The frequent emergence of coronavirus(CoV)epidemics has seriously threatened public health and stock farming.The major hosts for CoVs are birds and mammals.Although most CoVs inhabit their specific natural hosts,some ...The frequent emergence of coronavirus(CoV)epidemics has seriously threatened public health and stock farming.The major hosts for CoVs are birds and mammals.Although most CoVs inhabit their specific natural hosts,some may occasionally cross the host barrier to infect livestock and even people,causing a variety of diseases.Since the beginning of the new century,increasing attention has been given to research on CoVs due to the emergence of highly pathogenic and genetically diverse CoVs that have caused several epidemics,including the recent COVID-19 pandemic.CoVs belong to the Coronaviridae family of the Nidovirales order.Recently,advanced techniques for viral detection and viral genome analyses have enabled characterization of many new nidoviruses than ever and have greatly expanded the Nidovirales order with new classification and nomenclature.Here,we first provide an overview of the latest research progress in the classification of the Nidovirales order and then introduce the host range,genetic variation,genomic pattern and pathogenic features of epidemic CoVs and other epidemic viruses.This information will promote understanding of the phylogenetic relationship and infectious transmission of various pathogenic nidoviruses,including epidemic CoVs,which will benefit virological research and viral disease control.展开更多
Background:C hina is a high-burden country for multidrug-r esistant tuberculosis/rifampin-resistant tuberculosis(MDR/RR-T B).Fluoroquinolones(FQs)are key drugs for the treatment of patients with MDR/RR-T B.However,res...Background:C hina is a high-burden country for multidrug-r esistant tuberculosis/rifampin-resistant tuberculosis(MDR/RR-T B).Fluoroquinolones(FQs)are key drugs for the treatment of patients with MDR/RR-T B.However,research on the resistance of FQs in Beijing is limited.Methods:W e collected clinical isolates from all patients with pulmonary TB in Beijing from January 2016 to December 2021,conducted drug-s ensitivity tests and sequencing for levofloxacin(LFX)and moxifloxacin(MFX),and collected the treatment plans and outcomes of the patients.Results:A total of 8512 clinical isolates were collected from patients with pulmonary TB,and 261 RR-T B strains were screened.The proportions of drug-s ensitive and drugresistant strains significantly differed by age group and treatment history.The rates of LFX and MFX resistance were 27.6%(72/261)and 36.4%(95/261),respectively.The detection rates of MDR-T B and pre-e xtensively drug-resistant TB(pre-X DR-T B)were 73.2%(191/261)and 36.4%(95/261),respectively,and the trends were significant(χ^(2)trend=9.995,p=0.002;χ^(2)trend=12.744,p=0.026).Among the 261 RR-T B strains,14.9%(24/261)were sensitive to LFX but resistant to MFX.Among the four patients with LFX-r esistant TB who received LFX treatment failed in three patients(Fisher's exact test,p=0.009).The common mutation sites were 94 and 90 in gyrA.A novel mutation Ala90Ser was discovered.Conclusions:F Qs resistance trends in RR-T B patients in Beijing are striking.Strains showed incomplete cross-resistance to LFX and MFX.Testing for FQs resistance and developing a reasonable treatment plan are recommended.Attention should be given to the changing trends in MDR-T B and pre-X DR-TB.展开更多
Objective This study aimed to explore the association between body mass index(BMI)and mortality based on the 10-year population-based multicenter prospective study.Methods A general population-based multicenter prospe...Objective This study aimed to explore the association between body mass index(BMI)and mortality based on the 10-year population-based multicenter prospective study.Methods A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023.Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality.Stratified analyses were performed based on the individual characteristics of the participants.Results Overall,19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died.The underweight(<18.5 kg/m^(2))presented an increase in all-cause mortality(adjusted hazards ratio[aHR]=2.00,95%confidence interval[CI]:1.66–2.41),while overweight(≥24.0 to<28.0 kg/m^(2))and obesity(≥28.0 kg/m^(2))presented a decrease with an aHR of 0.61(95%CI:0.52–0.73)and 0.51(95%CI:0.37–0.70),respectively.Overweight(aHR=0.76,95%CI:0.67–0.86)and mild obesity(aHR=0.72,95%CI:0.59–0.87)had a positive impact on mortality in people older than 60 years.All-2 cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m(aHR=0.95,95%CI:0.92–0.98)and increased slightly above that value,indicating a U-shaped association.The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.Conclusion This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years.Therefore,it is essential to consider age differences when formulating health and weight management strategies.展开更多
Dear Editor,Influenza viruses cause significant mortality and morbidity in humans.Vaccination is currently the most effective way to combat the virus(Perofsky and Nelson,2020).Unfortunately,the influenza virus frequen...Dear Editor,Influenza viruses cause significant mortality and morbidity in humans.Vaccination is currently the most effective way to combat the virus(Perofsky and Nelson,2020).Unfortunately,the influenza virus frequently changes its antigenicity through rapid mutations,leading to decreased vaccine efficacy or even failure.To improve vaccine effectiveness,it is necessary to monitor antigenic variation and update vaccine strains when significant antigenic variation occurs(Perofsky and Nelson,2020;Malik et al.,2024).展开更多
During the final proofing stage of the paper,the wrong version of Fig.2 was accidently used when replacing it with a high-resolution version.The star and circle marks were missing in the published version.
