Severe fever with thrombocytopenia syndrome(SFTS)caused by the SFTS virus(SFTSV)is an emerging disease in East Asia with a fatality rate of up to 30%.However,the viral-host interaction of SFTSV remains largely unknown...Severe fever with thrombocytopenia syndrome(SFTS)caused by the SFTS virus(SFTSV)is an emerging disease in East Asia with a fatality rate of up to 30%.However,the viral-host interaction of SFTSV remains largely unknown.The heat-shock protein 90(Hsp90)family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many viruses.Here,we showed that Hsp90 is an important host factor involved in SFTSV infection.Hsp90 inhibitors significantly reduced SFTSV replication,viral protein expression,and the formation of inclusion bodies consisting of nonstructural proteins(NSs).Among viral proteins,NSs appeared to be the most reduced when Hsp90 inhibitors were used,and further analysis showed that their translation was affected.Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90βspecifically interacted with them.Knockdown of Hsp90βexpression also inhibited replication of SFTSV.These results suggest that Hsp90βplays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS.展开更多
Severe fever with thrombocytopenia syndrome(SFTS)is an emerging hemorrhagic fever disease caused by SFTSV,a newly discovered phlebovirus that is named after the disease.Currently,no effective vaccines or drugs are ava...Severe fever with thrombocytopenia syndrome(SFTS)is an emerging hemorrhagic fever disease caused by SFTSV,a newly discovered phlebovirus that is named after the disease.Currently,no effective vaccines or drugs are available for use against SFTSV infection,as our understanding of the viral pathogenesis is limited.Bortezomib(PS-341),a dipeptideboronic acid analog,is the first clinically approved proteasome inhibitor for use in humans.In this study,the antiviral efficacy of PS-341 against SFTSV infection was tested in human embryonic kidney HEK293T(293T)cells.We employed four different assays to analyze the antiviral ability of PS-341 and determined that PS-341 inhibited the proliferation of SFTSV in 293T cells under various treatment conditions.Although PS-341 did not affect the virus absorption,PS-341 treatment within a non-toxic concentration range resulted in a significant reduction of progeny viral titers in infected cells.Dual-luciferase reporter assays and Western blot analysis revealed that PS-341 could reverse the SFTSV-encoded nonstructural protein(NS)mediated degradation of retinoic acid-inducible gene-1(RIG-I),thereby antagonizing the inhibitory effect of NSs on interferons and blocking virus replication.In addition,we observed that inhibition of apoptosis promotes virus replication.These results indicate that targeting of cellular interferon pathways and apoptosis during acute infection might serve as the bases of future therapeutics for the treatment of SFTSV infections.展开更多
SFTS virus(SFTSV)is a novel bunyavirus,which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome(SFTS)in China in 2009,and was now prevalent in at least 25 provinces in China.SFTS wa...SFTS virus(SFTSV)is a novel bunyavirus,which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome(SFTS)in China in 2009,and was now prevalent in at least 25 provinces in China.SFTS was subsequently identified in South Korea and Japan in 2012.To explore themolecular evolution and genetic characteristics of this newly identified pathogen,we reported 72 whole genome sequences of SFTSV,and built a dataset of SFTSV genome sequences containing 292 L-segment,302 M-segment and 502 S-segment.We clearly divided SFTSV into six genotypes,Genotype A-F.It was found that genotype F was the dominant epidemic genotype of Japan,South Korea,and Zhejiang province of China.The coalescent analysis supported that SFTSV originated in the early 18th century from Zhejiang province,and Genotype F was the most primitive one.Henan,Hubei,and Anhui provinces which are located in Dabie Mountain area weremainly epidemic of Genotype A,which emerged relatively late but distributed widely.A total of 37 recombination events were identified,making SFTSV with a high recombination frequency(L segment 5.1%,Msegment 3.6%,S segment 0.8%)among negative-strand segmented RNA viruses.It was identified that 19 reassortant strains belonged to 12 reassortment forms of SFTSV genome containing 6 newly identified forms.The reassortment virus and recombination in tick were both found for the first time.We also found many of genotype-specific mutation sites,7 of which could be considered as potential molecular marker for genotype classification.This study promoted a more comprehensive understanding of the phylogeny and origin,and the genetic diversity of SFTSV,and it could help the studies of other newly discovered tick-borne bunyavirus as reference data and research ideas.展开更多
