Viral evolution and transmission effectiveness

Different viruses transmit among hosts with different degrees of efficiency. A basic reproductive number(R0) indicates an average number of cases getting infected from a single infected case. R0 can vary widely from a little over 1 to more than 10. Low R0 is usually found among rapidly evolving viruses that are often under a strong positive selection pressure, while high R0 is often found among viruses that are highly stable. The reason for the difference between antigenically diverse viruses with low R0, such as influenza A virus, and antigenically stable viruses with high R0, such as measles virus, is not clear and has been a subject of great interest. Optimization of transmissibility fitness considering intra-host dynamics and inter-host transmissibility was shown to result in strategies for tradeoff between transmissibility and diversity. The nature of transmission, targeting either a na?ve children population or an adult population with partial immunity, has been proposed as a contributing factor for the difference in the strategies used by the two groups of viruses. The R0 determines the levels of threshold heard immunity. Lower R0 requires lowerherd immunity to terminate an outbreak. Therefore, it can be assumed that the outbreak saturation can be reached more readily when the R0 is low. In addition, one may assume that when the outbreak saturation is reached, herd immunity may provide a strong positive selection pressure that could possibly result in an occurrence of escape mutants. Studies of these hypotheses will give us an important insight into viral evolution. This review discusses the above hypotheses as well as some possible mechanistic explanation for the difference in transmission efficiency of

Ecology, Distribution and Risk of Transmission of Viral Haemorrhagic Fevers by Aedes Mosquitoes around the Port Areas of Tema in Southern Ghana

Aedes-borne diseases remain a public health challenge for many countries globally. The extent of spread of invasive species of Aedes mosquitoes and risk of transmission of the diseases especially around the point of entry of goods such as ports is not well known in Ghana. This study investigated the ecology, distribution and risk of transmission of viral haemorrhagic fevers by Aedes mosquitoes around the port areas of Tema, Southern Ghana. The mosquitoes from this study were collected using human landing catches, ovitraps and larval collections for a period of six months. A total of 1092 containers were inspected in both seasons and of these, 237 (21.7%) were positive for mosquito larvae or pupae in rainy season while 181 (16.6%) were positive in dry season. A total of 6498 mosquitoes were collected and identified morphologically using taxonomic keys. 6038 (92.9%) were Aedes aegypti, 337 (5.2%) were Culex spp. and 123 (1.9%) were Anopheles gambiae. The Ae. aegypti larvae were found breeding in a series of water-holding containers which included disposed plastic containers, earthenware pots, car tyres, plastic barrels, plastic basins, buckets, metal drums, jerrycans and poly tank. A high proportion of Aedes aegypti eggs were found in the ovitraps during the rainy season than in the dry season in the study sites. Ae. aegypti was the most common mosquitoes biting mostly outdoors (65.6%) with more bites occurring in the rainy season (63.6%) in the two residential sites (Tema Community One and Tema New Town). The risk of transmission of viral haemorrhagic fever in the study sites was assessed using House Index, Container Index, Breteau Index and was found to be higher in Tema New town area with seasonal variations within the sites. The man-vector contact rates for the two residential sites were also found to be higher in rainy season than the dry season. These observations indicate that the risk of transmission of viral haemorrhagic fevers in the study areas is high especially in the rainy season. The implications of the findings in the formulation of future vector control programmes around the port areas in the country are discussed in the paper.

A prospective study of vertical transmission of hepatitis C virus

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Vertically acquired hepatitis C virus infection:Correlates oftransmission and disease progression

The worldwide prevalence of hepatitis C virus(HCV)infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, motherto-child transmission(MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance(SVC) that usually occurs within 6 years of life. IL-28 B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.

Epidemiology and transmission of hepatitis B and C viruses in Kazakhstan

AIM: To investigate the epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in the two major ethnic groups in Kazakhstan. METHODS: A cross-sectional prospective study of HBV and HCV seroprevalence was performed among individuals born in Kazakhstan with no history of chronic hepatitis or liver disease. RESULTS: There were 290 volunteers (140 Russians and 150 Kazakhs) aged 10 to 64 years, males accounted for 46%. Active HBV infection (HBsAg positive) was present in 3.8%, anti-HBc in 30%. The prevalence was similar in females and males (33% vs 25%) (P = 0.18). The prevalence of anti-HBc increased from 19% in 10-29 years old volunteers to 53% in 50-years and older volunteers. The prevalence of HBV infection was higher in married than in single adults (38% vs 26%, respectively) (P = 0.2) and more common in Kazakhs (35%) than in Russians (24%) (P = 0.07). HCV infection was present in 9 subjects (3.2%), 5 of them also were positive for anti-HBc in the absence of HBsAg. CONCLUSION: The frequency of active HBV infection (3.8%) coupled with a high prevalence of HBV exposure in those > 50 years of age increases with age, which suggests that horizontal transmission likely relates tothe use of contaminated needles. The low prevalence of HCV infection suggests that HBV and HCV are acquired differently in this group of subjects.