In 2022,cervical cancer accounted for approximately 662,301 new cases worldwide,representing 6.9%of all cancers diagnosed in women.Furthermore,it was the fourth leading cause of cancer-related deaths among women~1.In ...In 2022,cervical cancer accounted for approximately 662,301 new cases worldwide,representing 6.9%of all cancers diagnosed in women.Furthermore,it was the fourth leading cause of cancer-related deaths among women~1.In China,human papillomavirus(HPV)vaccination is not included in the National Immunization Program,thus creating marked urban±rural disparities:only 5.7%of rural children are vaccinated~2.Local publicly funded initiatives have increased vaccination uptake in some cities(e.g.,Shenzhen pilot;Jinan first-dose coverage>90%among eligible girls)~(3,4).展开更多
Human adenovirus type 108(HAdV-108)has been detected in multiple countries,including China,and is associated with severe acute respiratory infection(ARI)in children,with reported fatalities.However,studies on HAdV-108...Human adenovirus type 108(HAdV-108)has been detected in multiple countries,including China,and is associated with severe acute respiratory infection(ARI)in children,with reported fatalities.However,studies on HAdV-108 remain limited.This study aimed to investigate the clinical and genetic characteristics of HAdV-108 in ARI children in China.From 2014 to 2024,6720 respiratory samples were collected from hospitalized children with ARI at ten hospitals across northern and southern China,of which 505(7.51%)tested positive for HAdV.The whole-genome and three major capsid protein genes were amplified and sequenced for bioinformatics analysis,which revealed that among 317 HAdV-isolated samples,21(6.62%)were identified as HAdV-108,ranking third after HAdV-114 and HAdV-7.Clinical analysis of HAdV-108-positive cases showed that the main manifestations were cough and fever.Seven children had gastrointestinal symptoms,and two children without underlying diseases were diagnosed with severe pneumonia.Phylogenetic analysis of wholegenome sequences revealed distinct predominant epidemic branches between domestic and international strains,with one strain obtained in this study forming an independent branch.Hexon protein exhibited the fastest evolution rate,lowest identity,and greatest amino acid variability,while fiber protein displayed the slowest evolution rate,highest identity,and greatest conservation and stability.Compared with the earliest reported HAdV-108 strain,three amino acid deletions were identified in the RGD loop region of penton base protein,resulting in potential structural change.Recombination analysis identified five distinct recombination patterns.In vitro experiments demonstrated that HAdV-108 had proliferation capacity comparable to other species C adenoviruses.In summary,HAdV-108 has persistently circulated in China,causing severe ARIs and concurrent gastrointestinal manifestations.Cluster3 was the predominant epidemic branch in China.HAdV-108 exhibited significant intratype genetic variation,with random and diverse recombination events.展开更多
Infectious diseases are an enormous public health burden and a growing threat to human health worldwide.Emerging or classic recurrent pathogens,or pathogens with resistant traits,challenge our ability to diagnose and ...Infectious diseases are an enormous public health burden and a growing threat to human health worldwide.Emerging or classic recurrent pathogens,or pathogens with resistant traits,challenge our ability to diagnose and control infectious diseases.Nanopore sequencing technology has the potential to enhance our ability to diagnose,interrogate,and track infectious diseases due to the unrestricted read length and system portability.This review focuses on the application of nanopore sequencing technology in the clinical diagnosis of infectious diseases and includes the following:(i)a brief introduction to nanopore sequencing technology and Oxford Nanopore Technologies(ONT)sequencing platforms;(ii)strategies for nanopore-based sequencing technologies;and(iii)applications of nanopore sequencing technology in monitoring emerging pathogenic microorganisms,molecular detection of clinically relevant drug-resistance genes,and characterization of disease-related microbial communities.Finally,we discuss the current challenges,potential opportunities,and future outlook for applying nanopore sequencing technology in the diagnosis of infectious diseases.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a devastating pandemic worldwide.Vaccines and antiviral drugs are the most promising candidates for combating this global epidemic,and scientists a...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a devastating pandemic worldwide.Vaccines and antiviral drugs are the most promising candidates for combating this global epidemic,and scientists all over the world have made great efforts to this end.However,manipulation of the SARS-CoV-2 should be performed in the biosafety level3 laboratory.This makes experiments complicated and time-consuming.Therefore,a safer system for working with this virus is urgently needed.Here,we report the construction of plasmid-based,non-infectious SARS-CoV-2 replicons with turbo-green fluorescent protein and/or firefly luciferase reporters by reverse genetics using transformation-associated recombination cloning in Saccharomyces cerevisiae.Replication of these replicons was achieved simply by direct transfection of cells with the replicon plasmids as evident by the expression of reporter genes.Using SARS-CoV-2 replicons,the inhibitory effects of E64-D and remdesivir on SARS-CoV-2 replication were confirmed,and the halfmaximal effective concentration(EC50)value of remdesivir and E64-D was estimated by different quantification methods respectively,indicating that these SARS-CoV-2 replicons are useful tools for antiviral drug evaluation.展开更多
Dear Editor,In December 2019,a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19)in Wuhan,Hubei,China(Wu et al.2020;Zhu et al.2020).So far,this virus has spread to all ar...Dear Editor,In December 2019,a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19)in Wuhan,Hubei,China(Wu et al.2020;Zhu et al.2020).So far,this virus has spread to all areas of China and even to other countries.The epidemic has caused 67,102 confirmed infections with 1526 fatal cases worldwide by February 14th,2020.展开更多
