Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegment...Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegmented RNA genome.Due to its high pathogenicity and lethality,LASV is considered as a priority threat to public health,with an estimated cases of 300,000 infections and 5000 deaths annually.LASV was first isolated and described as a clinical entity in 1969 in Lassa,Nigeria(Garry,2023).LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages,with each lineage predominately localized in specific countries.Although the research on LF has been carried out for decades since the pathogen first characterized,there is no approved antiviral drugs or vaccines for clinical use against LASV to date(Grant et al.,2023).One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4(BSL-4)facilities.In this letter,we describe isolation,and characterization of the LASV from the clinical samples.And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility,aiming to investigate new therapeutic strategies for LASV infection.展开更多
Acute respiratory tract infections(ARTIs)are among the leading causes of morbidity and mortality in children worldwide.Human adenovirus(HAdV)infections are estimated to account for at least 5%of pediatric ARTIs.The ci...Acute respiratory tract infections(ARTIs)are among the leading causes of morbidity and mortality in children worldwide.Human adenovirus(HAdV)infections are estimated to account for at least 5%of pediatric ARTIs.The circulated genotypes of HAdV and the correlation between genotype and clinical manifestations in Wuhan,China,before and after the complete relaxation of nonpharmaceutical interventions against severe acute respiratory syndrome coronavirus 2,remain unknown.Here,101 HAdV strains were isolated from throat swab samples collected from hospitalized children with ARTIs who tested positive for HAdV nucleic acid.Of these,sixty-six strains from 2022 to twenty-three strains from 2023 were successfully genotyped and subjected to phylogenetic analysis based on the hexon,penton base,and fiber genes.Six genotypes,B3,C1,C2,C5,C104,and C108 were identified.HAdV-B3(84.85%)was the most prevalent type in 2022,while HAdV-C(86.96%),including C1,C2,C108,and C104,was the most prevalent in 2023.These strains were phylogenetically related to strains from Japan,China,and the United States in recent years.When comparing clinical characteristics,pediatric patients infected with B3,C1,C2,C5,C104,or C108 exhibited similar clinical manifestations,primarily fever and cough,but varying interleukin(IL)-10 levels.In conclusion,from June 2022 to September 2023,the circulated genotypes of HAdV in Wuhan included B3,C1,C2,C108,C5,and C104.The endemic pattern of HAdV in Wuhan,China,shifted from species B as the dominant type in 2022 to species C in 2023.展开更多
Encephalomyocarditis virus(EMCV),a potential zoonotic pathogen,poses significant socioeconomic and public health challenges across various host species.Although EMCV rarely triggers severe clinical symptoms in humans,...Encephalomyocarditis virus(EMCV),a potential zoonotic pathogen,poses significant socioeconomic and public health challenges across various host species.Although EMCV rarely triggers severe clinical symptoms in humans,its widespread prevalence and unique biological characteristics underscore the need for continuous surveillance and the development of effective therapeutics and prophylactics.In this study,we evaluated the neutralizing effects of a monoclonal antibody derived from the spleens of mice immunized with EMCV virus-like particles(VLPs),both in vitro and in vivo.Using recombinant DNA technology,we engineered a baculovirus system to express EMCVs P12A and 3C,facilitating the production of VLPs in Sf9 cells.These VLPs serve as antigens to immunize mice,leading to the isolation of the monoclonal antibody 45G3.This antibody exhibited high specificity for EMCV confor-mational epitopes,excluding linear epitopes,and demonstrated potent in vitro neutralizing activity,with an IC50 of 0.01873μg/mL.Immunoelectron microscopy(IEM)revealed a strong direct interaction between the 45G3 antibody and EMCV particles.Virus adsorption inhibition assays demonstrated that 45G3 effectively blocked viral attachment,thereby preventing further infection of host cells.These findings further support the notion of a robust interaction between the virus and the antibody.Moreover,in vivo assessments revealed that 45G3 significantly reduced viral loads in treated mice and improved survival outcomes following EMCV exposure.Additionally,posttreatment analysis revealed reduced tissue damage and a markedly decreased inflammatory response in the brain,indicating that the 45G3 antibody effectively blocked viral infection,thereby mitigating tissue damage and enhancing survival.These findings position 45G3 as a promising candidate for EMCV management and provide a strong foundation for the future development of antiviral drugs targeting this widespread virus.展开更多
