Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

Human adenovirus(HAdV)infection in children with acute respiratory tract infections in Guangzhou,China,2010–2021:a molecular epidemiology study

Background Human adenovirus(HAdV)infection can cause a variety of diseases.It is a major pathogen of pediatric acute respiratory tract infections(ARIs)and can be life-threatening in younger children.We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou,China.Methods We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children’s Medical Center between 2010 and 2021.HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis.Results Before the COVID-19 outbreak in Guangzhou,the annual frequency of adenovirus infection detected during this period ranged from 3.92%to 13.58%,with an epidemic peak every four to fve years.HAdV demonstrated a clear seasonal distribution,with the lowest positivity in March and peaking during summer(July or August)every year.A signifcant increase in HAdV cases was recorded for 2018 and 2019,which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7.The latter was associated with a more severe disease compared to HAdV-3.The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38%but increased to 20%in severe cases.After COVID-19 emerged,HAdV cases dropped to 2.68%,suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community.Conclusion Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.

Hepatitis C virus infection in the human immunodeficiency virus infected patient

Human immunodeficiency virus(HIV)and hepatitis C virus(HCV)share the same transmission routes;therefore,coinfection is frequent.An estimated 5-10 million individuals alone in the western world are infected with both viruses.The majority of people acquire HCV by injection drug use and,to a lesser extent,through blood transfusion and blood products.Recently,there has been an increase in HCV infections among men who have sex with men.In the context of effective antiretroviral treatment,liver-related deaths are now more common than Acquired Immune Deficiency Syndromerelated deaths among HIV-HCV coinfected individuals.Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period for 15%-20%of chronically infected individuals.HCV treatment has rapidly changed with the development of new direct-acting antiviral agents;therefore,cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle.In this review,we focus on the epidemiology,diagnosis and the natural course of HCV as well as current and future strategies for HCV therapy in the context of HIV-HCV coinfection in the western world.

High frequencies of HGV and TTV infections in blood donors in Hangzhou

AIM: To determine the frequencies of HGV and TTV infections in blood donors in Hangzhou. METHODS: RT-nested PCR for HGV RNA detection and semi-nested PCR for TTV DNA detection in the sera from 203 blood donors, and nucleotide sequence analysis were performed. RESULTS: Thirty-two (15.8%) and 30 (14.8%) of the 203 serum samples were positive for HGV RNA and TTV DNA, respectively. And 5 (2.5%) of the 203 serum samples were detectable for both HGV RNA and TTV DNA. Homology of the nucleotide sequences of HGV RT-nested PCR products and TTV semi-nested PCR products from 3 serum samples compared with the reported HGV and TTV sequences was 89.36%, 87.94%, 88.65% and 63.51%, 65.77% and 67.12%, respectively. CONCLUSION: The infection rates of HGV and/or TTV in blood donors are relatively high, and to establish HGV and TTV examinations to screen blood donors is needed for transfusion security. The genomic heterogeneity of TTV or HGV is present in the isolates from different areas.

Aetiology of Tick-Borne Infections in an Adult Swedish Population—Are Co-Infections with Multiple Agents Common?

In Scandinavia, tick-borne infections affecting humans include Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA). Each of these infections can present with unspecific symptoms. In this prospective clinical study, we recruited patients based on two independent inclusion criteria;1) patients with unspecific symptoms, i.e. fever (≥38.0℃) or a history of feverishness and/or any combination of headache, myalgia or arthralgia and 2) patients with erythema migrans (EM), following an observed tick bite or tick exposure within one month prior to onset of symptoms. A total of 206 patients fulfilled the study. Among these, we could identify 186 cases of LB (174 with EM), 18 confirmed and two probable cases of HGA and two cases of TBE. Thirteen of the HGA cases presented without fever. Furthermore, 22 of the EM patients had a sub-clinical co-infection with Anaplasma phagocytophilum, based on serology. Both TBE cases had co-infections, one with Borrelia burgdorferi and one with Anaplasma phagocytophilum. We conclude that it is important to consider several causative agents and possible co-infections in the clinical management of infectious diseases where ticks may be suspected as vectors.

