手足口病患儿外周血单核细胞亚群的研究

目的：探讨未经治疗和随访1、3、5 d手足口患儿外周血单核细胞亚群的变化。方法流式细胞仪检测104例未经治疗手足口患儿（包括阴性患儿62例,EV71阳性患儿37例,CVA16阳性患儿5例）和随访1、3、5 d的患儿外周血单核细胞CD14highCD16-亚群、CD14highCD16＋亚群和CD14lowCD16＋亚群。结果与健康儿童组相比,手足口患儿CD14highCD16＋单核细胞亚群所占总单核细胞比例明显升高（t =4.092,P ＜0.001）;CD14highCD16-亚群比例明显降低。阴性、EV71型、CVA16型患儿之间CD14highCD16-亚群、CD14highCD16＋亚群和CD14lowCD16＋亚群差异均无统计学意义。结论未经治疗的手足口患儿外周血单核细胞亚群的变化可能与EV71及CVA16病毒的持续感染有关,与病毒种类相关性不明显。     

Proteasome-dependent, ubiquitin-independent degradation of Daxx by the viral pp71 protein in human cytomegalovirus-infected cells

The cellular Daxx protein represses human cytomegalovirus (HCMV) gene expression from the major immediate early promoter. HCMV prevents Daxx-mediated silencing during lytic infection by delivering the viral pp71 tegument protein to the nucleus, where pp71 binds to and induces the proteasomal degradation of Daxx. In this study, we show that a functional ubiquitin pathway is not required for the proteasomal degradation of the endogenous Daxx protein by tegument-delivered pp71 in HCMV-infected cells, demonstrating that the pp71-mediated degradation of Daxx occurs through a proteasome-dependent, ubiquitin-independent pathway.     

Plasmid-mediated doxycycline resistance in a Yersinia pestis strain isolated from a rat

The emergence of antibiotic-resistant Yersinia pestis strains represents a public health concern. Two antibiotic-resistant Y. pestis strains isolated from Madagascar have been previously identified and characterised. Both strains carried conjugative plasmids that conferred resistance to streptomycin or to multiple antibacterial drugs, respectively. Here we characterised a novel Y. pestis strain (IP2180H) that exhibited resistance to doxycycline. This strain was isolated from a rat in Antananarivo (Madagascar) in 1998. Resistance was carried by a conjugative plasmid (pIP2180H) homologous to pB71 from Salmonella enterica. The plasmid of the previously identified streptomycin-resistant Y. pestis strain was also sequenced and it was found that the three antibiotic resistance Y. pestis plasmids sequenced until now are genetically unrelated and are also unrelated to multidrug resistance plasmids from the phylogenetically close bacterial species Yersinia pseudotuberculosis. The fact that the three antibiotic-resistant Malagasy Y. pestis strains were isolated from different hosts, at different times, from distant locations, and carried unrelated plasmids indicates independent horizontal acquisition of genetic material and further demonstrates the capacity of Y. pestis to acquire antibiotic resistance plasmids under natural conditions. Since these resistance plasmids can frequently carry or easily trap antibiotic resistance cassettes, the emergence of new multidrug-resistant Y. pestis strains may be expected and would represent a major health threat.     

2010-2015年防城港市手足口病病原学监测结果分析

目的 分析防城港市2010-2015年手足口病(hand, foot and mouth disease,HFMD)病原学特征,为制订针对性防控措施提供依据。 方法 收集该市2010-2015年HFMD病原学监测病例资料,采用描述性流行病学的方法进行分析。 结果 共检测1 405例,肠道病毒(enterovirus,EV)通用型核酸阳性率50.04%(703/1 504),其中,EV71、柯萨奇病毒A组16型(Coxackievirus A16,CoxA16)和其它EV(即未分型类)分别占22.19%(156/703)、19.20%(135/703)、58.61%(412/703)。2011年的主要病原体为EV71(62.90%, 39/62),其余5年均以其它EV为主,分别占2010年、2012年、2013年、2014年和2015年的70.73%(72/99)、 45.38%(54/119)、76.65%(151/197)、43.86%(75/171)和83.64 %(46/55)。优势毒株2月份为CoxA16、4月份为EV71,其余月份均为其它EV。监测病例和阳性病例男女性别比分别为1.67:1和2.04:1;监测病例和阳性病例以≤4岁组为主,分别占87.47%(1 229/1 405)和90.19%(634/703)。病例广泛分布于各县(市、区)。由EV71阳性病例引起的重症发病率(16.03%, 25/156)明显高于其它EV(6.31%, 26/412)和CoxA16(0.74%, 1/135),三者差异有统计学意义(χ²=43.62,P<0.001)。肛拭子标本各种HFMD病原体检出率(54.52%)均明显高于咽拭子(24.40%),差异有统计学意义(χ²=64.53,P<0.001)。 结论 防城港市手足口病主要危害4岁以下儿童,其它EV为优势病原体,EV71阳性更容易导致重症病例发生。     