Adjustment of the sowing date is a widely used measure in rice production for adapting to high-temperature conditions.However,the impact of a delayed sowing date(DS)on rice quality may vary by variety and ecological c...Adjustment of the sowing date is a widely used measure in rice production for adapting to high-temperature conditions.However,the impact of a delayed sowing date(DS)on rice quality may vary by variety and ecological conditions.In this study,we conducted experiments using four different sowing dates,the conventional sowing date 1(CS1),CS2(10 d later than CS1),DS1(30 d later than CS1),and DS2(30 d later than CS2),and three rice varieties,i.e.,Yixiangyou 2115,Fyou 498,and Chuanyou 6203.This experiment was conducted at four sites in the Sichuan Basin in 2018 and 2019 to evaluate the infuence of DS on the pasting properties of rice,which are a proxy for the eating and cooking quality(ECQ).In DS1 and DS2,the rice had a signifcantly greater amylose content(AC)but a lower protein content(PC),peak viscosity(PKV),cool paste viscosity(CPV),and hot paste viscosity(HPV)than in CS1 and CS2.Moreover,except for CS2 and DS1 in 2018,DS1 and DS2 led to 2.15-11.19%reductions in breakdown viscosity(BDV)and 23.46-108.47%increases in setback viscosity(SBV).However,the infuence of DS on rice pasting properties varied by study site and rice variety.In 2019,DS1 and DS2 led to BDV reductions of 2.35-9.33,2.61-8.61,10.03-17.78,and 2.06-8.93%,and SBV increases of 2.32-60.93,63.74-144.24,55.46-91.63,and-8.28-65.37%at the Dayi,Anzhou,Nanbu,and Shehong(except for SBV in CS2 and DS1)sites,respectively.DS resulted in greater reductions in PKV,HPV,CPV,and BDV and greater increases in the AC and SBV for Yixiangyou 2115 than for Chuanyou 6203 and Fyou 498.The correlation analysis indicated that PKV and HPV were signifcantly and positively related to the mean,maximum,and minimum temperatures after heading.These temperatures must be greater than 25.9,31.2,and 22.3℃,respectively,to increase the relative BDV and reduce the relative SBV of rice,thereby enhancing ECQ.In conclusion,DS might contribute to a signifcant deterioration in ECQ in machine-transplanted rice in the Sichuan Basin.A mean temperature above 25.9℃ after heading is required to improve the ECQ of rice.展开更多
Crimean-Congo hemorrhagic fever(CCHF)is a hemorrhagic fever caused by infection with the CCHF virus(CCHFV)and has a mortality rate of up to 30%.Thrombocytopenia is a hallmark of CCHF;however,the mechanisms underlying ...Crimean-Congo hemorrhagic fever(CCHF)is a hemorrhagic fever caused by infection with the CCHF virus(CCHFV)and has a mortality rate of up to 30%.Thrombocytopenia is a hallmark of CCHF;however,the mechanisms underlying this manifestation remain poorly understood.In addition to hemostasis,platelets play a crucial role in recognizing pathogens and mediating immune responses.We investigated the mechanisms underlying thrombocytopenia associated with CCHFV infection by analyzing the platelet transcriptome in mice.Interferon-induced transmembrane protein 3(IFITM3),a known antiviral factor,was significantly upregulated.The role of IFITM3 in response to CCHFV infection was characterized using the human megakaryoblast cell line MEG-01,considered a parental cell line of platelets.Although the CCHFV infection rate was limited,MEG-01 cells maintained the infection and replication of CCHFV,leading to increased IFITM3 protein expression.We demonstrated that IFITM3 overexpression efficiently inhibited CCHFV infection,whereas IFITM3 knockout promoted viral infection.An interaction between IFITM3 and the CCHFV glycoprotein Gc was identified,which suppressed CCHFV entry into cells.The IFITM3 CIL-TMD domain is critical for this interaction.These results suggest that IFITM3 is a restriction factor and plays an antiviral role during CCHFV infection.Elevated expression of IFITM3 in platelets indicates that this could be a common mechanism by which platelets protect against viruses,including CCHFV,which may reduce platelet consumption and destruction caused by CCHFV infection.These findings provide valuable insights into the pathogenesis of CCHF-associated thrombocytopenia and offer foundational theoretical support for future therapeutic strategies.展开更多
Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus(SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective stu...Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus(SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective studies of epidemic outbreaks. Here, we report three confirmed patients(2015–2016) with typical symptoms of severe fever with thrombocytopenia syndrome disease(SFTS) who were farmers resident in different regions in Hubei Province. Three new SFTSV strains were isolated from the serum samples of each patient. Characterization of viral growth properties showed that there were no significant differences in virus production. All strains were completely sequenced, and phylogenetic analysis showed that unlike the other strains from Hubei province, which belonged to the SFTSV C3 genotype, one of the three strains belonged to the SFTSV C2 genotype. These results suggested that multiple SFTSV genotypes have been circulating in Hubei Province, providing insights into SFTSV evolution and improving our understanding of SFTSV prevalence in Hubei Province.展开更多