Women and Sexually Transmitted Infections in Africa

Despite efforts to control the spread of sexually transmitted infections (STIs), these infections are still highly prevalent in the developing world, especially in Africa where the prevalence and incidence of Human immunodeficiency virus (HIV) is also very high. Unfortunately, women bear the disproportionate burden of both STIs and HIV in this region. Early diagnosis, treatment and prevention of STIs is therefore crucial in this population given the strong evidence that some STIs have been shown to facilitate the transmission of HIV. This review summarizes the epidemiology, and management of the common STIs affecting African women, and the health complications associated with these infections in the era of emerging antimicrobial resistance.

Clinical characteristics and molecular epidemiology of human metapneumovirus in children with acute lower respiratory tract infections in China, 2017 to 2019: A multicentre prospective observational study

Human metapneumovirus(HMPV) infection is one of the leading causes of hospitalization in young children with acute respiratory illness. In this study, we prospectively collected respiratory tract samples from children who were hospitalized with acute lower respiratory tract infection in six hospitals in China from 2017 to 2019. HMPV was detected in 145 out of 2733 samples(5.3%) from the hospitalized children. The majority of HMPV-positive children were under the age of two(67.6%), with a median age of one year. HMPV can independently cause acute lower respiratory tract infection in young children, while all patients showed mild clinical symptoms. Of all the co-infected patients, HMPV was most commonly detected with enterovirus(EV) or rhinovirus(RhV)(38.0%),followed by respiratory syncytial virus(RSV)(32.0%). The highest detection rate occurred from March to May in both northern and southern China. Out of 145 HMPV positive samples, 48 were successfully typed, of which 36strains were subgrouped into subtypes A2c(75%), eight strains were included in subtype B1(16.7%), and four strains were included in subtype B2(8.3%). Moreover, 16 A2c strains contained 111-nucleotide duplications in the G gene. Twenty-seven complete HMPV genomes were successfully obtained, and 25(92.6%) strains belonged to subtype A2c, whereas one strain was included in subgroup B1 and another was included in subgroup B2. A total of 277 mutations were observed in the complete genomes of 25 A2c strains. All results presented here improve our understanding of clinical characteristics and molecular epidemiology of HMPV infection in children.

A multi-center study on Molecular Epidemiology of Human Respiratory Syncytial Virus from Children with Acute Lower Respiratory Tract Infections in the Mainland of China between 2015 and 2019

Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.

黄石地区住院儿童人偏肺病毒感染临床特征及流行病学分析

目的分析黄石地区住院儿童人偏肺病毒(HMPV)感染的流行病学特征及临床特点。方法回顾性分析2022年1月1日至12月31日黄石市中心医院收治的236例HMPV感染患儿的临床资料。按照病原菌感染类型和数量分为单纯HMPV感染组、混合病毒感染组和合并细菌感染组。比较各组患儿流行病学特征及临床特点。结果在236例HMPV感染患儿中,单纯HMPV感染143例(单纯HMPV感染组),占60.59%(143/236);合并其他病毒感染46例(混合病毒感染组),占19.49%;合并细菌感染47例(合并细菌感染组),占19.92%(47/236)。>1~3岁患儿HMPV感染数量最多,占55.51%(131/236)。合并细菌感染组喘息及肺炎患儿比例明显高于单纯HMPV感染组和混合病毒感染组(P<0.05)。合并细菌感染组天冬氨酸氨基转移酶、丙氨酸氨基转移酶水平及白细胞计数、淋巴细胞百分数、淋巴细胞计数、单核细胞计数均高于单纯HMPV感染组和混合病毒感染组(P<0.05)。HMPV感染构成比春季[61.44%(145/236)]显著高于冬季[25.00%(59/236)]、夏季[9.32%(22/236)]和秋季[4.24%(10/236)]。结论HMPV是引起儿童急性呼吸道感染的重要病原体之一,HMPV合并其他病原体感染可能增加儿童罹患肺炎的风险,>1~3岁患儿HMPV感染数量最多,春季是HMPV感染的高峰期。

