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
为了从分子水平上初步探讨我国流行HAdV-4的基因特征以及分子进化规律,为HAdV-4在我国的疫情监测与防控以及疫苗研发提供科学数据,本研究通过对2013~2014年间在陕西、云南、吉林和山东4省发热呼吸道症候群监测病例鼻咽拭子标本中分离...为了从分子水平上初步探讨我国流行HAdV-4的基因特征以及分子进化规律,为HAdV-4在我国的疫情监测与防控以及疫苗研发提供科学数据,本研究通过对2013~2014年间在陕西、云南、吉林和山东4省发热呼吸道症候群监测病例鼻咽拭子标本中分离得到的HAdV-4毒株,分别进行Penton base,Hexon和Fiber三个靶基因的序列测定,同时下载GenBank数据库中所有我国及全球流行HAdV-4病毒株的上述三基因序列进行比对,构建基因亲缘性关系树,并使用生物信息学分析软件进行基因特征和分子进化分析。结果显示:全球HAdV-4病毒株可划分两个进化分支(HAdV-4p和HAdV-4a),我国自2008年至今流行的HAdV-4病毒株属于HAdV-4a进化分支,与全球优势流行株一致;HAdV-4p和HAdV-4a进化分支病毒株的三个基因序列在时间和空间上均具保守性和稳定性,核苷酸和氨基酸突变主要与不同进化分支密切相关;HAdV-4基于三个基因的估算进化速率分别为3.73×10-5碱基替代/位点/年,1.86×10-5碱基替代/位点/年和4.09×10-5碱基替代/位点/年;基于Fiber基因估算的最近共同祖先(The most recent common ancestor,tMRCA)结果显示,HAdV-4起源于1771年,其中HAdV-4p和HAdV-4a可分别追溯至1933年和1962年。为了进一步积累并完善上述HAdV病毒学监测数据,我国急需建立长期有效的HAdV监测体系。展开更多
During 2018–2019,a severe human adenovirus(HAdV)infection outbreak occurred in southern China.Here,we screened 18 respiratory pathogens in 1704 children(≤14 years old)hospitalized with acute respiratory illness in G...During 2018–2019,a severe human adenovirus(HAdV)infection outbreak occurred in southern China.Here,we screened 18 respiratory pathogens in 1704 children(≤14 years old)hospitalized with acute respiratory illness in Guangzhou,China,in 2019.In total,151 patients had positive HAdV test results;34.4%(52/151)of them exhibited severe illness.HAdV infection occurred throughout the year,with a peak in summer.The median patient age was 3.0(interquartile range:1.1–5.0)years.Patients with severe HAdV infection exhibited increases in12 clinical indexes(P≤0.019)and decreases in four indexes(P≤0.007),compared with patients exhibiting nonsevere infection.No significant differences were found in age or sex distribution according to HAdV infection severity(P>0.05);however,the distributions of comorbid disease and HAdV co-infection differed according to HAdV infection severity(P<0.05).The main epidemic types were HAdV-3(47.0%,71/151)and HAdV-7(46.4%,70/151).However,the severe illness rate was significantly higher in patients with HAdV-7(51.4%)than in patients with HAdV-3(19.7%)and other types of HAdV(20%)(P<0.001).Sequencing analysis of genomes/capsid genes of 13 HAdV-7 isolates revealed high similarity to previous Chinese isolates.A representative HAdV-7isolate exhibited a similar proliferation curve to the curve described for the epidemic HAdV-3 strain Guangzhou01(accession no.DQ099432)(P>0.05);the HAdV-7 isolate exhibited stronger virulence and infectivity,compared with HAdV-3(P<0.001).Overall,comorbid disease,HAdV co-infection,and high virulence and infectivity of HAdV-7 were critical risk factors for severe HAdV infection;these data can facilitate treatment,control,and prevention of HAdV infection.展开更多
Human adenoviruses type 26(HAdV26)and type 35(HAdV35)have increasingly become the choice of adenovirus vectors for vaccine application.However,the population pre-existing immunity to these two adenoviruses in China,wh...Human adenoviruses type 26(HAdV26)and type 35(HAdV35)have increasingly become the choice of adenovirus vectors for vaccine application.However,the population pre-existing immunity to these two adenoviruses in China,which may reduce vaccine efficacy,remains largely unknown.Here,we established micro-neutralizing(MN)assays to investigate the seroprevalence of neutralizing antibodies(nAbs)against HAdV26 and HAdV35 in the general population of Guangdong and Shandong provinces,China.A total of 1184 serum samples were collected,47.0%and 15.8%of which showed HAdV26 and HAdV35 nAb activity,respectively.HAdV26-seropositive individuals tended to have more moderate nAbs titers(201-1000),while HAdV35-seropositive individuals appeared to have more low nAbs titers(72-200).The seropositive rates of HAdV26 and HAdV35 in individuals younger than 20 years old were very low.The seropositive rates of HAdV26 increased with age before 70 years old and decreased thereafter,while HAdV35 seropositive rates did not show similar characteristics.Notably,the seropositive rates and nAb levels of both HAdV26 and HAdV35 were higher in Guangdong Province than in Shandong Province,but did not exert significant differences between males and females.The seroprevalence between HAdV26 and HAdV35 showed little correlation,and no significant cross-neutralizing activity was detected.These results clarified the characteristics of the herd immunity against HAdV26 and HAdV35,and provided information for the rational development and application of HAdV26 and HAdV35 as vaccine vectors in China.展开更多
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.