Crimean-Congo hemorrhagic fever virus(CCHFV) is a highly pathogenic tick-borne virus with a fatality rate of up to 50% in humans. CCHFV is widely distributed in countries around the world.Outbreaks of CCHFV infection ...Crimean-Congo hemorrhagic fever virus(CCHFV) is a highly pathogenic tick-borne virus with a fatality rate of up to 50% in humans. CCHFV is widely distributed in countries around the world.Outbreaks of CCHFV infection in humans have occurred in prior years in Xinjiang Province, China.Epidemiological surveys have detected CCHFV RNA in ticks and animals; however, few isolates were identified. In this study, we identified and isolated a new CCHFV strain from Hyalomma asiaticum asiaticum ticks collected from north of Tarim Basin in Xinjiang, China. A preliminary investigation of infection and antigens expression of CCHFV was performed in newborn mice. The target tissues for CCHFV replication in newborn mice were identified. The analysis of the phylogenetic relationships with other Chinese strains suggested that diverse genotypes of CCHFV have circulated in Xinjiang for years. These findings provide important insights into our understanding of CCHFV infection and evolution as well as disease prevention and control for local residents.展开更多
Crimean-Congo hemorrhagic fever(CCHF)caused by the CCHF virus(CCHFV)is a tick-borne natural focal disease with a mortality rate of approximately 50%.CCHFV is widely prevalent in Africa,southern Asia,the Middle East,an...Crimean-Congo hemorrhagic fever(CCHF)caused by the CCHF virus(CCHFV)is a tick-borne natural focal disease with a mortality rate of approximately 50%.CCHFV is widely prevalent in Africa,southern Asia,the Middle East,and southeast Europe.CCHF outbreaks have been reported previously in Xinjiang province,China,especially in its southern region.Epidemiological surveys conducted on ticks and animals have revealed the presence of CCHFV strains in ticks,rodents,and infected individuals from cities and counties in southern Xinjiang.Phylogenetic analyses revealed that the Chinese CCHFV strains belong to one genotype,based on complete sequences of the S segments of its negative-stranded RNA genome.The present study reports two new CCHFV strains isolated from Hyalomma asiaticum asiaticum ticks collected from Fukang City and Wujiaqu City in the northern region of Xinjiang.Viral characteristics and their evolutionary relationships were analyzed through metagenomic and reverse-transcription PCR analyses;these analyses indicated that the genotype of both strains was different from that of other Chinese strains.Furthermore,previous reports of CCHFV in Xinjiang were reviewed and phylogenetic analyses were performed.CCHFV was found to prevail in Fukang City in Junggar Basin for more than 20 years,and that Fukang City and Wujiaqu City are considered natural reservoirs of different genotypes of CCHFV strains.Our findings facilitate the understanding of CCHFV distribution in Xinjiang province and provide insights into the evolutionary relationships among Chinese CCHFV strains.展开更多
The Crimean-Congo hemorrhagic fever virus(CCHFV),a member of the genus Orthonairovirus and family Nairoviridae,is transmitted by ticks and causes severe hemorrhagic disease in humans.To study the epidemiology of CCHFV...The Crimean-Congo hemorrhagic fever virus(CCHFV),a member of the genus Orthonairovirus and family Nairoviridae,is transmitted by ticks and causes severe hemorrhagic disease in humans.To study the epidemiology of CCHFV in different ecosystems in Xinjiang,China,a total of 58,932 ticks were collected from Tarim Basin,Junggar Basin,Tianshan Mountain,and Altai Mountain from 2014 to 2017.Hyalomma asiaticum asiaticum was the dominant tick species in Tarim and Junggar basins,whereas Dermacentor nuttalli and Hyalomma detritum were found in Tianshan Mountain and Altai Mountain,respectively.Reverse transcription-polymerase chain reaction of the CCHFV small(S)genome segment was used for the molecular detection.The CCHFV-positive percentage was 5.26%,6.85%,1.94%,and 5.56% in Tarim Basin,Junggar Basin,Tianshan Mountain,and Altai Mountain,respectively.Sequences of the S segment were used for phylogenetic analysis and the results showed that the newly identified CCHFV strains belonged to two clades.Our study confirms that H.asiaticum asiaticum is the major vector of CCHFV in desert habitats which is consistent with previous studies,and also suggests that H.detritum and D.nuttalli are emerging vectors for CCHFV in Xinjiang.Moreover,this study reports the presence of CCHFV in the mountain habitat of Xinjiang for the first time,suggesting that future surveillance of CCHFV should also include mountainous areas.展开更多
Emerging infectious diseases are major threats to human health.Most severe viral disease outbreaks occur in developing regions where health conditions are poor.With increased international travel and business,the poss...Emerging infectious diseases are major threats to human health.Most severe viral disease outbreaks occur in developing regions where health conditions are poor.With increased international travel and business,the possibility of eventually transmitting infectious viruses between different countries is increasing.The most effective approach in preventing viral diseases is vaccination.However,vaccines are not currently available for numerous viral diseases.Viruslike particles(VLPs) are engineered vaccine candidates that have been studied for decades.VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles.VLPs have antigenicity similar to that of the native virus,but are non-infectious as they lack key viral genetic material.VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines.Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses,which may offer effective antiviral protection.Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases.The infectious agents discussed include RNA viruses from different virus families,such as the Arenaviridae,Bunyaviridae,Caliciviridae,Coronaviridae,Filoviridae,Flaviviridae,Orthomyxoviridae,Paramyxoviridae,and Togaviridae families.展开更多