宫颈HR-HPV持续性感染者中医体质及流行病学相关因素调查分析

目的探讨持续性宫颈高危型人乳头瘤病毒(HR-HPV)感染患者中医体质的特点及流行病学相关的危险因素。方法收集2021年11月至2022年10月于广州中医药大学深圳医院(福田)妇科进行宫颈癌筛查、符合纳排标准的72例持续性HR-HPV感染患者作为阳性组,另收集同一时段检查的HPV阴性且无其他基础疾病的105例健康女性作为阴性组,对其中医体质、流行病学相关因素进行问卷调查并进行统计学分析。结果平和质与持续性HR-HPV感染呈负相关,是保护性体质;职业为自由职业或家庭主妇、机关或专业技术人员及每日进食蔬菜水果与持续性HR-HPV感染呈负相关,较职业为体力劳动者或服务业、饮食上营养不均衡人群感染持续性HR-HPV的风险低;既往性伴侣个数、衣原体感染次数与持续性HR-HPV感染呈正相关,是持续性HR-HPV感染的危险因素。结论持续性HR-HPV感染与中医体质及流行病学相关因素具有相关性。

人腺病毒55型分子流行病学研究

近年来,人腺病毒55型(HAdV-55)在新兵、学生、医务人员中引起急性呼吸道感染的病例报道开始增多,HAdV-55已成为我国社区获得性肺炎的主要病原体之一,此型腺病毒应引起高度重视。本文对HAdV-55的一般特征、流行分布、疾病负担和基因进化进行综述,以期为人腺病毒55型疾病预防控制和疫苗研制提供参考依据。

Analysis of severe human adenovirus infection outbreak in Guangdong Province,southern China in 2019

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.

Current status of human adenovirus infection in China

Background Outbreaks of severe,acute hepatitis among children have recently attracted global attention.The pathogen causing the outbreak remains unknown,but there is growing evidence that it may be associated with human adenovirus(HAdV).Data sources A review of adenovirus-related clinical studies,epidemiological studies,etiological studies,and case reports was conducted by reviewers independently.Results HAdV can cause a wide variety of clinical symptoms.In the Mainland of China,HAdV infection accounts for 5.8%–13%of patients with acute respiratory infections,and these infections are mainly caused by species B,C,and E of HAdV.For acute conjunctivitis,39.8%–74.9%of sporadic cases were infected by B and D species of HAdV.Outbreaks of keratoconjunctivitis and pharyngoconjunctival fever related to HAdV infection could be found throughout the country.In pediatric patients with acute gastroenteritis,HAdV-41 was the predominant HAdV type,followed by HAdV species B and C.Several types of HAdV,including HAdV-5,HAdV-7,HAdV-1,and HAdV-2,have previously been reported as potential pathogens associated with HAdV hepatitis in immunocompromised patients.However,few HAdV-related hepatitis cases have been reported in China to date.Conclusions There are no systematic surveillance and clinical studies on HAdV hepatitis in China.Therefore,it is imperative to establish a nationwide HAdV virological surveillance system to collect relevant clinical,epidemiological and virological surveillance data and risk factor information as soon as possible to assess the potential risk of HAdV hepatitis among children.

Application of Human Adenovirus Genotyping by Phylogenetic Analysis in an Outbreak to Identify Nosocomial Infection

Nosocomial infections are common in pediatric patients and can be fatal in infants and immunocompromised patients. In September 2018, a high positive rate of human adenovirus HAdV was occurred among hospitalized children in the Children's Hospital Affiliated to the Capital Institute of Paediatrics in Beijing. To investigate whether this outbreak of HAdV was related to nosocomial infections or the result of community infections, we collected respiratory specimens from patients with acute respiratory infections in a respiratory ward during June to December 2018, and screened for respiratory viruses. Among 1,840 cases included, 95(5.2%, 95/1840) were positive for HAdV and 81 were genotyped based on phylogenetic analysis, including seven as HAdV-1(8.6%), 30 HAdV-3(37.0%), two HAdV-6(2.5%), and 42 HAdV-7(51.9%). More HAdV-positive samples were collected in August(4.7%, 12/255), September(15.0%, 41/274) and October(6.9%, 17/247), with a peak in September 2018. By combining the results of HAdV phylogenetic analysis with clinical data of patients, there were 77 cases(4.2%, 77/1840;81.1%, 77/95) excluded from nosocomial infections, eight cases representing possible infections transmitted by visitors or attending parents, three cases without sequences that might have been due to infection transmitted by roommates positive for HAdV, one case of a roommate without an HAdV sequence, and six cases that shared highly homologous sequences with those of their roommates, for which nosocomial infections might be considered. In conclusion, genotyping of HAdVs based on phylogenetic analysis combined with clinical information provides a powerful method to distinguish nosocomial infections from community acquired infection, especially when tracing the origins of nosocomial infections.