Severe fever with thrombocytopenia syndrome virus(SFTSV)is an emerging tick-borne bunyavirus that causes hemorrhagic fever-like disease(SFTS)in humans with a case fatality rate up to 30%.To date,the molecular biology ...Severe fever with thrombocytopenia syndrome virus(SFTSV)is an emerging tick-borne bunyavirus that causes hemorrhagic fever-like disease(SFTS)in humans with a case fatality rate up to 30%.To date,the molecular biology involved in SFTSV infection remains obscure.There are seven major genotypes of SFTSV(C1-C4 and J1-J3)and previously a reverse genetic system was established on a C3 strain of SFTSV.Here,we reported successfully establishment of a reverse genetics system based on a SFTSV C4 strain.First,we obtained the 5’-and 3’-terminal untranslated region(UTR)sequences of the Large(L),Medium(M)and Small(S)segments of a laboratory-adapted SFTSV C4 strain through rapid amplification of cDNA ends analysis,and developed functional T7 polymerase-based L-,M-and S-segment minigenome assays.Then,fulllength cDNA clones were constructed and infectious SFTSV were recovered from co-transfected cells.Viral infectivity,growth kinetics,and viral protein expression profile of the rescued virus were compared with the laboratory-adapted virus.Focus formation assay showed that the size and morphology of the foci formed by the rescued SFTSV were indistinguishable with the laboratory-adapted virus.However,one-step growth curve and nucleoprotein expression analyses revealed the rescued virus replicated less efficiently than the laboratory-adapted virus.Sequence analysis indicated that the difference may be due to the mutations in the laboratory-adapted strain which are more prone to cell culture.The results help us to understand the molecular biology of SFTSV,and provide a useful tool for developing vaccines and antivirals against SFTS.展开更多
Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in humans.The molecular m...Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in humans.The molecular mechanisms and host cellular factors required for SFTSV infection remain uncharacterized.Using a genome-wide CRISPR-based screening strategy,we identified a host cellular protein,sorting nexin 11(SNX11)which is involved in the intracellular endosomal trafficking pathway,as an essential cell factor for SFTSV infection.An SNX11-KO HeLa cell line was established,and SFTSV replication was significantly reduced.The glycoproteins of SFTSV were detected and remained in later endosomal compartments but were not detectable in the endoplasmic reticulum(ER)or Golgi apparatus.pH values in the endosomal compartments of the SNX11-KO cells increased compared with the pH of normal HeLa cells,and lysosomal-associated membrane protein 1(LAMP1)expression was significantly elevated in the SNX11-KO cells.Overall,these results indicated that penetration of SFTSV from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking SNX11.Our study for the first time provides insight into the important role of the SNX11 as an essential host factor in the intracellular trafficking and penetrating process of SFTSV infection via potential regulation of viral protein sorting,membrane fusion,and other endocytic machinery.展开更多
Severe fever with thrombocytopenia syndrome virus(SFTSV),the causative agent of a febrile human disease,was first identified from central and eastern provinces in China,and later in Japan and South Korea.Hubei Provinc...Severe fever with thrombocytopenia syndrome virus(SFTSV),the causative agent of a febrile human disease,was first identified from central and eastern provinces in China,and later in Japan and South Korea.Hubei Province is one of the major SFTS epidemic areas in the central part of China.This study reported the isolation of 11 new SFTSV strains from patients in Hubei Province collected in 2017.Extensive phylogenetic analyses were conducted based on the complete coding sequences of SFTSV segments including the new strains.It was suggested that five different SFTSV genotypes were circulating in Hubei,and 15 reassortment patterns and migration pathways correlated with each genotype were identified,which was more than previously recognized.Hubei Province was more involved in the evolutionary events of SFTSV than that previously thought in which the evolutionary events of SFTSV were reported to be independent from those in other epidemic regions.Further divergence of SFTSV strains was suggested by pairwise comparison of SFTSV sequences from each genotype and sequence identity normalized to representative strain in genotype C1.Subsequently,amino acid variations specific for genotype(s),strain(s),or cluster(s)were inspected,which may be related to differential biological activity of SFTSV strains/genotypes.In conclusion,we analyzed the current status of SFTSV phylogeny in Hubei Province and discussed the possible events correlated to SFTSV evolution.It provided an in-depth insight into SFTSV evolution,raising concerns for the use of proper SFTSV strains in future studies.展开更多
