functional consequences of these interactions.Given that CHIKV proteins are conserved across alphaviruses,many virus-host protein-protein interactions identified in this study might also exist in other alphaviruses.Construction of interactome of CHIKV provides the basis for further studying the function of alphavirus biology.展开更多
The chikungunya virus(CHIKV) is a mosquito-transmitted alphavirus, which has infected millions of people in Africa, Asia, Americas, and Europe since it reemerged in India and Indian Ocean regions in 2005–2006. Starti...The chikungunya virus(CHIKV) is a mosquito-transmitted alphavirus, which has infected millions of people in Africa, Asia, Americas, and Europe since it reemerged in India and Indian Ocean regions in 2005–2006. Starting in the middle of November 2016, CHIKV has been widely spread, and more than 4,000 cases of infections in humans were confirmed in Pakistan. Here, we report the first isolation and characterization of CHIKV from the Pakistan outbreak. Eight CHIKV strains were newly isolated from human serum samples using a cell culture procedure. A full-length genome sequence and eight complete envelope(E1) sequences of CHIKV from Pakistan were obtained in this study. Alignment of the CHIKV E1 sequences revealed that the eight new CHIKV isolates were highly homogeneous, with only two nonsynonymous substitutions found at generally conserved sites(E99 and Q235). Based on the comparison of 342 E1 sequences, the two nonsynonymous mutations were located in well-recognized domains associated with viral functions such as the cell fusion and vector specificity, suggesting their potential functional importance. Phylogenetic analysis indicated that the CHIKV strains from Pakistan originated from CHIKV circulating in the Indian region. This study helps elucidate the epidemics of CHIKV in Pakistan and also provides a foundation for studies of evolution and expansion of CHIKV in South Asia.展开更多
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
Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical ...Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical use.Here,we developed an m RNA-lipid nanoparticle(m RNA-LNP)vaccine expressing CHIKV E2-E1 antigen,and compared its immunogenicity with soluble recombinant protein s E2-E1 antigen expressed in S2 cells.For comparison,we first showed that recombinant protein antigens mixed with aluminum adjuvant elicit strong antigenspecific humoral immune response and a moderate cellular immune response in C57BL/6 mice.Moreover,s E2-E1vaccine stimulated 12-23 folds more neutralizing antibodies than s E1 vaccine and s E2 vaccine.Significantly,when E2-E1 gene was delivered by an m RNA-LNP vaccine,not only the better magnitude of neutralizing antibody responses was induced,but also greater cellular immune responses were generated,especially for CD8+T cell responses.Moreover,E2-E1-LNP induced CD8~+T cells can perform cytotoxic effect in vivo.Considering its better immunogenicity and convenience of preparation,we suggest that more attention should be placed to develop CHIKV E2-E1-LNP m RNA vaccine.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
Chikungunya virus(CHIKV) is a mosquito-borne alphavirus. As an emerging virus, CHIKV imposes a threat to public health. Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. L...Chikungunya virus(CHIKV) is a mosquito-borne alphavirus. As an emerging virus, CHIKV imposes a threat to public health. Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. Lycorine, an alkaloid from Amaryllidaceae plants, has antiviral activity against a number of viruses such as coronavirus, flavivirus and enterovirus. In this study, we found that lycorine could inhibit CHIKV in cell culture at a concentration of 10 lmol/L without apparent cytotoxicity. In addition, it exhibited broad-spectrum anti-alphavirus activity, including Sindbis virus(SINV),Semliki Forest virus(SFV), and Venezuelan equine encephalomyelitis virus(VEEV). The time of addition studies indicated that lycorine functions at an early post-entry stage of CHIKV life cycle. The results based on two different CHIKV replicons provided further evidence that lycorine exerts its antiviral activity mainly by inhibiting CHIKV translation.Overall, our study extends the antiviral spectrum of lycorine.展开更多
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.
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 National Natural Science Foundation of China (82072270 and 82272306)Taishan Scholars Program (tstp20221142)+1 种基金Shandong Provincial Natural Science Foundation (ZR2021QC095)Academic Promotion Programme of Shandong First Medical University (2019LJ001).