Recently,a new type of unknown virus causing severe acute res-piratory infection was reported in Wuhan city,Hubei province,China(WHO,2020b).Infection of this virus was first reported in December 2019,and origin of the...Recently,a new type of unknown virus causing severe acute res-piratory infection was reported in Wuhan city,Hubei province,China(WHO,2020b).Infection of this virus was first reported in December 2019,and origin of the virus was traced back to a large seafood/wide animal market in Wuhan city.The serious clinical symptoms of the viral infection,including fever,dry cough,dys-pnea,and pneumonia,may result in progressive respiratory failure and even death.Moreover,the quick spread of the virus has caused an epidemic in China,as well as infection cases worldwide.The whole-genome sequence of Wuhan new virus(WH-Human_.1)was first released on January 10,2020(Zhang,2020),followed by additional ones released in Global Initiative on Sharing All Influ-enza Data(GISAID)(Shu and McCauley,2017).Later,this new virus was determined and announced as a new type of coronavirus(CoV;2019-nCoV)by the World Health Organization(WHO,2020a).展开更多
Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of internatio...Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.展开更多
A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene con...A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA,a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin.The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain(A/Alberta/01/2014).Further analysis showed that similar viruses have been circulating in wild birds in China,Russia,Dubai(Western Asia),Bulgaria and Romania(Europe),as well as domestic poultry in some regions of Africa.The affected areas include the Central Asian,East Asian-Australasian,West Asian-East African,and Black Sea/Mediterranean flyways.These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds,thus posing a serious threat to wild birds and potentially humans.展开更多
Dengue virus is an arthropod-borne pathogen that is transmitted to humans primarily by Aedes spp.mosquitos,causing the acute infectious disease,dengue fever(DF).Until 2019,no dengue outbreak had been reported in Haina...Dengue virus is an arthropod-borne pathogen that is transmitted to humans primarily by Aedes spp.mosquitos,causing the acute infectious disease,dengue fever(DF).Until 2019,no dengue outbreak had been reported in Hainan Province for over 20 years.However,in early September of 2019,an increasing number of infected cases appeared and the DF outbreak lasted for over one month in Haikou City,Hainan Province.In our study,we collected 97 plasma samples from DF patients at three hospitals,as well as 1585 mosquito larvae samples from puddles in different areas of Haikou.There were 49(50.5%)plasma samples found to be strongly positive and 9(9.3%)plasma samples were weakly positive against the NS1 antigen.We discovered DENV both in the patient's plasma samples and mosquito larvae samples,and isolated the virus from C6/36 cells inoculated with the acute phase serum of patients.Phylogenetic analysis revealed that the new strains were the most closely related to the epidemic strain in the southern regions of China,belonging to lineageⅣ,genotypeⅠ,DENV-1.Compared to the seven closest strains from neighboring countries and provinces,a total of 18 amino acid mutations occurred in the coding sequences(CDS)of the new isolated strain,DENV1 HMU-HKU-2.Our data shows that dengue virus is re-emerged in Hainan,and pose new threats for public health.Thus regular molecular epidemiological surveillance is necessary for control and prevention of DENV transmission.展开更多
Many paramyxoviruses are responsible for a variety of mild to severe human and animal diseases.Based on the novel discoveries over the past several decades,the family Paramyxoviridae infecting various hosts across the...Many paramyxoviruses are responsible for a variety of mild to severe human and animal diseases.Based on the novel discoveries over the past several decades,the family Paramyxoviridae infecting various hosts across the world includes 4 subfamilies,17 classified genera and 78 species now.However,no systematic surveys of bat paramyxoviruses are available from the Chinese mainland.In this study,13,064 samples from 54 bat species were collected and a comprehensive paramyxovirus survey was conducted.We obtained 94 new genome sequences distributed across paramyxoviruses from 22 bat species in seven provinces.Bayesian phylodynamic and phylogenetic analyses showed that there were four different lineages in the Jeilongvirus genus.Based on available data,results of host and region switches showed that the bat colony was partial to interior,whereas the rodent colony was exported,and the felines and hedgehogs were most likely the intermediate hosts from Scotophilus spp.rather than rodents.Based on the evolutionary trend,genus Jeilongvirus may have originated from Mus spp.in Australia,then transmitted to bats and rodents in Africa,Asia and Europe,and finally to bats and rodents in America.展开更多
Early etiological diagnosis is very important for the control of sudden viral infections,and requires antibodies with both high sensitivity and high specificity.Traditional antibody preparation methods have limitation...Early etiological diagnosis is very important for the control of sudden viral infections,and requires antibodies with both high sensitivity and high specificity.Traditional antibody preparation methods have limitations,such as a long and arduous cycle,complicated operation,and high expenses.A chicken lymphoma cell line,DT40,is known to produce IgM-type antibodies and undergo gene conversion and somatic mutation in the variable region of the immunoglobulin gene during culture.Here,the DT40 cell line was developed to produce antibody libraries and prepare antibody rapidly in vitro.Since hypermutation in DT40 cells was regulated by the activation-induced cytidine deaminase(AID)gene,AID expression needs to be controlled to either fix the Ig sequence by stopping mutation or improve affinity by resuming mutation after the antibodies have been selected.In this study,we generated a novel AID-inducible DT40 cell line(DT40-H7),in which the endogenous AID gene was knocked out using the CRISPR/Cas9 genome editing system,and an inducible AID gene,based on the Tet-Off expression system,was stably transfected.AID expression was controlled in DT40-H7 cells in a simple and efficient manner;gene conversion and point mutations were observed only when AID was expressed.Using the antibody library generated from this cell line,we successfully obtained monoclonal antibodies against the NS1 protein of Zika virus.The DT40-H7 cell line represents a useful tool for the selection and evolution of antibodies and may also be a powerful tool for the rapid selection and generation of diagnostic antibodies for emerging infectious diseases.