Leafhopper salivary carboxylesterase suppresses JA-Ile synthesis to facilitate initial arbovirus transmission in rice phloem

Plant jasmonoyl-L-isoleucine(JA-Ile)is a major defense signal against insect feeding,but whether or how insect salivary effectors suppress JA-Ile synthesis and thus facilitate viral transmission in the plant phloem remains elusive.Insect carboxylesterases(CarEs)are the third major family of detoxification enzymes.Here,we identify a new leafhopper CarE,CarE10,that is specifically expressed in salivary glands and is secreted into the rice phloem as a saliva component.Leafhopper CarE10 directly binds to rice jasmonate resistant 1(JAR1)and promotes its degradation by the proteasome system.Moreover,the direct association of CarE10 with JAR1 clearly impairs JAR1 enzyme activity for conversion of JA to JA-Ile in an in vitro JAIle synthesis system.A devastating rice reovirus activates and promotes the co-secretion of virions and CarE10 via virus-induced vesicles into the saliva-storing salivary cavities of the leafhopper vector and ultimately into the rice phloem to establish initial infection.Furthermore,a virus-mediated increase in CarE10 secretion or overexpression of CarE10 in transgenic rice plants causes reduced levels of JAR1 and thus suppresses JA-Ile synthesis,promoting host attractiveness to insect vectors and facilitating initial viral transmission.Our findings provide insight into how the insect salivary protein CarE10 suppresses host JA-Ile synthesis to promote initial virus transmission in the rice phloem.

Parents’s knowledge and awareness about hepatitis B can influence the vaccination of their children

BACKGROUND Birth-dose(Hep-BD)followed by three additional doses(Hep-B3)of hepatitis B virus(HBV)vaccine are key to eliminating HBV by 2030.Unfortunately,Hep-BD and Hep-B3 coverage in our country is poor.AIM To studied the parent’s knowledge and awareness about HBV infection,its prevention,consequences and vaccination.METHODS Parents of 6 months to 8 years old children were interviewed to assess their knowledge&awareness about hepatitis B,its transmission,prevention,illness caused by this,and vaccination.Eighteen close-ended questions were admini-stered,and responses were recorded as‘yes’,‘no’,or‘not sure’.HBV knowledge score was calculated based on the sum of correct answers.Each correct response scored one point and incorrect,missing or‘not sure’responses received no points.Categorical data are presented as number(%)and numerical data are expressed as median.Data were compared using Chi2 tests and level of significance was kept as P<0.05.RESULTS Parents(58.3%mothers)of 384 children(89.9%age<5 years;82%age-appropriately vaccinated)were included.Three hundred and twenty-two(83.9%)children were Hep-B3 vaccinated.94.3%,87.5%,and 29.2%parents knew about polio,tetanus,and hepatitis B vaccine.Overall,41.2%,15.8%,and 23%parents knew about hepatitis B transmission,consequences of infection,and prevention respectively.Only 7.6%parents knew about three-dose schedule of hepatitis B vaccination.Only 23%parents believed that vaccine could prevent HBV,15.7%knew that HBV affects liver.Parents of Hep-B3 vaccinated children were significantly more aware about HBV than the parents of unvaccinated children(P<0.05 for 17/18 questions).CONCLUSION The knowledge and awareness among the parents about hepatitis B is poor.The Increasing knowledge/awareness about HBV among parents may improve Hep-B3 vaccination coverage.

DEAD-box解旋酶21对猪传染性胃肠炎病毒复制的调控作用

旨在探究DEAD-box解旋酶21(DDX21)对猪传染性胃肠炎病毒(TGEV)复制的调控作用。首先通过蛋白免疫印迹(Western Blot)分析了TGEV感染对DDX21表达的影响;进一步构建了猪DDX21真核表达质粒以及建立稳定敲低DDX21的PK-15细胞系,运用荧光定量PCR(RT-qPCR)、蛋白免疫印迹、间接免疫荧光(IFA)和半数细胞培养物感染量(TCID 50)探究外源过表达DDX21及敲低DDX21对TGEV体外复制的调控作用;构建一系列DDX21截短突变体真核表达质粒,鉴定了DDX21调控TGEV增殖的关键功能域。Western Blot分析显示,在TGEV WH-1株感染早期,PK-15细胞内源性DDX21蛋白的表达水平显著上调;RT-qPCR、Western Blot、IFA和TCID 50试验显示,超表达DDX21可以显著提高TGEV N基因的mRNA水平、N蛋白的表达及病毒滴度,且呈剂量依赖性,其601-784 aa区域是其影响TGEV复制的关键;与阴性对照相比,在相应DDX21敲低细胞系中TGEV的增殖显著被抑制,而回补试验逆转了DDX21敲低细胞系中TGEV的滴度。该研究首次揭示了猪DDX21对TGEV增殖的促进作用并鉴定了其调控TGEV复制的关键结构域,为今后研究DDX21蛋白的功能及TGEV的致病机理提供了理论依据。