文摘Chikungunya virus(CHIKV)is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain.To better understand how CHIKV rewires the host cell and usurps host cell functions,we generated a systematic CHIKV-human protein-protein interaction map and revealed several novel connections that will inform further mechanistic studies.One of these novel interactions,between the viral protein E1 and STIP1 homology and U-box containing protein 1(STUB1),was found to mediate ubiquitination of E1 and degrade E1 through the proteasome.Capsid associated with G3BP1,G3BP2 and AAAþATPase valosin-containing protein(VCP).Furthermore,VCP inhibitors blocked CHIKV infection,suggesting VCP could serve as a therapeutic target.Further work is required to fully understand the functional consequences of these interactions.Given that CHIKV proteins are conserved across alphaviruses,many virus-host protein-protein interactions identified in this study might also exist in other alphaviruses.Construction of interactome of CHIKV provides the basis for further studying the function of alphavirus biology.
基金supported by International Cooperation on key Technologies of Biosafety along the China–Pakistan Economic Corridor(153B42KYSB20170004)Major State Basic Research Development Program(2013FY 113500)the National Natural Science Foundation of China(81572003 and 31600141)
文摘The chikungunya virus(CHIKV) is a mosquito-transmitted alphavirus, which has infected millions of people in Africa, Asia, Americas, and Europe since it reemerged in India and Indian Ocean regions in 2005–2006. Starting in the middle of November 2016, CHIKV has been widely spread, and more than 4,000 cases of infections in humans were confirmed in Pakistan. Here, we report the first isolation and characterization of CHIKV from the Pakistan outbreak. Eight CHIKV strains were newly isolated from human serum samples using a cell culture procedure. A full-length genome sequence and eight complete envelope(E1) sequences of CHIKV from Pakistan were obtained in this study. Alignment of the CHIKV E1 sequences revealed that the eight new CHIKV isolates were highly homogeneous, with only two nonsynonymous substitutions found at generally conserved sites(E99 and Q235). Based on the comparison of 342 E1 sequences, the two nonsynonymous mutations were located in well-recognized domains associated with viral functions such as the cell fusion and vector specificity, suggesting their potential functional importance. Phylogenetic analysis indicated that the CHIKV strains from Pakistan originated from CHIKV circulating in the Indian region. This study helps elucidate the epidemics of CHIKV in Pakistan and also provides a foundation for studies of evolution and expansion of CHIKV in South Asia.
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 following grants:the National Key R&D Program of China(Grant 2016YFC1201000 to X.J.)the Institute Fund of Shanghai Public Health Clinical Center(Grant KY-GW-2021-17 to ZH.L.)。
文摘Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical use.Here,we developed an m RNA-lipid nanoparticle(m RNA-LNP)vaccine expressing CHIKV E2-E1 antigen,and compared its immunogenicity with soluble recombinant protein s E2-E1 antigen expressed in S2 cells.For comparison,we first showed that recombinant protein antigens mixed with aluminum adjuvant elicit strong antigenspecific humoral immune response and a moderate cellular immune response in C57BL/6 mice.Moreover,s E2-E1vaccine stimulated 12-23 folds more neutralizing antibodies than s E1 vaccine and s E2 vaccine.Significantly,when E2-E1 gene was delivered by an m RNA-LNP vaccine,not only the better magnitude of neutralizing antibody responses was induced,but also greater cellular immune responses were generated,especially for CD8+T cell responses.Moreover,E2-E1-LNP induced CD8~+T cells can perform cytotoxic effect in vivo.Considering its better immunogenicity and convenience of preparation,we suggest that more attention should be placed to develop CHIKV E2-E1-LNP m RNA vaccine.
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。
基金This work was supported by the National Key Research and Development Program of China(2018YFA0507201)。
文摘Chikungunya virus(CHIKV) is a mosquito-borne alphavirus. As an emerging virus, CHIKV imposes a threat to public health. Currently, there are no vaccines or antivirals available for the prevention of CHIKV infection. Lycorine, an alkaloid from Amaryllidaceae plants, has antiviral activity against a number of viruses such as coronavirus, flavivirus and enterovirus. In this study, we found that lycorine could inhibit CHIKV in cell culture at a concentration of 10 lmol/L without apparent cytotoxicity. In addition, it exhibited broad-spectrum anti-alphavirus activity, including Sindbis virus(SINV),Semliki Forest virus(SFV), and Venezuelan equine encephalomyelitis virus(VEEV). The time of addition studies indicated that lycorine functions at an early post-entry stage of CHIKV life cycle. The results based on two different CHIKV replicons provided further evidence that lycorine exerts its antiviral activity mainly by inhibiting CHIKV translation.Overall, our study extends the antiviral spectrum of lycorine.