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 risk of emerging infectious diseases(EID)is increasing globally.More than 60%of EIDs worldwide are caused by animal-borne pathogens.This study aimed to characterize the virome,analyze the phylogenetic evolution,an...The risk of emerging infectious diseases(EID)is increasing globally.More than 60%of EIDs worldwide are caused by animal-borne pathogens.This study aimed to characterize the virome,analyze the phylogenetic evolution,and determine the diversity of rodent-borne viruses in Hainan Province,China.We collected 682 anal and throat samples from rodents,combined them into 28 pools according to their species and location,and processed them for next-generation sequencing and bioinformatics analysis.The diverse viral contigs closely related to mammals were assigned to 22 viral families.Molecular clues of the important rodent-borne viruses were further identified by polymerase chain reaction for phylogenetic analysis and annotation of genetic characteristics such as arenavirus,coronavirus,astrovirus,pestivirus,parvovirus,and papillomavirus.We identified pestivirus and bocavirus in Leopoldoms edwardsi from Huangjinjiaoling,and bocavirus in Rattus andamanensis from the national nature reserves of Bangxi with low amino acid identity to known pathogens are proposed as the novel species,and their rodent hosts have not been previously reported to carry these viruses.These results expand our knowledge of viral classification and host range and suggest that there are highly diverse,undiscovered viruses that have evolved independently in their unique wildlife hosts in inaccessible areas.展开更多
Little is known about Subgenomic RNA(sgRNA)dynamics in patients with Coronavirus diseases 2019(COVID-19).We collected 147 throat swabs,74 gut swabs and 46 plasma samples from 117 COVID-19 patients recruited in the LOT...Little is known about Subgenomic RNA(sgRNA)dynamics in patients with Coronavirus diseases 2019(COVID-19).We collected 147 throat swabs,74 gut swabs and 46 plasma samples from 117 COVID-19 patients recruited in the LOTUS China trial(ChiCTR2000029308)and compared E and orf7a sgRNA load in patients with different illness duration,outcome,and comorbidities.Both sgRNAs were detected in all the three types of samples,with longest duration of 25,13,and 17 days for E sgRNA,and 32,28,and 17 days for orf7a sgRNA in throat,gut,and plasma,respectively.A total of 95%(57/60)of patients had no E sgRNA detected after 10 days post treatment,though 86%of them were still E RNA positive.High correlation on titer was observed between sgRNA encoding E and orf7a gene.sgRNA showed similar variation in the standard care and Lopinavir-Ritonavir group.Patients with diabetes and heart diseases showed higher pharyngeal E sgRNA at the first day(P=0.016 and 0.013,respectively)but no difference at five days after treatment,compared with patients without such commodities.Patients with hypertension and cerebrovascular diseases showed no difference in the pharyngeal sgRNA levels at both one and five days after treatment,compared with patients without these two commodities.E sgRNA levels in the initial infection showed no correlation with the serum antibody against spike,nucleoprotein,and receptor binding domains at ten days later.sgRNA lasted a long period in COVID-19 patients and might have little effect on humoral response.展开更多
Objective:To analyse the rar gene repertoire and characterise the rhondroitin sulphate A (CSA)-binding activity of the Duffy-binding like(I)BI.) domains encoded by the var2csa gene of a Plasmodium falciparum(P.falcipa...Objective:To analyse the rar gene repertoire and characterise the rhondroitin sulphate A (CSA)-binding activity of the Duffy-binding like(I)BI.) domains encoded by the var2csa gene of a Plasmodium falciparum(P.falciparum) isolate in Hainan Province,China.Methods:The sequences of var DBL1 regions were PCR-amplified,sequenced and the sequence characteristics was bioinformalically analysed.Recombinant proteins encoded by the var2csa genes were expressed and purified.The binding activities of the recombinant proteins to CSA receptor was detected by ELISA assays.Results:Fifty six unique DBI.a sequences were obtained,and the sequences represented similar diversity to the var genes of the genome parasite 3D7.There are two var2csa genes in the P.falciparum isolated from Hainan Province.Unlike in other falciparum parasites such as HB3,the two var2csa genes are more diverged.The receptor-binding capacity of DBL-5εand DBI.-6 e domains of HN var2CSA was studied.Conclusions:This work represented the diversity of rar genes of a P.falciparum isolate in China.展开更多
基金funded by the National Natural Science Foundation of China(No.32041001,81902070,U2002218)the Provincial Natural Science Foundation of Hunan Province(No.2019JJ20004 and 2019JJ50035).
文摘The frequent emergence of coronavirus(CoV)epidemics has seriously threatened public health and stock farming.The major hosts for CoVs are birds and mammals.Although most CoVs inhabit their specific natural hosts,some may occasionally cross the host barrier to infect livestock and even people,causing a variety of diseases.Since the beginning of the new century,increasing attention has been given to research on CoVs due to the emergence of highly pathogenic and genetically diverse CoVs that have caused several epidemics,including the recent COVID-19 pandemic.CoVs belong to the Coronaviridae family of the Nidovirales order.Recently,advanced techniques for viral detection and viral genome analyses have enabled characterization of many new nidoviruses than ever and have greatly expanded the Nidovirales order with new classification and nomenclature.Here,we first provide an overview of the latest research progress in the classification of the Nidovirales order and then introduce the host range,genetic variation,genomic pattern and pathogenic features of epidemic CoVs and other epidemic viruses.This information will promote understanding of the phylogenetic relationship and infectious transmission of various pathogenic nidoviruses,including epidemic CoVs,which will benefit virological research and viral disease control.