Severe fever with thrombocytopenia syndrome(SFTS)is an emerging infectious disease with high mortality(12%–30%).The mechanism by which the SFTS bunyavirus(SFTSV)causes severe illness remains unclear.To evaluate the p...Severe fever with thrombocytopenia syndrome(SFTS)is an emerging infectious disease with high mortality(12%–30%).The mechanism by which the SFTS bunyavirus(SFTSV)causes severe illness remains unclear.To evaluate the phenotypic and functional characteristics of the NK cell subsets in SFTS patients,twenty-nine SFTS patients were sequentially sampled from admission until recovery.Phenotypic and functional characteristics of NK cell subsets in circulating blood were analysed via flow cytometry.Then,correlations between NK cell subset frequencies and the SFTS index(SFTSI)were evaluated in all SFTS patients(15 mild,14 severe)upon admission.The frequencies of CD56dimCD16+NK cells were greatly decreased in early SFTSV infection and were negatively correlated with disease severity.Additionally,higher Ki-67 and granzyme B expression and relatively lower NKG2 A expression in CD56dimCD16+NK cells were observed in acute infection.Moreover,the effector function of CD56dimNK cells was increased in the acute phase compared with the recovery phase in nine severe SFTS patients.Additionally,interleukin(IL)-15,interferon(IFN)-a,IL-18 and IFN-c secretion was markedly increased during early infection.Collectively,despite depletion of CD56dimCD16+NK cells,activation and functional enhancement of CD56dimCD16+NK cells were still observed,suggesting their involvement in defence against early SFTSV infection.展开更多
Severe fever with thrombocytopenia syndrome(SFTS),caused by SFTS virus(SFTSV)infection,was first reported in 2010 in China with an initial fatality of up to 30%.The laboratory confirmation of SFTSV infection in terms ...Severe fever with thrombocytopenia syndrome(SFTS),caused by SFTS virus(SFTSV)infection,was first reported in 2010 in China with an initial fatality of up to 30%.The laboratory confirmation of SFTSV infection in terms of detection of viral RNA or antibody levels is critical for SFTS diagnosis and therapy.In this study,a new luciferase immunoprecipitation system(LIPS)assay based on p REN2 plasmid expressing SFTSV NP gene and tagged with Renilla luciferase(Rluc),was established and used to investigate the levels of antibody responses to SFTSV.Totally 464 serum samples from febrile patients were collected in the hospital of Shaoxing City in Zhejiang Province in 2019.The results showed that 82 of the 464 patients(17.7%)had antibody response to SFTSV,which were further supported by immunofluorescence assays(IFAs).Further,q RT-PCR and microneutralization tests showed that among the 82 positive cases,15 patients had viremia,10 patients had neutralizing antibody,and one had both(totally 26 patient).However,none of these patients were diagnosed as SFTS in the hospital probably because of their mild symptoms or subclinical manifestations.All the results indicated that at least the 26 patients having viremia or neutralizing antibody were the missed diagnosis of SFTS cases.The findings suggested the occurrence of SFTS and the SFTS incidence were higher than the reported level in Shaoxing in 2019,and that LIPS may provide an alternative strategy to confirm SFTSV infection in the laboratory.展开更多
Background:Severe fever with thrombocytopenia syndrome(SFTS)is a newly identified emerging infectious disease,which is caused by a novel bunyavirus(termed SFTSV)in Asia.Although mosquitoes have not been identified as ...Background:Severe fever with thrombocytopenia syndrome(SFTS)is a newly identified emerging infectious disease,which is caused by a novel bunyavirus(termed SFTSV)in Asia.Although mosquitoes have not been identified as the primary vectors,as revealed by epidemiological surveys,their role in transmitting this SFTSV as a suspicious vector has not been validated.Findings:In this study,we conducted experimental infections of mosquitoes with SFTSV to examine the role of mosquitoes in the transmission of the virus.We did not detect viral replication in Culex pipiens pallens,Aedes aegyptis and Anopheles sinensis as revealed by qRT-PCR assay.In addition,we failed to isolate SFTSV from the Vero cells cultured with suspensions of SFTSV-infected mosquitoes.Conclusion:The results of the present study demonstrate little possibility that mosquitoes act as vectors for the emerging pathogen SFTSV.展开更多
基金supported by grants from the National Natural Science Foundation of China(31900146)the key Biosafety Science and Technology Program of Hubei Jiangxia Laboratory(JXBS001)+1 种基金the Hubei Natural Science Foundation for Distinguished Young Scholars(2021CFA050)the Creative Research Group Program of Natural Science Foundation of Hubei Province(2022CFA021).