The Crimean-congo hemorrhagic fever virus(CCHFV)is a geographically widespread fatal pathogen. Identification of the epitope regions of the virus is important for the diagnosis and epidemiological studies of CCHFV inf...The Crimean-congo hemorrhagic fever virus(CCHFV)is a geographically widespread fatal pathogen. Identification of the epitope regions of the virus is important for the diagnosis and epidemiological studies of CCHFV infections.In this study,expression vectors carrying series truncated fragments of the NP(nucleocapsid protein)gene from the S fragment of CCHFV strain YL04057 were constructed.The recombinant proteins were expressed in E.coli and purified for detection.The antigenic of the truncated fragments of NP was detected with a polyclonal serum(rabbit)and 2 monoclonal(mAbs)(14B7 and 43E5)against CCHFV by Western-blot analyses. The results showed that the three expressed constructs,which all contained the region 235AA to 305AA could be detected by mAbs polyclonal serum.The results suggest that region 235-305 aa of NP is a highly antigenic region and is highly conserved in the NP protein.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),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
Recent outbreaks of Zika virus （ZIKV） infections in Oceania＇s islands and the Americas were characterized by high numbers of cases and the spread of the virus to new areas. To better understand the origin of ZIKV, ...Recent outbreaks of Zika virus （ZIKV） infections in Oceania＇s islands and the Americas were characterized by high numbers of cases and the spread of the virus to new areas. To better understand the origin of ZIKV, its epidemic history was reviewed. Although the available records and information are limited, two major genetic lineages of ZIKV were identified in previous studies. However, in this study, three lineages were identified based on a phylogenetic analysis of all virus sequences from GenBank, including those of the envelope protein （E） and non-structural protein 5 （NS5） coding regions. The spatial and temporal distributions of the three identified ZIKV lineages and the recombination events and mechanisms underlying their divergence and evolution were further elaborated. The potential migration pathway of ZIKV was also characterized. Our findings revealed the central roles of two African countries, Senegal and Cote d＇lvoire, in ZIKV evolution and genotypic divergence. Furthermore, our results suggested that the outbreaks in Asia and the Pacific islands originated from Africa. The results provide insights into the geographic origins of ZlKV outbreaks and the spread of the virus, and also contribute to a better understanding of ZlKV evolution, which is important for the prevention and control of ZlKV infections.展开更多
The newly emerged mosquito-borne Zika virus(ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including in...The newly emerged mosquito-borne Zika virus(ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles(VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies. In this study, we used a new strategy to produce ZIKV VLPs based on the baculovirus expression system and demonstrated the feasibility of their use as a vaccine candidate. The pre-membrane(prM) and envelope(E) proteins were co-expressed in insect cells and selfassembled into particles similar to ZIKV. We found that the ZIKV VLPs could be quickly and easily prepared in large quantities using this system. The VLPs were shown to have good immunogenicity in immunized mice, as they stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses. Thus, the baculovirus-based ZIKV VLP vaccine is a safe, effective and economical vaccine candidate for use against ZIKV.展开更多
基金supported by the National Key Research and Development Program of China(2022YFC2303300,2023YFC2605504)the National Natural Science Foundation of China(82172273 and 31670165)the Open Research Fund Program of the State Key Laboratory of Virology of China(2023JZZD-01).
文摘Dear Editor,Lassa virus(LASV)is the causative agent of the acute viral hemorrhagic Lassa fever(LF),which is classified into Mammarenavirus within the Arenaviridae family,with a single-stranded,negative-sense,bisegmented RNA genome.Due to its high pathogenicity and lethality,LASV is considered as a priority threat to public health,with an estimated cases of 300,000 infections and 5000 deaths annually.LASV was first isolated and described as a clinical entity in 1969 in Lassa,Nigeria(Garry,2023).LASV isolates of different geographic and host origins are highly diverse in genomic sequences and phylogenetically classified into up to seven lineages,with each lineage predominately localized in specific countries.Although the research on LF has been carried out for decades since the pathogen first characterized,there is no approved antiviral drugs or vaccines for clinical use against LASV to date(Grant et al.,2023).One possible reason that hindered the development of countermeasures is that the preclinical studies on authentic LASV are restricted in high bio-containment biosafety level 4(BSL-4)facilities.In this letter,we describe isolation,and characterization of the LASV from the clinical samples.And we applied a coadministration assay of antiviral drugs for LASV by using a clinically isolated Mammarenavirus lassaense strain in the BSL-4 facility,aiming to investigate new therapeutic strategies for LASV infection.