基金The Research and Cultivation Spectial Project of Beijing Center for Disease Prevention and Control,Grant/Award Number:2023-KYJH-03。
文摘Background:C hina is a high-burden country for multidrug-r esistant tuberculosis/rifampin-resistant tuberculosis(MDR/RR-T B).Fluoroquinolones(FQs)are key drugs for the treatment of patients with MDR/RR-T B.However,research on the resistance of FQs in Beijing is limited.Methods:W e collected clinical isolates from all patients with pulmonary TB in Beijing from January 2016 to December 2021,conducted drug-s ensitivity tests and sequencing for levofloxacin(LFX)and moxifloxacin(MFX),and collected the treatment plans and outcomes of the patients.Results:A total of 8512 clinical isolates were collected from patients with pulmonary TB,and 261 RR-T B strains were screened.The proportions of drug-s ensitive and drugresistant strains significantly differed by age group and treatment history.The rates of LFX and MFX resistance were 27.6%(72/261)and 36.4%(95/261),respectively.The detection rates of MDR-T B and pre-e xtensively drug-resistant TB(pre-X DR-T B)were 73.2%(191/261)and 36.4%(95/261),respectively,and the trends were significant(χ^(2)trend=9.995,p=0.002;χ^(2)trend=12.744,p=0.026).Among the 261 RR-T B strains,14.9%(24/261)were sensitive to LFX but resistant to MFX.Among the four patients with LFX-r esistant TB who received LFX treatment failed in three patients(Fisher's exact test,p=0.009).The common mutation sites were 94 and 90 in gyrA.A novel mutation Ala90Ser was discovered.Conclusions:F Qs resistance trends in RR-T B patients in Beijing are striking.Strains showed incomplete cross-resistance to LFX and MFX.Testing for FQs resistance and developing a reasonable treatment plan are recommended.Attention should be given to the changing trends in MDR-T B and pre-X DR-TB.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS)[grant number 2021-I2M-1-037]the National Natural Science Foundation of China[grant numbers 82373647,and 82473697].
文摘Objective This study aimed to explore the association between body mass index(BMI)and mortality based on the 10-year population-based multicenter prospective study.Methods A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023.Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality.Stratified analyses were performed based on the individual characteristics of the participants.Results Overall,19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died.The underweight(<18.5 kg/m^(2))presented an increase in all-cause mortality(adjusted hazards ratio[aHR]=2.00,95%confidence interval[CI]:1.66–2.41),while overweight(≥24.0 to<28.0 kg/m^(2))and obesity(≥28.0 kg/m^(2))presented a decrease with an aHR of 0.61(95%CI:0.52–0.73)and 0.51(95%CI:0.37–0.70),respectively.Overweight(aHR=0.76,95%CI:0.67–0.86)and mild obesity(aHR=0.72,95%CI:0.59–0.87)had a positive impact on mortality in people older than 60 years.All-2 cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m(aHR=0.95,95%CI:0.92–0.98)and increased slightly above that value,indicating a U-shaped association.The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.Conclusion This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years.Therefore,it is essential to consider age differences when formulating health and weight management strategies.
基金upported by the Major Project of Guangzhou National Laboratory(GZNL2024A01002)National Key Plan for Scientific Research and Development of China(2022YFC2303802)+1 种基金National Natural Science Foundation of China(32170651&32370700)Hunan Provincial Natural Science Foundation of China(2024JJ2015).
文摘Dear Editor,Influenza viruses cause significant mortality and morbidity in humans.Vaccination is currently the most effective way to combat the virus(Perofsky and Nelson,2020).Unfortunately,the influenza virus frequently changes its antigenicity through rapid mutations,leading to decreased vaccine efficacy or even failure.To improve vaccine effectiveness,it is necessary to monitor antigenic variation and update vaccine strains when significant antigenic variation occurs(Perofsky and Nelson,2020;Malik et al.,2024).
文摘During the final proofing stage of the paper,the wrong version of Fig.2 was accidently used when replacing it with a high-resolution version.The star and circle marks were missing in the published version.
基金supported by grants from the China Association for Science and Technology(KXYJS2024012)the Gates Foundation(INV-006373 and INV-023808)+1 种基金Capital’s Funds for Health Improvement and Research(2024-2-30117)Beijing Municipal Health Commission’s Funds for the Highqualified Public Health Professionals Development Project(Discipline Core-03-36)。
文摘In 2022,cervical cancer accounted for approximately 662,301 new cases worldwide,representing 6.9%of all cancers diagnosed in women.Furthermore,it was the fourth leading cause of cancer-related deaths among women~1.In China,human papillomavirus(HPV)vaccination is not included in the National Immunization Program,thus creating marked urban±rural disparities:only 5.7%of rural children are vaccinated~2.Local publicly funded initiatives have increased vaccination uptake in some cities(e.g.,Shenzhen pilot;Jinan first-dose coverage>90%among eligible girls)~(3,4).
基金supported by National Key Research and Development Program of China(2023YFC2306001)National Natural Science Foundation of China(No.32470141)+1 种基金the Beijing Research Center for Respiratory Infectious Diseases Project(BJRID2025-008)CAMS Innovation Fund for Medical Sciences(CIFMS,NO.2019-I2M-5–026,2022-I2M-CoV19-006).
文摘Human adenovirus type 108(HAdV-108)has been detected in multiple countries,including China,and is associated with severe acute respiratory infection(ARI)in children,with reported fatalities.However,studies on HAdV-108 remain limited.This study aimed to investigate the clinical and genetic characteristics of HAdV-108 in ARI children in China.From 2014 to 2024,6720 respiratory samples were collected from hospitalized children with ARI at ten hospitals across northern and southern China,of which 505(7.51%)tested positive for HAdV.The whole-genome and three major capsid protein genes were amplified and sequenced for bioinformatics analysis,which revealed that among 317 HAdV-isolated samples,21(6.62%)were identified as HAdV-108,ranking third after HAdV-114 and HAdV-7.Clinical analysis of HAdV-108-positive cases showed that the main manifestations were cough and fever.Seven children had gastrointestinal symptoms,and two children without underlying diseases were diagnosed with severe pneumonia.Phylogenetic analysis of wholegenome sequences revealed distinct predominant epidemic branches between domestic and international strains,with one strain obtained in this study forming an independent branch.Hexon protein exhibited the fastest evolution rate,lowest identity,and greatest amino acid variability,while fiber protein displayed the slowest evolution rate,highest identity,and greatest conservation and stability.Compared with the earliest reported HAdV-108 strain,three amino acid deletions were identified in the RGD loop region of penton base protein,resulting in potential structural change.Recombination analysis identified five distinct recombination patterns.In vitro experiments demonstrated that HAdV-108 had proliferation capacity comparable to other species C adenoviruses.In summary,HAdV-108 has persistently circulated in China,causing severe ARIs and concurrent gastrointestinal manifestations.Cluster3 was the predominant epidemic branch in China.HAdV-108 exhibited significant intratype genetic variation,with random and diverse recombination events.