Serologic and molecular survey for major viral pathogens in grazing hybrid wild boars in Northeast China

Hybrid wild boar husbandry is an important component of livestock production in Northeast China.However,the current disease situation of these animals is largely unknown due to a lack of disease surveillance.The present study was conducted to determine the prevalence of several important viral diseases in the hybrid wild boar population of Northeast China.Between September 2015 to December 2016,169 blood and 61 tissue samples were collected from apparently healthy hybrid wild boars from farms in Jilin,Inner Mongolia and Heilongjiang provinces.ELISA detected serum antibodies against classical swine fever virus(CSFV),porcine reproductive and respiratory syndrome virus(PRRSV),pseudorabies virus(PRV),porcine circovirus type 2(PCV2)and Japanese encephalitis virus(JEV),but not against African swine fever virus(ASFV),with PCV2 having the highest seropositive rate(87.2–100%in different farms).RT-PCR or PCR performed on the processed samples detected only PCV2,with 33.1%(56/169)of blood samples and 32.8%(20/61)of spleen samples being positive,respectively,indicating widespread PCV2 infection in hybrid wild boars.Phylogenetic analysis of 15 PCV2 ORF2 sequences showed that they belong to genotypes PCV2a,PCV2b and PCV2d,with nucleotide and deduced amino acid homologies of 88.5–100%and 88.1–100%,respectively.

Studies on Mucosal Immunity Induced by Transmissible Gastroenteritis Virus Nucleocapsid Protein Recombinant Lactobacillus casei in Mice and Sow

Mucosal immunity plays an important role in protecting pigs against transmissible gastroenteritis virus （TGEV） infection. To elicit mucosal immune response against TGEV, we developed a surface antigen display system using the poly-γ- glutamate synthetase A （pgsA） protein of Bacillus subtilis as an anchoring matrix to express recombinant fusion proteins of pgsA and nucleocapsid protein of TGEV in Lactobacillus casei. Surface location of fusion protein was verified by ELISA and indirect immunofluorescence test. Oral and intranasal inoculations of pregnant sow and mice with recombinant L. casei resulted in high levels of serum immunoglobulin G （IgG） and secretory immunoglobulin A （slgA） against recombinant N protein as demonstrated by ELISA. More importantly, the level of specific slgA in colostrum significantly increased compared with that of IgG. The serum IgG levels of the piglets increased after suckling colostrum produced by sows was previously inoculated with recombinant L. casei. These results indicate that immunization with recombinant L. casei expressing TGEV N protein on its surface elicited high levels of specific slgA and circulating IgG against TGEV N protein.

戊型肝炎病毒跨种间传播研究进展

戊型肝炎病毒(HEV)是病毒性肝炎的病原体,可经动物跨种间传播,其感染导致的戊型肝炎发病率居世界急性病毒性肝炎的首位,现已成为危害人类健康的主要公共健康问题。近年来,越来越多的物种被鉴定成为HEV新的天然宿主,HEV跨种间传播途径越来越多,严重阻碍了对该病毒的防控。因此,本文旨在总结、探讨HEV跨物种间传播的进展,为防控HEV的传播提供参考。

Phylogeography,Transmission,and Viral Proteins of Nipah Virus

Nipah virus (NiV), a zoonotic paramyxovirus belonging to the genus Henipavirus, is classified as a Biosafety Level-4 pathogen based on its high pathogenicity in humans and the lack of available vaccines or therapeutics. Since its initial emergence in 1998 in Malaysia, this virus has become a great threat to domestic animals and humans. Sporadic outbreaks and person-to-person transmission over the past two decades have resulted in hundreds of human fatalities. Epidemiological surveys have shown that NiV is distributed in Asia, Africa, and the South Pacific Ocean, and is transmitted by its natural reservoir, Pteropid bats. Numerous efforts have been made to analyze viral protein function and structure to develop feasible strategies for drug design. Increasing surveillance and preventative measures for the viral infectious disease are urgently needed.