基金supported by the projects of National Virus Resource Center(NVRC-PY-03,E1YZ020501)Natural Science Foundation of Hubei Province(2022CFB564)+4 种基金Foundation of Hubei Provincial Health Commission(WJ2023M108)National Basic Science Data Sharing Platform(no.2018ZX10101004)National Basic Science Data Sharing Service Platform(no.NBSDC-DB-13)the International Cooperation Base of Hubei Province for Infection and Immunitysupported by Outstanding Medical Young Scholars of Hubei Province and Wuhan Young and Middle-aged Medical Backbone Talent Program.
文摘Acute respiratory tract infections(ARTIs)are among the leading causes of morbidity and mortality in children worldwide.Human adenovirus(HAdV)infections are estimated to account for at least 5%of pediatric ARTIs.The circulated genotypes of HAdV and the correlation between genotype and clinical manifestations in Wuhan,China,before and after the complete relaxation of nonpharmaceutical interventions against severe acute respiratory syndrome coronavirus 2,remain unknown.Here,101 HAdV strains were isolated from throat swab samples collected from hospitalized children with ARTIs who tested positive for HAdV nucleic acid.Of these,sixty-six strains from 2022 to twenty-three strains from 2023 were successfully genotyped and subjected to phylogenetic analysis based on the hexon,penton base,and fiber genes.Six genotypes,B3,C1,C2,C5,C104,and C108 were identified.HAdV-B3(84.85%)was the most prevalent type in 2022,while HAdV-C(86.96%),including C1,C2,C108,and C104,was the most prevalent in 2023.These strains were phylogenetically related to strains from Japan,China,and the United States in recent years.When comparing clinical characteristics,pediatric patients infected with B3,C1,C2,C5,C104,or C108 exhibited similar clinical manifestations,primarily fever and cough,but varying interleukin(IL)-10 levels.In conclusion,from June 2022 to September 2023,the circulated genotypes of HAdV in Wuhan included B3,C1,C2,C108,C5,and C104.The endemic pattern of HAdV in Wuhan,China,shifted from species B as the dominant type in 2022 to species C in 2023.
基金funded by the National Key Research and Development Program of China(grant number:2023YFC2306501)the Hubei Provincial Fund for Supporting High-Quality Development of the Seed Industry"Conservation and Utilization of Agricultural Germplasm Resources"Project(grant number:HBZY2023A001-16)。
文摘Encephalomyocarditis virus(EMCV),a potential zoonotic pathogen,poses significant socioeconomic and public health challenges across various host species.Although EMCV rarely triggers severe clinical symptoms in humans,its widespread prevalence and unique biological characteristics underscore the need for continuous surveillance and the development of effective therapeutics and prophylactics.In this study,we evaluated the neutralizing effects of a monoclonal antibody derived from the spleens of mice immunized with EMCV virus-like particles(VLPs),both in vitro and in vivo.Using recombinant DNA technology,we engineered a baculovirus system to express EMCVs P12A and 3C,facilitating the production of VLPs in Sf9 cells.These VLPs serve as antigens to immunize mice,leading to the isolation of the monoclonal antibody 45G3.This antibody exhibited high specificity for EMCV confor-mational epitopes,excluding linear epitopes,and demonstrated potent in vitro neutralizing activity,with an IC50 of 0.01873μg/mL.Immunoelectron microscopy(IEM)revealed a strong direct interaction between the 45G3 antibody and EMCV particles.Virus adsorption inhibition assays demonstrated that 45G3 effectively blocked viral attachment,thereby preventing further infection of host cells.These findings further support the notion of a robust interaction between the virus and the antibody.Moreover,in vivo assessments revealed that 45G3 significantly reduced viral loads in treated mice and improved survival outcomes following EMCV exposure.Additionally,posttreatment analysis revealed reduced tissue damage and a markedly decreased inflammatory response in the brain,indicating that the 45G3 antibody effectively blocked viral infection,thereby mitigating tissue damage and enhancing survival.These findings position 45G3 as a promising candidate for EMCV management and provide a strong foundation for the future development of antiviral drugs targeting this widespread virus.