基金supported by CAMS Innovation Fund for Medical Sciences (CIFMS)[2021-I2M-1-038]
文摘Infectious diseases are an enormous public health burden and a growing threat to human health worldwide.Emerging or classic recurrent pathogens,or pathogens with resistant traits,challenge our ability to diagnose and control infectious diseases.Nanopore sequencing technology has the potential to enhance our ability to diagnose,interrogate,and track infectious diseases due to the unrestricted read length and system portability.This review focuses on the application of nanopore sequencing technology in the clinical diagnosis of infectious diseases and includes the following:(i)a brief introduction to nanopore sequencing technology and Oxford Nanopore Technologies(ONT)sequencing platforms;(ii)strategies for nanopore-based sequencing technologies;and(iii)applications of nanopore sequencing technology in monitoring emerging pathogenic microorganisms,molecular detection of clinically relevant drug-resistance genes,and characterization of disease-related microbial communities.Finally,we discuss the current challenges,potential opportunities,and future outlook for applying nanopore sequencing technology in the diagnosis of infectious diseases.
基金supported by the CAMS Innovation Fund for Medical Science(CIFMS 2016-I2M-1-014)the National Key Plan for Scientific Research and Development of China(2016YFD0500300)+1 种基金National Key R&D Program of China(2020YFA0707600)Beijing Municipal Science and Technology Project(Z201100001020005)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a devastating pandemic worldwide.Vaccines and antiviral drugs are the most promising candidates for combating this global epidemic,and scientists all over the world have made great efforts to this end.However,manipulation of the SARS-CoV-2 should be performed in the biosafety level3 laboratory.This makes experiments complicated and time-consuming.Therefore,a safer system for working with this virus is urgently needed.Here,we report the construction of plasmid-based,non-infectious SARS-CoV-2 replicons with turbo-green fluorescent protein and/or firefly luciferase reporters by reverse genetics using transformation-associated recombination cloning in Saccharomyces cerevisiae.Replication of these replicons was achieved simply by direct transfection of cells with the replicon plasmids as evident by the expression of reporter genes.Using SARS-CoV-2 replicons,the inhibitory effects of E64-D and remdesivir on SARS-CoV-2 replication were confirmed,and the halfmaximal effective concentration(EC50)value of remdesivir and E64-D was estimated by different quantification methods respectively,indicating that these SARS-CoV-2 replicons are useful tools for antiviral drug evaluation.
基金jointly funded by the National Key Research and Development Program of China (Grant No. 2017YFD0500104)National Natural Science Foundation of China (Grant Nos. 31470260, 81902070)+2 种基金the Science Fund for Distinguished Young Scholars of Hunan Province (Grant No. 2019JJ20004)the Provincial Natural Science Foundation of Hunan Province (Grant Nos. 2019JJ50035, 2020SK3001)the Fundamental Research Funds for the Central Universities of China (Grant No. 531107051162)。
文摘Dear Editor,In December 2019,a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19)in Wuhan,Hubei,China(Wu et al.2020;Zhu et al.2020).So far,this virus has spread to all areas of China and even to other countries.The epidemic has caused 67,102 confirmed infections with 1526 fatal cases worldwide by February 14th,2020.
基金We would like to thank Dr.Yongzhen Zhang from Shanghai Public Health Clinical Center,Fudan University,Shanghai,China,and Dr.Zhengli Shi from the Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan,China,for providing the genome sequence of 2019-nCoV collected from Wuhan,China.This work is supported in part by grants from National Key R&D Program of China(2017YFC0908400,2017YFC1700200)National Natural Science Foundation of China(31900483).
文摘Recently,a new type of unknown virus causing severe acute res-piratory infection was reported in Wuhan city,Hubei province,China(WHO,2020b).Infection of this virus was first reported in December 2019,and origin of the virus was traced back to a large seafood/wide animal market in Wuhan city.The serious clinical symptoms of the viral infection,including fever,dry cough,dys-pnea,and pneumonia,may result in progressive respiratory failure and even death.Moreover,the quick spread of the virus has caused an epidemic in China,as well as infection cases worldwide.The whole-genome sequence of Wuhan new virus(WH-Human_.1)was first released on January 10,2020(Zhang,2020),followed by additional ones released in Global Initiative on Sharing All Influ-enza Data(GISAID)(Shu and McCauley,2017).Later,this new virus was determined and announced as a new type of coronavirus(CoV;2019-nCoV)by the World Health Organization(WHO,2020a).
基金This work was supported by the National Research and Development Project of China(Grant No.2020YFC0841100)Fundamental Research Funds for CAMS of China(Grant No.2020HY320001)+3 种基金National Key Research and Development Project of China(Grant No.2016YFD0500304)CAMS initiative for Innovative Medicine of China(Grant No.2016-I2M-2-006)National Mega projects of China for Major Infectious Diseases(Grant No.2017ZX10304402)and National Key Research and Development Programme of China(2016YFD0500301,2020YFC0840800,2020YFC0840900).
文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.