文摘为了从分子水平上初步探讨我国流行HAdV-4的基因特征以及分子进化规律,为HAdV-4在我国的疫情监测与防控以及疫苗研发提供科学数据,本研究通过对2013~2014年间在陕西、云南、吉林和山东4省发热呼吸道症候群监测病例鼻咽拭子标本中分离得到的HAdV-4毒株,分别进行Penton base,Hexon和Fiber三个靶基因的序列测定,同时下载GenBank数据库中所有我国及全球流行HAdV-4病毒株的上述三基因序列进行比对,构建基因亲缘性关系树,并使用生物信息学分析软件进行基因特征和分子进化分析。结果显示:全球HAdV-4病毒株可划分两个进化分支(HAdV-4p和HAdV-4a),我国自2008年至今流行的HAdV-4病毒株属于HAdV-4a进化分支,与全球优势流行株一致;HAdV-4p和HAdV-4a进化分支病毒株的三个基因序列在时间和空间上均具保守性和稳定性,核苷酸和氨基酸突变主要与不同进化分支密切相关;HAdV-4基于三个基因的估算进化速率分别为3.73×10-5碱基替代/位点/年,1.86×10-5碱基替代/位点/年和4.09×10-5碱基替代/位点/年;基于Fiber基因估算的最近共同祖先(The most recent common ancestor,tMRCA)结果显示,HAdV-4起源于1771年,其中HAdV-4p和HAdV-4a可分别追溯至1933年和1962年。为了进一步积累并完善上述HAdV病毒学监测数据,我国急需建立长期有效的HAdV监测体系。
基金supported by the Guangzhou Science and Technology Program-Zhongnanshan Medical Foundation of Guangdong Province(202102010359-ZNSA-2020003)the Emergency Key Program of Guangzhou Laboratory(EKPG21-13)+3 种基金the National Natural Science Foundation of China(81970003,31900877)the Natural Science Foundation of Guangdong Province of China(2018A030310401)Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease(GHMJLRID-Z-202109)the Special Project for COVID-19 Prevention and Control of Zhongnanshan Medical Foundation of Guangdong Province(ZNSA-2020012)。
文摘During 2018–2019,a severe human adenovirus(HAdV)infection outbreak occurred in southern China.Here,we screened 18 respiratory pathogens in 1704 children(≤14 years old)hospitalized with acute respiratory illness in Guangzhou,China,in 2019.In total,151 patients had positive HAdV test results;34.4%(52/151)of them exhibited severe illness.HAdV infection occurred throughout the year,with a peak in summer.The median patient age was 3.0(interquartile range:1.1–5.0)years.Patients with severe HAdV infection exhibited increases in12 clinical indexes(P≤0.019)and decreases in four indexes(P≤0.007),compared with patients exhibiting nonsevere infection.No significant differences were found in age or sex distribution according to HAdV infection severity(P>0.05);however,the distributions of comorbid disease and HAdV co-infection differed according to HAdV infection severity(P<0.05).The main epidemic types were HAdV-3(47.0%,71/151)and HAdV-7(46.4%,70/151).However,the severe illness rate was significantly higher in patients with HAdV-7(51.4%)than in patients with HAdV-3(19.7%)and other types of HAdV(20%)(P<0.001).Sequencing analysis of genomes/capsid genes of 13 HAdV-7 isolates revealed high similarity to previous Chinese isolates.A representative HAdV-7isolate exhibited a similar proliferation curve to the curve described for the epidemic HAdV-3 strain Guangzhou01(accession no.DQ099432)(P>0.05);the HAdV-7 isolate exhibited stronger virulence and infectivity,compared with HAdV-3(P<0.001).Overall,comorbid disease,HAdV co-infection,and high virulence and infectivity of HAdV-7 were critical risk factors for severe HAdV infection;these data can facilitate treatment,control,and prevention of HAdV infection.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29050701)the Emergency Key Program of Guangzhou (EKPG21-20)+2 种基金the China Evergrande Group funding for SARS-Co V-2 (2020GIRHHMS22)the Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2022009)the China Postdoctoral Science Foundation (2020M682942)
文摘Human adenoviruses type 26(HAdV26)and type 35(HAdV35)have increasingly become the choice of adenovirus vectors for vaccine application.However,the population pre-existing immunity to these two adenoviruses in China,which may reduce vaccine efficacy,remains largely unknown.Here,we established micro-neutralizing(MN)assays to investigate the seroprevalence of neutralizing antibodies(nAbs)against HAdV26 and HAdV35 in the general population of Guangdong and Shandong provinces,China.A total of 1184 serum samples were collected,47.0%and 15.8%of which showed HAdV26 and HAdV35 nAb activity,respectively.HAdV26-seropositive individuals tended to have more moderate nAbs titers(201-1000),while HAdV35-seropositive individuals appeared to have more low nAbs titers(72-200).The seropositive rates of HAdV26 and HAdV35 in individuals younger than 20 years old were very low.The seropositive rates of HAdV26 increased with age before 70 years old and decreased thereafter,while HAdV35 seropositive rates did not show similar characteristics.Notably,the seropositive rates and nAb levels of both HAdV26 and HAdV35 were higher in Guangdong Province than in Shandong Province,but did not exert significant differences between males and females.The seroprevalence between HAdV26 and HAdV35 showed little correlation,and no significant cross-neutralizing activity was detected.These results clarified the characteristics of the herd immunity against HAdV26 and HAdV35,and provided information for the rational development and application of HAdV26 and HAdV35 as vaccine vectors in China.