文摘Severe fever with thrombocytopenia syndrome(SFTS)caused by the SFTS virus(SFTSV)is an emerging disease in East Asia with a fatality rate of up to 30%.However,the viral-host interaction of SFTSV remains largely unknown.The heat-shock protein 90(Hsp90)family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many viruses.Here,we showed that Hsp90 is an important host factor involved in SFTSV infection.Hsp90 inhibitors significantly reduced SFTSV replication,viral protein expression,and the formation of inclusion bodies consisting of nonstructural proteins(NSs).Among viral proteins,NSs appeared to be the most reduced when Hsp90 inhibitors were used,and further analysis showed that their translation was affected.Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90βspecifically interacted with them.Knockdown of Hsp90βexpression also inhibited replication of SFTSV.These results suggest that Hsp90βplays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS.
基金supported by the National Science Foundation of China (31270201)the National Key Research and Development Program of China (2017YFA0205102)+1 种基金the Seed Foundation of Tianjin University (2014XRX-0026)the National Science Foundation of Tianjin (No.16JCQNJC09800)
文摘Severe fever with thrombocytopenia syndrome(SFTS)is an emerging hemorrhagic fever disease caused by SFTSV,a newly discovered phlebovirus that is named after the disease.Currently,no effective vaccines or drugs are available for use against SFTSV infection,as our understanding of the viral pathogenesis is limited.Bortezomib(PS-341),a dipeptideboronic acid analog,is the first clinically approved proteasome inhibitor for use in humans.In this study,the antiviral efficacy of PS-341 against SFTSV infection was tested in human embryonic kidney HEK293T(293T)cells.We employed four different assays to analyze the antiviral ability of PS-341 and determined that PS-341 inhibited the proliferation of SFTSV in 293T cells under various treatment conditions.Although PS-341 did not affect the virus absorption,PS-341 treatment within a non-toxic concentration range resulted in a significant reduction of progeny viral titers in infected cells.Dual-luciferase reporter assays and Western blot analysis revealed that PS-341 could reverse the SFTSV-encoded nonstructural protein(NS)mediated degradation of retinoic acid-inducible gene-1(RIG-I),thereby antagonizing the inhibitory effect of NSs on interferons and blocking virus replication.In addition,we observed that inhibition of apoptosis promotes virus replication.These results indicate that targeting of cellular interferon pathways and apoptosis during acute infection might serve as the bases of future therapeutics for the treatment of SFTSV infections.
基金supported by the National Major Science and Technol-ogy Project of China(2018ZX10711001,2016ZX10004222-002)。
文摘SFTS virus(SFTSV)is a novel bunyavirus,which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome(SFTS)in China in 2009,and was now prevalent in at least 25 provinces in China.SFTS was subsequently identified in South Korea and Japan in 2012.To explore themolecular evolution and genetic characteristics of this newly identified pathogen,we reported 72 whole genome sequences of SFTSV,and built a dataset of SFTSV genome sequences containing 292 L-segment,302 M-segment and 502 S-segment.We clearly divided SFTSV into six genotypes,Genotype A-F.It was found that genotype F was the dominant epidemic genotype of Japan,South Korea,and Zhejiang province of China.The coalescent analysis supported that SFTSV originated in the early 18th century from Zhejiang province,and Genotype F was the most primitive one.Henan,Hubei,and Anhui provinces which are located in Dabie Mountain area weremainly epidemic of Genotype A,which emerged relatively late but distributed widely.A total of 37 recombination events were identified,making SFTSV with a high recombination frequency(L segment 5.1%,Msegment 3.6%,S segment 0.8%)among negative-strand segmented RNA viruses.It was identified that 19 reassortant strains belonged to 12 reassortment forms of SFTSV genome containing 6 newly identified forms.The reassortment virus and recombination in tick were both found for the first time.We also found many of genotype-specific mutation sites,7 of which could be considered as potential molecular marker for genotype classification.This study promoted a more comprehensive understanding of the phylogeny and origin,and the genetic diversity of SFTSV,and it could help the studies of other newly discovered tick-borne bunyavirus as reference data and research ideas.