基金supported by the National Natural Science Foundation of China(U20A2022 and 32372217)the National Key Research and Development Program of China(2022YFD2300700)the Free Exploration Program of State Key Laboratory of Crop Gene Exploration and Utilization in Sichuan Basin,China(SKL-ZY202216)。
文摘Adjustment of the sowing date is a widely used measure in rice production for adapting to high-temperature conditions.However,the impact of a delayed sowing date(DS)on rice quality may vary by variety and ecological conditions.In this study,we conducted experiments using four different sowing dates,the conventional sowing date 1(CS1),CS2(10 d later than CS1),DS1(30 d later than CS1),and DS2(30 d later than CS2),and three rice varieties,i.e.,Yixiangyou 2115,Fyou 498,and Chuanyou 6203.This experiment was conducted at four sites in the Sichuan Basin in 2018 and 2019 to evaluate the infuence of DS on the pasting properties of rice,which are a proxy for the eating and cooking quality(ECQ).In DS1 and DS2,the rice had a signifcantly greater amylose content(AC)but a lower protein content(PC),peak viscosity(PKV),cool paste viscosity(CPV),and hot paste viscosity(HPV)than in CS1 and CS2.Moreover,except for CS2 and DS1 in 2018,DS1 and DS2 led to 2.15-11.19%reductions in breakdown viscosity(BDV)and 23.46-108.47%increases in setback viscosity(SBV).However,the infuence of DS on rice pasting properties varied by study site and rice variety.In 2019,DS1 and DS2 led to BDV reductions of 2.35-9.33,2.61-8.61,10.03-17.78,and 2.06-8.93%,and SBV increases of 2.32-60.93,63.74-144.24,55.46-91.63,and-8.28-65.37%at the Dayi,Anzhou,Nanbu,and Shehong(except for SBV in CS2 and DS1)sites,respectively.DS resulted in greater reductions in PKV,HPV,CPV,and BDV and greater increases in the AC and SBV for Yixiangyou 2115 than for Chuanyou 6203 and Fyou 498.The correlation analysis indicated that PKV and HPV were signifcantly and positively related to the mean,maximum,and minimum temperatures after heading.These temperatures must be greater than 25.9,31.2,and 22.3℃,respectively,to increase the relative BDV and reduce the relative SBV of rice,thereby enhancing ECQ.In conclusion,DS might contribute to a signifcant deterioration in ECQ in machine-transplanted rice in the Sichuan Basin.A mean temperature above 25.9℃ after heading is required to improve the ECQ of rice.
基金supported by the the National Key R&D Program of China(2024YFC2310000)the Key Project of Key Laboratory of VirologyBiosafety in the Wuhan Institute of Virology,Chinese Academy of Sciences(2024JZZD-02),the Youth Project of the Wuhan Institute of Virology,Chinese Academy of Sciences(2023QNTJ-03)+2 种基金the"Open Competition for Selecting the Best Candidates"Project of the Wuhan East Lake New Technology Development Zone(2022KJB117)the Natural Science Foundation of Hubei Province(2024AFB986)the Medical Science Research Project of Wuhan Health Commission(WX23B09).
文摘Crimean-Congo hemorrhagic fever(CCHF)is a hemorrhagic fever caused by infection with the CCHF virus(CCHFV)and has a mortality rate of up to 30%.Thrombocytopenia is a hallmark of CCHF;however,the mechanisms underlying this manifestation remain poorly understood.In addition to hemostasis,platelets play a crucial role in recognizing pathogens and mediating immune responses.We investigated the mechanisms underlying thrombocytopenia associated with CCHFV infection by analyzing the platelet transcriptome in mice.Interferon-induced transmembrane protein 3(IFITM3),a known antiviral factor,was significantly upregulated.The role of IFITM3 in response to CCHFV infection was characterized using the human megakaryoblast cell line MEG-01,considered a parental cell line of platelets.Although the CCHFV infection rate was limited,MEG-01 cells maintained the infection and replication of CCHFV,leading to increased IFITM3 protein expression.We demonstrated that IFITM3 overexpression efficiently inhibited CCHFV infection,whereas IFITM3 knockout promoted viral infection.An interaction between IFITM3 and the CCHFV glycoprotein Gc was identified,which suppressed CCHFV entry into cells.The IFITM3 CIL-TMD domain is critical for this interaction.These results suggest that IFITM3 is a restriction factor and plays an antiviral role during CCHFV infection.Elevated expression of IFITM3 in platelets indicates that this could be a common mechanism by which platelets protect against viruses,including CCHFV,which may reduce platelet consumption and destruction caused by CCHFV infection.These findings provide valuable insights into the pathogenesis of CCHF-associated thrombocytopenia and offer foundational theoretical support for future therapeutic strategies.
基金supported by the Science and Technology Basic Work Program (2013FY113500)the National Key Research and Development Program (2016YFE 0113500) from the Ministry of Science and Technology of Chinathe European Union’s Horizon 2020 EVAg project (No 653316)
文摘Hubei Province is a major epidemic area of severe fever with thrombocytopenia syndrome bunyavirus(SFTSV) in China. However, to date, a few SFTSV strains have been isolated from Hubei Province, preventing effective studies of epidemic outbreaks. Here, we report three confirmed patients(2015–2016) with typical symptoms of severe fever with thrombocytopenia syndrome disease(SFTS) who were farmers resident in different regions in Hubei Province. Three new SFTSV strains were isolated from the serum samples of each patient. Characterization of viral growth properties showed that there were no significant differences in virus production. All strains were completely sequenced, and phylogenetic analysis showed that unlike the other strains from Hubei province, which belonged to the SFTSV C3 genotype, one of the three strains belonged to the SFTSV C2 genotype. These results suggested that multiple SFTSV genotypes have been circulating in Hubei Province, providing insights into SFTSV evolution and improving our understanding of SFTSV prevalence in Hubei Province.