基金supported by grants from the National Natural Science Foundation of China (31311120063,81470096,31570026,31471253)the Ministry of Education and Science of the Russian Federation (Chinese-Russian project:RFMEFI61315X0045)+3 种基金the intramural special grant for influenza virus research from the Chinese Academy of Sciences (KJZD-EW-L09)the IDRCAPEIR program (106915-001)Special Project of Ministry of Science and Technology (2013FY113500)supported by the “Taishan Scholar” project of Shandong Province
文摘A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015.Based on the genetic and phylogenetic analyses,the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA,a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin.The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain(A/Alberta/01/2014).Further analysis showed that similar viruses have been circulating in wild birds in China,Russia,Dubai(Western Asia),Bulgaria and Romania(Europe),as well as domestic poultry in some regions of Africa.The affected areas include the Central Asian,East Asian-Australasian,West Asian-East African,and Black Sea/Mediterranean flyways.These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds,thus posing a serious threat to wild birds and potentially humans.
基金This work was supported by the Hainan Provincial Natural Science Foundation of China(Grant No.2019RC218)the National Natural Science Foundation of China(grant No.81860367,31460017)+5 种基金the Scientific Research Foundation of the Higher Education Institutions of Hainan Province,China(Grant No.Hnky2020-33)the Hainan Medical University novel coronavirus pneumonia project(Grant No.XGZX2020005)the Hainan Provincial Natural Science Foundation of China(Grant No.819QN360)State Key Laboratory of Virology 2018 Open Fund Project(2018IOV002)the National S&T Major Project"China Mega-Project for Infectious Disease"(Grant No.2018ZX10711001)the CAMS Innovation Fund for Medical Sciences(Grant No.2017-I2M-3-017).
文摘Dengue virus is an arthropod-borne pathogen that is transmitted to humans primarily by Aedes spp.mosquitos,causing the acute infectious disease,dengue fever(DF).Until 2019,no dengue outbreak had been reported in Hainan Province for over 20 years.However,in early September of 2019,an increasing number of infected cases appeared and the DF outbreak lasted for over one month in Haikou City,Hainan Province.In our study,we collected 97 plasma samples from DF patients at three hospitals,as well as 1585 mosquito larvae samples from puddles in different areas of Haikou.There were 49(50.5%)plasma samples found to be strongly positive and 9(9.3%)plasma samples were weakly positive against the NS1 antigen.We discovered DENV both in the patient's plasma samples and mosquito larvae samples,and isolated the virus from C6/36 cells inoculated with the acute phase serum of patients.Phylogenetic analysis revealed that the new strains were the most closely related to the epidemic strain in the southern regions of China,belonging to lineageⅣ,genotypeⅠ,DENV-1.Compared to the seven closest strains from neighboring countries and provinces,a total of 18 amino acid mutations occurred in the coding sequences(CDS)of the new isolated strain,DENV1 HMU-HKU-2.Our data shows that dengue virus is re-emerged in Hainan,and pose new threats for public health.Thus regular molecular epidemiological surveillance is necessary for control and prevention of DENV transmission.
基金supported by Beijing Natural Science Foundation(Grant No.M21002)the National Key R&D Program of China(Grant No.2021YFC2300902 and 2022YFE0210300)+3 种基金the CAMS Innovation Fund for Medical Sciences(Grant No.2021-I2M-1-038 and 2022-I2M-CoV19-002)Science&Technology Fundamental Resources Investigation Program(Grant No.2022FY100901)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310029)the Fundamental Research Funds for the Central Universities(Grant No.3332021092).
文摘Many paramyxoviruses are responsible for a variety of mild to severe human and animal diseases.Based on the novel discoveries over the past several decades,the family Paramyxoviridae infecting various hosts across the world includes 4 subfamilies,17 classified genera and 78 species now.However,no systematic surveys of bat paramyxoviruses are available from the Chinese mainland.In this study,13,064 samples from 54 bat species were collected and a comprehensive paramyxovirus survey was conducted.We obtained 94 new genome sequences distributed across paramyxoviruses from 22 bat species in seven provinces.Bayesian phylodynamic and phylogenetic analyses showed that there were four different lineages in the Jeilongvirus genus.Based on available data,results of host and region switches showed that the bat colony was partial to interior,whereas the rodent colony was exported,and the felines and hedgehogs were most likely the intermediate hosts from Scotophilus spp.rather than rodents.Based on the evolutionary trend,genus Jeilongvirus may have originated from Mus spp.in Australia,then transmitted to bats and rodents in Africa,Asia and Europe,and finally to bats and rodents in America.
基金sponsored by the Project of the National Defense Science and Technology Innovation Special Zone (to HH, 17-163-12-ZT-005-013-01)the CAMS Innovation Fund for Medical Sciences (to HH, CIFMS 2016-12 M-1-013 and to ZZ, CIFMS 2016-12 M-1-014 and 2016-12 M-3-020)+1 种基金the National Key Research and Development Program (to ZZ, 2016YFD0500300)the Fundamental Research Funds for the Central Universities (to HH, 2018PT31032)
文摘Early etiological diagnosis is very important for the control of sudden viral infections,and requires antibodies with both high sensitivity and high specificity.Traditional antibody preparation methods have limitations,such as a long and arduous cycle,complicated operation,and high expenses.A chicken lymphoma cell line,DT40,is known to produce IgM-type antibodies and undergo gene conversion and somatic mutation in the variable region of the immunoglobulin gene during culture.Here,the DT40 cell line was developed to produce antibody libraries and prepare antibody rapidly in vitro.Since hypermutation in DT40 cells was regulated by the activation-induced cytidine deaminase(AID)gene,AID expression needs to be controlled to either fix the Ig sequence by stopping mutation or improve affinity by resuming mutation after the antibodies have been selected.In this study,we generated a novel AID-inducible DT40 cell line(DT40-H7),in which the endogenous AID gene was knocked out using the CRISPR/Cas9 genome editing system,and an inducible AID gene,based on the Tet-Off expression system,was stably transfected.AID expression was controlled in DT40-H7 cells in a simple and efficient manner;gene conversion and point mutations were observed only when AID was expressed.Using the antibody library generated from this cell line,we successfully obtained monoclonal antibodies against the NS1 protein of Zika virus.The DT40-H7 cell line represents a useful tool for the selection and evolution of antibodies and may also be a powerful tool for the rapid selection and generation of diagnostic antibodies for emerging infectious diseases.