基金supported by grants from the National Natural Science Foundation of China(No.31900146Open Research Fund Program of the State Key Laboratory of Virology of China(No.2020IOV003)Team project of Health Commission of Hubei Province(WJ2019C003)。
文摘Severe fever with thrombocytopenia syndrome virus(SFTSV)is an emerging tick-borne bunyavirus that causes hemorrhagic fever-like disease(SFTS)in humans with a case fatality rate up to 30%.To date,the molecular biology involved in SFTSV infection remains obscure.There are seven major genotypes of SFTSV(C1-C4 and J1-J3)and previously a reverse genetic system was established on a C3 strain of SFTSV.Here,we reported successfully establishment of a reverse genetics system based on a SFTSV C4 strain.First,we obtained the 5’-and 3’-terminal untranslated region(UTR)sequences of the Large(L),Medium(M)and Small(S)segments of a laboratory-adapted SFTSV C4 strain through rapid amplification of cDNA ends analysis,and developed functional T7 polymerase-based L-,M-and S-segment minigenome assays.Then,fulllength cDNA clones were constructed and infectious SFTSV were recovered from co-transfected cells.Viral infectivity,growth kinetics,and viral protein expression profile of the rescued virus were compared with the laboratory-adapted virus.Focus formation assay showed that the size and morphology of the foci formed by the rescued SFTSV were indistinguishable with the laboratory-adapted virus.However,one-step growth curve and nucleoprotein expression analyses revealed the rescued virus replicated less efficiently than the laboratory-adapted virus.Sequence analysis indicated that the difference may be due to the mutations in the laboratory-adapted strain which are more prone to cell culture.The results help us to understand the molecular biology of SFTSV,and provide a useful tool for developing vaccines and antivirals against SFTS.
基金supported by the National Key Project for Infectious Disease from the Ministry of Science and Technology (Grant No. 2018ZX10711-001)
文摘Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in humans.The molecular mechanisms and host cellular factors required for SFTSV infection remain uncharacterized.Using a genome-wide CRISPR-based screening strategy,we identified a host cellular protein,sorting nexin 11(SNX11)which is involved in the intracellular endosomal trafficking pathway,as an essential cell factor for SFTSV infection.An SNX11-KO HeLa cell line was established,and SFTSV replication was significantly reduced.The glycoproteins of SFTSV were detected and remained in later endosomal compartments but were not detectable in the endoplasmic reticulum(ER)or Golgi apparatus.pH values in the endosomal compartments of the SNX11-KO cells increased compared with the pH of normal HeLa cells,and lysosomal-associated membrane protein 1(LAMP1)expression was significantly elevated in the SNX11-KO cells.Overall,these results indicated that penetration of SFTSV from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking SNX11.Our study for the first time provides insight into the important role of the SNX11 as an essential host factor in the intracellular trafficking and penetrating process of SFTSV infection via potential regulation of viral protein sorting,membrane fusion,and other endocytic machinery.
基金supported by the National Key R&D Programme of China(2018ZX10734404-010)the Nature Science Foundation of Hubei Province(2019CFB790 and 2018CFB471)+2 种基金the Innovation Team Project of Hubei Provincial Health Commission(WJ2019C003)the Open Research Fund of State Key Laboratory of Virology(2018IOV004)the Special Project of Technical Conditions(2060503)。
文摘Severe fever with thrombocytopenia syndrome virus(SFTSV),the causative agent of a febrile human disease,was first identified from central and eastern provinces in China,and later in Japan and South Korea.Hubei Province is one of the major SFTS epidemic areas in the central part of China.This study reported the isolation of 11 new SFTSV strains from patients in Hubei Province collected in 2017.Extensive phylogenetic analyses were conducted based on the complete coding sequences of SFTSV segments including the new strains.It was suggested that five different SFTSV genotypes were circulating in Hubei,and 15 reassortment patterns and migration pathways correlated with each genotype were identified,which was more than previously recognized.Hubei Province was more involved in the evolutionary events of SFTSV than that previously thought in which the evolutionary events of SFTSV were reported to be independent from those in other epidemic regions.Further divergence of SFTSV strains was suggested by pairwise comparison of SFTSV sequences from each genotype and sequence identity normalized to representative strain in genotype C1.Subsequently,amino acid variations specific for genotype(s),strain(s),or cluster(s)were inspected,which may be related to differential biological activity of SFTSV strains/genotypes.In conclusion,we analyzed the current status of SFTSV phylogeny in Hubei Province and discussed the possible events correlated to SFTSV evolution.It provided an in-depth insight into SFTSV evolution,raising concerns for the use of proper SFTSV strains in future studies.