基金supported by the Science and Technology Basic Work Program (2013FY113500) from the Ministry of Science and Technology of China
文摘Crimean-Congo hemorrhagic fever virus(CCHFV) is a highly pathogenic tick-borne virus with a fatality rate of up to 50% in humans. CCHFV is widely distributed in countries around the world.Outbreaks of CCHFV infection in humans have occurred in prior years in Xinjiang Province, China.Epidemiological surveys have detected CCHFV RNA in ticks and animals; however, few isolates were identified. In this study, we identified and isolated a new CCHFV strain from Hyalomma asiaticum asiaticum ticks collected from north of Tarim Basin in Xinjiang, China. A preliminary investigation of infection and antigens expression of CCHFV was performed in newborn mice. The target tissues for CCHFV replication in newborn mice were identified. The analysis of the phylogenetic relationships with other Chinese strains suggested that diverse genotypes of CCHFV have circulated in Xinjiang for years. These findings provide important insights into our understanding of CCHFV infection and evolution as well as disease prevention and control for local residents.
基金supported by the Science and Technology Basic Work Program (2013FY113500)the National Key Research and Development Program (2016YFE0113500) from the Ministry of Science and Technology of Chinathe European Union’s Horizon 2020 EVAg project (No 653316)
文摘Crimean-Congo hemorrhagic fever(CCHF)caused by the CCHF virus(CCHFV)is a tick-borne natural focal disease with a mortality rate of approximately 50%.CCHFV is widely prevalent in Africa,southern Asia,the Middle East,and southeast Europe.CCHF outbreaks have been reported previously in Xinjiang province,China,especially in its southern region.Epidemiological surveys conducted on ticks and animals have revealed the presence of CCHFV strains in ticks,rodents,and infected individuals from cities and counties in southern Xinjiang.Phylogenetic analyses revealed that the Chinese CCHFV strains belong to one genotype,based on complete sequences of the S segments of its negative-stranded RNA genome.The present study reports two new CCHFV strains isolated from Hyalomma asiaticum asiaticum ticks collected from Fukang City and Wujiaqu City in the northern region of Xinjiang.Viral characteristics and their evolutionary relationships were analyzed through metagenomic and reverse-transcription PCR analyses;these analyses indicated that the genotype of both strains was different from that of other Chinese strains.Furthermore,previous reports of CCHFV in Xinjiang were reviewed and phylogenetic analyses were performed.CCHFV was found to prevail in Fukang City in Junggar Basin for more than 20 years,and that Fukang City and Wujiaqu City are considered natural reservoirs of different genotypes of CCHFV strains.Our findings facilitate the understanding of CCHFV distribution in Xinjiang province and provide insights into the evolutionary relationships among Chinese CCHFV strains.
基金the Ministry of Science and Technology of China (2013FY113500)the grants from the National Science Foundation of China (Nos.81460303,81760365)the State Key Laboratory of Virology of China (No.2015IOV003)
文摘The Crimean-Congo hemorrhagic fever virus(CCHFV),a member of the genus Orthonairovirus and family Nairoviridae,is transmitted by ticks and causes severe hemorrhagic disease in humans.To study the epidemiology of CCHFV in different ecosystems in Xinjiang,China,a total of 58,932 ticks were collected from Tarim Basin,Junggar Basin,Tianshan Mountain,and Altai Mountain from 2014 to 2017.Hyalomma asiaticum asiaticum was the dominant tick species in Tarim and Junggar basins,whereas Dermacentor nuttalli and Hyalomma detritum were found in Tianshan Mountain and Altai Mountain,respectively.Reverse transcription-polymerase chain reaction of the CCHFV small(S)genome segment was used for the molecular detection.The CCHFV-positive percentage was 5.26%,6.85%,1.94%,and 5.56% in Tarim Basin,Junggar Basin,Tianshan Mountain,and Altai Mountain,respectively.Sequences of the S segment were used for phylogenetic analysis and the results showed that the newly identified CCHFV strains belonged to two clades.Our study confirms that H.asiaticum asiaticum is the major vector of CCHFV in desert habitats which is consistent with previous studies,and also suggests that H.detritum and D.nuttalli are emerging vectors for CCHFV in Xinjiang.Moreover,this study reports the presence of CCHFV in the mountain habitat of Xinjiang for the first time,suggesting that future surveillance of CCHFV should also include mountainous areas.