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This work was supported by Key Research and Development Plan of Hainan Province(No.ZDYF2020150,and ZDYF2022SHFZ085)the National Natural Science Foundation of China(Nos.32060015,81860367 and 82060378)+7 种基金CAMS Innovation Fund for Medical Sciences(CIFMS)(grant 2021-I2M-1-037,Grant No.2021-I2M-1-039)the Major Science and Technology Program of Hainan Province(No.ZDKJ202003)the Hainan Provincial Natural Science Foundation of China(Nos.820RC628 and 2019RC218)the National Key R&D Program of China(Grant No.2022YFE0210300)the Scientific Research Foundation of the Higher Education Institutions of Hainan Province,China(No.Hnky2021-40)the Research Project of the Hainan Academician Innovation Platform(No.YSPTZX202004)the Hainan Talent Development Project(No.SRC200003)Graduate student innovation grant of Hainan Medical University(No.HYYS2020-33,Hys2020-360,Hys2020-376 and Qhys2021-356)。
文摘The risk of emerging infectious diseases(EID)is increasing globally.More than 60%of EIDs worldwide are caused by animal-borne pathogens.This study aimed to characterize the virome,analyze the phylogenetic evolution,and determine the diversity of rodent-borne viruses in Hainan Province,China.We collected 682 anal and throat samples from rodents,combined them into 28 pools according to their species and location,and processed them for next-generation sequencing and bioinformatics analysis.The diverse viral contigs closely related to mammals were assigned to 22 viral families.Molecular clues of the important rodent-borne viruses were further identified by polymerase chain reaction for phylogenetic analysis and annotation of genetic characteristics such as arenavirus,coronavirus,astrovirus,pestivirus,parvovirus,and papillomavirus.We identified pestivirus and bocavirus in Leopoldoms edwardsi from Huangjinjiaoling,and bocavirus in Rattus andamanensis from the national nature reserves of Bangxi with low amino acid identity to known pathogens are proposed as the novel species,and their rodent hosts have not been previously reported to carry these viruses.These results expand our knowledge of viral classification and host range and suggest that there are highly diverse,undiscovered viruses that have evolved independently in their unique wildlife hosts in inaccessible areas.
基金supported by Natural Science Foundation of China(81900009 and 82041011/H0104)National Key Research and Development Program of China(2018YFC1200100 and 2018YFC1200102)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS 2018-I2M-1–003,2020-I2M-2–013,and 2020-I2M-CoV19-005)
文摘Little is known about Subgenomic RNA(sgRNA)dynamics in patients with Coronavirus diseases 2019(COVID-19).We collected 147 throat swabs,74 gut swabs and 46 plasma samples from 117 COVID-19 patients recruited in the LOTUS China trial(ChiCTR2000029308)and compared E and orf7a sgRNA load in patients with different illness duration,outcome,and comorbidities.Both sgRNAs were detected in all the three types of samples,with longest duration of 25,13,and 17 days for E sgRNA,and 32,28,and 17 days for orf7a sgRNA in throat,gut,and plasma,respectively.A total of 95%(57/60)of patients had no E sgRNA detected after 10 days post treatment,though 86%of them were still E RNA positive.High correlation on titer was observed between sgRNA encoding E and orf7a gene.sgRNA showed similar variation in the standard care and Lopinavir-Ritonavir group.Patients with diabetes and heart diseases showed higher pharyngeal E sgRNA at the first day(P=0.016 and 0.013,respectively)but no difference at five days after treatment,compared with patients without such commodities.Patients with hypertension and cerebrovascular diseases showed no difference in the pharyngeal sgRNA levels at both one and five days after treatment,compared with patients without these two commodities.E sgRNA levels in the initial infection showed no correlation with the serum antibody against spike,nucleoprotein,and receptor binding domains at ten days later.sgRNA lasted a long period in COVID-19 patients and might have little effect on humoral response.
基金supports to Q.Chen from the National Basic Research Program of China(973 Program,No.2007CB513100)national science and technology project(2008ZX-10004-011)NSFC grant to J.Yin (30771886),N.Jiang(81171592,)and Q.Chen(81130033)
文摘Objective:To analyse the rar gene repertoire and characterise the rhondroitin sulphate A (CSA)-binding activity of the Duffy-binding like(I)BI.) domains encoded by the var2csa gene of a Plasmodium falciparum(P.falciparum) isolate in Hainan Province,China.Methods:The sequences of var DBL1 regions were PCR-amplified,sequenced and the sequence characteristics was bioinformalically analysed.Recombinant proteins encoded by the var2csa genes were expressed and purified.The binding activities of the recombinant proteins to CSA receptor was detected by ELISA assays.Results:Fifty six unique DBI.a sequences were obtained,and the sequences represented similar diversity to the var genes of the genome parasite 3D7.There are two var2csa genes in the P.falciparum isolated from Hainan Province.Unlike in other falciparum parasites such as HB3,the two var2csa genes are more diverged.The receptor-binding capacity of DBL-5εand DBI.-6 e domains of HN var2CSA was studied.Conclusions:This work represented the diversity of rar genes of a P.falciparum isolate in China.