基金supported by the National Natural Science Foundation of China(81271884)and of Hubei(2018CFB471)
文摘Severe fever with thrombocytopenia syndrome(SFTS)is an emerging infectious disease with high mortality(12%–30%).The mechanism by which the SFTS bunyavirus(SFTSV)causes severe illness remains unclear.To evaluate the phenotypic and functional characteristics of the NK cell subsets in SFTS patients,twenty-nine SFTS patients were sequentially sampled from admission until recovery.Phenotypic and functional characteristics of NK cell subsets in circulating blood were analysed via flow cytometry.Then,correlations between NK cell subset frequencies and the SFTS index(SFTSI)were evaluated in all SFTS patients(15 mild,14 severe)upon admission.The frequencies of CD56dimCD16+NK cells were greatly decreased in early SFTSV infection and were negatively correlated with disease severity.Additionally,higher Ki-67 and granzyme B expression and relatively lower NKG2 A expression in CD56dimCD16+NK cells were observed in acute infection.Moreover,the effector function of CD56dimNK cells was increased in the acute phase compared with the recovery phase in nine severe SFTS patients.Additionally,interleukin(IL)-15,interferon(IFN)-a,IL-18 and IFN-c secretion was markedly increased during early infection.Collectively,despite depletion of CD56dimCD16+NK cells,activation and functional enhancement of CD56dimCD16+NK cells were still observed,suggesting their involvement in defence against early SFTSV infection.
基金supported by the National Program on Key Research Project of China(2018YFE0200400,2019YFC1200700)the National Natural Science Foundation of China(U20A20135)+1 种基金the Strategic Biological Resources Capacity Building Project of Chinese Academy of Sciences(KFJ-BRP-017-06)the Key deployment projects of Chinese Academy of Sciences(KJZD-SW-L11)
文摘Severe fever with thrombocytopenia syndrome(SFTS),caused by SFTS virus(SFTSV)infection,was first reported in 2010 in China with an initial fatality of up to 30%.The laboratory confirmation of SFTSV infection in terms of detection of viral RNA or antibody levels is critical for SFTS diagnosis and therapy.In this study,a new luciferase immunoprecipitation system(LIPS)assay based on p REN2 plasmid expressing SFTSV NP gene and tagged with Renilla luciferase(Rluc),was established and used to investigate the levels of antibody responses to SFTSV.Totally 464 serum samples from febrile patients were collected in the hospital of Shaoxing City in Zhejiang Province in 2019.The results showed that 82 of the 464 patients(17.7%)had antibody response to SFTSV,which were further supported by immunofluorescence assays(IFAs).Further,q RT-PCR and microneutralization tests showed that among the 82 positive cases,15 patients had viremia,10 patients had neutralizing antibody,and one had both(totally 26 patient).However,none of these patients were diagnosed as SFTS in the hospital probably because of their mild symptoms or subclinical manifestations.All the results indicated that at least the 26 patients having viremia or neutralizing antibody were the missed diagnosis of SFTS cases.The findings suggested the occurrence of SFTS and the SFTS incidence were higher than the reported level in Shaoxing in 2019,and that LIPS may provide an alternative strategy to confirm SFTSV infection in the laboratory.
基金This work was supported by:the National Natural Science Foundation of China(81373055)Science&Technology Demonstration Project for Emerging Infectious Diseases Control and Prevention(BE2015714)The key discipline of epidemic(ZDXKA2016008)。
文摘Background:Severe fever with thrombocytopenia syndrome(SFTS)is a newly identified emerging infectious disease,which is caused by a novel bunyavirus(termed SFTSV)in Asia.Although mosquitoes have not been identified as the primary vectors,as revealed by epidemiological surveys,their role in transmitting this SFTSV as a suspicious vector has not been validated.Findings:In this study,we conducted experimental infections of mosquitoes with SFTSV to examine the role of mosquitoes in the transmission of the virus.We did not detect viral replication in Culex pipiens pallens,Aedes aegyptis and Anopheles sinensis as revealed by qRT-PCR assay.In addition,we failed to isolate SFTSV from the Vero cells cultured with suspensions of SFTSV-infected mosquitoes.Conclusion:The results of the present study demonstrate little possibility that mosquitoes act as vectors for the emerging pathogen SFTSV.