文摘Emerging infectious diseases are major threats to human health.Most severe viral disease outbreaks occur in developing regions where health conditions are poor.With increased international travel and business,the possibility of eventually transmitting infectious viruses between different countries is increasing.The most effective approach in preventing viral diseases is vaccination.However,vaccines are not currently available for numerous viral diseases.Viruslike particles(VLPs) are engineered vaccine candidates that have been studied for decades.VLPs are constructed by viral protein expression in various expression systems that promote the selfassembly of proteins into structures resembling virus particles.VLPs have antigenicity similar to that of the native virus,but are non-infectious as they lack key viral genetic material.VLP vaccines have attracted considerable research interest because they offer several advantages over traditional vaccines.Studies have shown that VLP vaccines can stimulate both humoral and cellular immune responses,which may offer effective antiviral protection.Here we review recent developments with VLP-based vaccines for several highly virulent emerging or re-emerging infectious diseases.The infectious agents discussed include RNA viruses from different virus families,such as the Arenaviridae,Bunyaviridae,Caliciviridae,Coronaviridae,Filoviridae,Flaviviridae,Orthomyxoviridae,Paramyxoviridae,and Togaviridae families.
基金National Key Technologies R&D Program of China during the 10th Five-Year Plan Period(2003BA712A08-03)The Knowledge Innovation Program of the Chinese Academy of Sciences(KSCX2-YW-N-065)+1 种基金The Foundation scientific and technological project from MOST(2007FY210700)The NSFC Grant(30860255)
文摘The Crimean-congo hemorrhagic fever virus(CCHFV)is a geographically widespread fatal pathogen. Identification of the epitope regions of the virus is important for the diagnosis and epidemiological studies of CCHFV infections.In this study,expression vectors carrying series truncated fragments of the NP(nucleocapsid protein)gene from the S fragment of CCHFV strain YL04057 were constructed.The recombinant proteins were expressed in E.coli and purified for detection.The antigenic of the truncated fragments of NP was detected with a polyclonal serum(rabbit)and 2 monoclonal(mAbs)(14B7 and 43E5)against CCHFV by Western-blot analyses. The results showed that the three expressed constructs,which all contained the region 235AA to 305AA could be detected by mAbs polyclonal serum.The results suggest that region 235-305 aa of NP is a highly antigenic region and is highly conserved in the NP protein.
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 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 Science and Technology Basic Work Program(2013FY113500)from the Ministry of Science and Technology of China
文摘Recent outbreaks of Zika virus （ZIKV） infections in Oceania＇s islands and the Americas were characterized by high numbers of cases and the spread of the virus to new areas. To better understand the origin of ZIKV, its epidemic history was reviewed. Although the available records and information are limited, two major genetic lineages of ZIKV were identified in previous studies. However, in this study, three lineages were identified based on a phylogenetic analysis of all virus sequences from GenBank, including those of the envelope protein （E） and non-structural protein 5 （NS5） coding regions. The spatial and temporal distributions of the three identified ZIKV lineages and the recombination events and mechanisms underlying their divergence and evolution were further elaborated. The potential migration pathway of ZIKV was also characterized. Our findings revealed the central roles of two African countries, Senegal and Cote d＇lvoire, in ZIKV evolution and genotypic divergence. Furthermore, our results suggested that the outbreaks in Asia and the Pacific islands originated from Africa. The results provide insights into the geographic origins of ZlKV outbreaks and the spread of the virus, and also contribute to a better understanding of ZlKV evolution, which is important for the prevention and control of ZlKV infections.
基金supported by the Science and Technology Basic Work Program (2013FY113500) from the Ministry of Science and Technology of Chinathe strategic priority research program of the Chinese Academy of Sciences (ZDRW-ZS2016-4)
文摘The newly emerged mosquito-borne Zika virus(ZIKV) strains pose a global challenge owing to its ability to cause microcephaly and neurological disorders. Several ZIKV vaccine candidates have been proposed, including inactivated and live attenuated virus vaccines, vector-based vaccines, DNA and RNA vaccines. These have been shown to be efficacious in preclinical studies in mice and nonhuman primates, but their use will potentially be a threat to immunocompromised individuals and pregnant women. Virus-like particles(VLPs) are empty particles composed merely of viral proteins, which can serve as a safe and valuable tool for clinical prevention and treatment strategies. In this study, we used a new strategy to produce ZIKV VLPs based on the baculovirus expression system and demonstrated the feasibility of their use as a vaccine candidate. The pre-membrane(prM) and envelope(E) proteins were co-expressed in insect cells and selfassembled into particles similar to ZIKV. We found that the ZIKV VLPs could be quickly and easily prepared in large quantities using this system. The VLPs were shown to have good immunogenicity in immunized mice, as they stimulated high levels of virus neutralizing antibody titers, ZIKV-specific IgG titers and potent memory T cell responses. Thus, the baculovirus-based ZIKV VLP vaccine is a safe, effective and economical vaccine candidate for use against ZIKV.