A six-year descriptive epidemiological study of human coronavirus infections in hospitalized patients in Hong Kong

We conducted a six-year epidemiological study on human coronaviruses（HCoVs） circulating in Hong Kong, using 8275 nasopharyngeal samples from patients with acute respiratory tract infections. HCoVs were detected in 77（0.93%） of the samples by a pan-HCoV RT-PCR assay. The most frequently detected HCoV species was HCoV-OC43（0.58%）, followed by HCoV-229E（0.15%）,HCoV-HKU1（0.13%） and HCoV-NL63（0.07%）. HCoVs were detected throughout the study period（September 2008–August 2014）, with the highest detection rate from September 2010 to August2011（22/1500, 1.47%）. Different seasonal patterns of each HCoV species in Hong Kong were noted.HCoV-OC43 was predominant in the fall and winter, whereas HCoV-HKU1 showed peak activity in winter, with a few cases occurred in spring and summer. HCoV-229 E mainly occurred in winter and spring, while HCoV-NL63 was predominant in summer and autumn. HCoVs most commonly infect the elderly and young children, with median age of 79.5 years（range, 22 days to 95 years）.Intriguingly, the detection rate of HCoV-OC43 in the age group of ＆gt; 80 years（26/2380, 1.09%） was significantly higher than that in the age group of 0–10 years（12/2529, 0.47%）（P 〈 0.05）. These data provides new insight into the epidemiology of coronaviruses.

河南省首例人感染H5N6禽流感病例的流行病学及临床特征

目的:分析河南省首例人感染H5N6禽流感病例的流行病学及临床特征。方法:2022年3月24日,河南省首次报告一例人感染H5N6禽流感确诊病例。参照《人感染动物源性流感预防控制技术指南(试行)》,疾控机构专业人员对病例开展现场流行病学调查,对涉及的工作场所、病例居住地以及禽类来源地等开展环境标本病原检测。结果:患者临床表现主要为高热、咳嗽、呼吸困难,后因呼吸衰竭死亡;病例有明确的禽肉相关暴露史,早期肺泡灌洗液、禽肉及工作场所环境标本H5N6禽流感病毒核酸均为阳性。结论:该例人感染H5N6禽流感病例通过职业暴露感染,未发现人传人的证据。

巨细胞病毒性肝炎研究进展

巨细胞病毒性肝炎是由人巨细胞病毒感染引起的,儿童和免疫功能低下肝病人群中最常见的一种肝脏疾病。该病无特异性表现,临床上易与其他病毒性肝炎混淆,导致失治误治。巨细胞病毒性肝炎的早期诊断至关重要,以便给予及时有效治疗,合理选择抗病毒药物及疗程。本文对巨细胞病毒性肝炎的病原学、流行病学、发病机制及临床表现、诊断治疗及预防的近年研究进展作一综述。

New light shed on global epidemiology of avian influenza A H5N1 virus infection in humans,1997—2015

With the support by the National Natural Science Foundation of China,the research team led by Prof.Yu Hongjie(余宏杰)at the School of Public Health,Fudan University,Key Laboratory of Public Health Safety,Ministry of Education,and the Key Laboratory of Surveillance and Early Warning on Infectious Disease,Chinese Center for Disease Control and Prevention,has published the paper entitled“Global epi-