High Heterogeneity of Echoviruses in Brazilian Children with Acute Gastroenteritis

Echoviruses (E) are a diverse group of viruses responsible for various pathological conditions in humans including aseptic meningitis, myocarditis, and acute flaccid paralysis. The detection and identification of echovirus genotypes in clinical samples is challenging due to its high genetic diversity. Here, we report the complete genome sequences of nine echoviruses, obtained by next-generation sequencing of 238 fecal samples from individuals with gastroenteritis in regions of Brazil. Detected viruses were classified into six genotypes: Three E1 sequences (BRA/TO-028, BRA/TO-069 and BRA/TO-236), one E3 (BRA/TO-018), one E11 (BRA/TO-086), one E20 (BRA/TO-016), two E29 (BRA/TO-030 and BRA/TO-193), and one E30 sequence (BRA/TO-032). Phylogenetic analysis indicated that the echoviruses E1 and E29 circulating in Brazil are divergent from strains circulating worldwide. The genotype diversity identified in our study may under-represent the total echovirus diversity in Brazil because of the small sample size and the restricted geographical distribution covered by the survey.     

Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.     

Circulation and Molecular Epidemiology of Enteroviruses in Paralyzed,Immunodeficient and Healthy Individuals in Tunisia,a Country with a Polio-Free Status for Decades

This report is an overview of enterovirus (EV) detection in Tunisian polio-suspected paralytic cases (acute flaccid paralysis (AFP) cases), healthy contacts and patients with primary immunodeficiencies (PID) during an 11-year period. A total of 2735 clinical samples were analyzed for EV isolation and type identification, according to the recommended protocols of the World Health Organization. Three poliovirus (PV) serotypes and 28 different nonpolio enteroviruses (NPEVs) were detected. The NPEV detection rate was 4.3%, 2.8% and 12.4% in AFP cases, healthy contacts and PID patients, respectively. The predominant species was EV-B, and the circulation of viruses from species EV-A was noted since 2011. All PVs detected were of Sabin origin. The PV detection rate was higher in PID patients compared to AFP cases and contacts (6.8%, 1.5% and 1.3% respectively). PV2 was not detected since 2015. Using nucleotide sequencing of the entire VP1 region, 61 strains were characterized as Sabin-like. Among them, six strains of types 1 and 3 PV were identified as pre-vaccine-derived polioviruses (VDPVs). Five type 2 PV, four strains belonging to type 1 PV and two strains belonging to type 3 PV, were classified as iVDPVs. The data presented provide a comprehensive picture of EVs circulating in Tunisia over an 11-year period, reveal changes in their epidemiology as compared to previous studies and highlight the need to set up a warning system to avoid unnoticed PVs.     

山东省首例手足口病死亡病例调查与确认报告

手足口病是5岁以下幼儿的常见病,一般预后较好,但如果救治不及时易发展为重症,甚至死亡。2014年7月1日,菏泽市报告了一例手足口病死亡病例,该病例亦为山东省首例死亡病例。为了确认该病例的感染病原体和死亡原因,通过流行病学调查方法、询问患者家属及医务人员、查阅病例等方法了解到该病例先后在两家村级卫生室就诊,后转到市传染病医院,虽经极力抢救,仍因手足口病合并病毒性脑炎和神经源性肺水肿,呼吸、循环衰竭而死。经肛拭子标本实时定量PCR检测,该病例检测结果为EV71感染。应进一步加强手足口病的防控措施,重点关注对农村地区的病例指导时就医,降低手足口病的重症率和死亡率。