2020~2021年呼和浩特市儿童呼吸道腺病毒感染的流行病学和实验室检测及临床特征研究

目的研究呼和浩特市儿童呼吸道腺病毒的流行病学特征、实验室指标、临床症状及病原体并发感染。方法选取2020年1月~2021年12月内蒙古自治区妇幼保健院就诊的急性呼吸道感染的住院患儿4266例,采用荧光定量PCR(real-time polymerase chain reaction,RT-PCR)法对患儿的咽拭子标本进行腺病毒核酸检测,结合一般信息,分析其流行病学及临床特征;将206例腺病毒核酸检测阳性患儿作为阳性组,另选取206例核酸阴性患儿作为对照组,阳性组按症状严重程度分为重症组(n=17)和非重症组(n=189),分别比较腺病毒阳性组和对照组、重症组与非重症组的临床特点、实验室生化指标和并发感染等。实验室生化指标包括白细胞(white blood cell,WBC)、中性粒细胞(neutrophil,NBC)、降钙素原(procacitonin,PCT)、C反应蛋白(C-reactive protein,CRP)和乳酸脱氢酶(lactate dehydrogenase,LDH)。结果4266例急性呼吸道感染的患儿,腺病毒总阳性率为4.83%(206/4266),男性(5.25%,131/2495)、女性(4.23%,75/1771)之间差异无统计学意义(χ^(2)=2.325,P>0.05)。夏季(8.14%,74/958)是感染高峰季节,6月~6岁的儿童容易感染腺病毒(87.86%,181/206),各年龄段阳性率差异有统计学意义(χ^(2)=28.332,P<0.05),其中6月~1岁感染率(6.72%,33/491)最高。阳性组CRP[5.78(0.93,16.18)mg/L]和NBC[4.82(2.82,8.20)×10^(9)/L]水平高于对照组[3.68(0.50,10.43)mg/L,3.91(2.01,6.61)×10^(9)/L],差异有统计学意义(Z=-2.373,-2.614,均P<0.05);重症组CRP[6.91(2.29,14.30)mg/L]和LDH[313.80(278.45,402.30)U/L]水平高于非重症组[1.70(0.50,11.95)mg/L,279.60(249.15,316.50)U/L],差异有统计学意义(Z=-2.027,-2.744,均P<0.05)。阳性组发热≥39℃(58.74%,121/206)、热程≥9天(14.08%,29/206)、腹泻(8.74%,18/206)和喘息(7.28%,15/206)发生率,与对照组[36.89%(76/206),6.80%(14/206),3.40%(7/206),14.08%(29/206)]相比差异有统计学意义(χ^(2)=19.698,5.842,5.153,4.987,均P<0.05),重症组喘息症状发生率(35.29%,6/17)高于非重症组(4.76%,9/189),差异有统计学意义(χ^(2)=17.251,P<0.05)。腺病毒阳性组与对照组相比,患儿易并发扁桃体炎、鼻窦炎和胃肠炎(χ^(2)=4.796,10.652,7.828,均P<0.05)。儿童腺病毒感染的临床症状以支气管肺炎(51.94%,107/206)最多见。腺病毒阳性组中,并发细菌感染率高于并发病毒和支原体感染(χ^(2)=24.793,23.298,均P<0.05)。结论呼和浩特市6月~6岁儿童容易感染腺病毒,引起以支气管肺炎为主的呼吸道疾病,常并发细菌感染,提示本地区应对儿童加强呼吸道腺病毒感染的防治。

55型人腺病毒致hDSG2转基因小鼠肺感染动物模型的建立及意义

背景55型人腺病毒(human adenovirus type 55,HAdV-B55)可引起呼吸道感染,严重者可发展为病毒性肺炎甚至危及生命。理想的HAdV-B55感染模型对发病机制、药物治疗以及多价疫苗的研制有重要价值。目的建立HAdV-B55人源化受体桥粒芯糖蛋白2(humanized receptor desmoglein-2,hDSG2)转基因小鼠肺感染动物模型。方法雄性hDSG2转基因小鼠、野生型C57BL/6(C57)小鼠各25只,按感染后3 d、5 d、7 d、14 d和PBS对照随机分为5组,每组5只,感染小鼠用HAdV-B55(108 TCID50)滴鼻进行感染,对照组用相同剂量的PBS滴鼻,每日称重并观察小鼠活动情况,分别于感染后3 d、5 d、7 d、14 d取材,对照组滴鼻后14 d取材。测定各组的肺系数、肺组织病理、肺组织内HAdV-B55基因拷贝量、白细胞介素-6(interleukin-6,IL-6)和γ干扰素表达水平以及血清中IL-6浓度水平。结果hDSG2转基因小鼠感染HAdV-B55病毒后一般状况较C57小鼠恢复慢,体质量增长较慢(P<0.01),且表现出活动减少、蜷缩抱团等急性感染症状;hDSG2转基因小鼠的肺组织病理表现较C57小鼠重,主要为肺泡壁增厚和炎性细胞浸润,同时肺系数增高显著(P<0.05),肺组织内HAdVB55基因拷贝量显著增多(P<0.05),肺组织内IL-6表达水平(P<0.05)与血清中IL-6浓度显著升高(P<0.01)。结论采用经鼻滴入HAdV-B55方法,可以建立hDSG2转基因小鼠肺感染的动物模型,该模型稳定性和持续致病性较好,具有进一步深入研究的价值。