圆圈病毒3型TaqMan荧光定量PCR检测方法的建立及应用

【目的】建立一种检测圆圈病毒3型(Gyrovirus 3,GyV3)的TaqMan荧光定量PCR方法,为GyV3提供快速便捷的检测技术手段。【方法】根据NCBI数据库中GyV3 VP2基因保守区序列,设计一对特异性检测引物和一条标记FAM荧光基团的探针,经过条件优化,建立用于检测GyV3的TaqMan实时荧光定量PCR快速检测方法,并进行特异性、敏感性、重复性以及模拟样品的检测试验。【结果】该方法灵敏性高,最低检测限度为1.585 copies·μL^(−1);特异性强,对其他常见禽病原不发生非特异性反应;重复性好,批内和批间变异系数均小于1%;对鸡肝脏组织DNA加入重组质粒制备的模拟样品同时进行TaqMan荧光定量PCR与SYBR GreenⅠ实时荧光定量PCR检测,均扩增出与预期相符的扩增曲线。【结论】首次建立用于检测GyV3的TaqMan实时荧光定量PCR快速检测方法,具有灵敏性高、特异性强、重复性好等优点,为GyV3的诊断和流行病学调查提供了技术支持。

影响鸡传染性病毒性腺胃炎人工发病模型建立的关键因素探讨

鸡传染性病毒性腺胃炎(TVP)是一种由病毒引起的慢性消耗性消化道疾病,其可导致典型腺胃炎症状。该病的临床症状多样、病因复杂,流行于多个国家,严重危害全球养鸡业的发展。明晰引起TVP发病的致病病因、建立其人工发病模型是研究该病发病机制及筛选有效防控剂的重要手段。鉴于此,本文对近年来TVP相关病原及其动物模型建立方面的研究进展进行综述,以期为该病的实验室研究及综合防控提供理论基础。

Nipah Virus: A Zoonotic Virus Transmitted from Bats and Pigs, Causing an Epidemic in Southeast Asia

Nipah Virus (NiV), a member of the Paramyxoviridae family, is one of the most infectious zoonotic viruses in Southeast Asia. First recorded in Malaysia in 1998, the NiV outbreak infected hundreds of people, with an almost 50% death rate. The virus is transmitted through direct contact with contaminated subjects and infecting the human respiratory system. Ephrin B2 and B3, the surface glycoproteins on the host cell, have been the primary and the most effective route for viral entrance. Binding with viral surface G protein, the F protein triggers, enabling viral-host fusion. Until now, NiV vaccines are not yet available in the public market, however, preventions such as avoiding direct contact and masking are advised.

乙肝母婴阻断停药后观察分析

目的探究乙型病毒性肝炎(乙肝)孕妇进行药物阻断停药后的肝功能变化情况。方法80例乙肝孕妇,随机分为观察组和对照组,每组40例。对照组孕妇不进行药物阻断,观察组孕妇于妊娠24~28周时开始进行药物阻断,于分娩后停药。比较两组入组时及分娩后1、3、6个月肝功能指标[谷草转氨酶(AST)、谷丙转氨酶(ALT)]水平、乙型肝炎病毒的脱氧核糖核酸(HBV-DNA)载量,观察组停药后1、3、6个月肝功能异常发生率。结果分娩后1、3、6个月,观察组AST水平分别为(22.42±6.54)、(28.22±6.44)、(29.60±6.34)U/L,明显低于对照组的(33.46±7.42)、(32.69±6.39)、(35.33±7.42)U/L,差异具有统计学意义(P<0.05)。分娩后1、3、6个月,观察组ALT水平分别为(16.56±6.59)、(21.13±6.59)、(22.56±6.92)U/L,明显低于对照组的(24.23±7.45)、(24.46±7.62)、(27.43±7.68)U/L,差异具有统计学意义(P<0.05)。分娩后1个月,观察组HBV-DNA载量为(5.94±0.38)log copies/ml,明显低于对照组的(7.39±0.52)log copies/ml,差异具有统计学意义(P<0.05);分娩后3、6个月,两组HBV-DNA载量比较差异无统计学意义(P>0.05)。观察组停药后1、3、6个月肝功能异常发生率分别为7.50%(3/40)、7.50%(3/40)、12.50%(5/40),比较差异无统计学意义(P>0.05)。结论替比夫定、替诺福韦可用于乙肝母婴阻断,可显著降低孕妇HBV-DNA载量,但停药后要注意按时进行复诊,避免肝功能指标及HBV-DNA载量水平升高。

一种新型肠传性病毒性肝炎的流行病学、临床、病理和病毒学的初步研究

背景单项血清肝酶增高的病因长期不明，某校学生中发生381例以此为主要特征的肝损害病人。目的为初步阐明这一疾病的病因、传播和病变。方法流行病学调查、临床观察、肝活组织检查以及血清和粪便的聚合酯链反应检测。结果根据临床和检测结果可排除中毒引起，已知肝炎病毒的血清标志物均明性。症状轻微，病程多急性、少数可超过6个月。肝组织呈汇管区炎。散在发病后进行3次人群普查，3个月累计发病率占流行人群的60．7％。分析认为经日常生活接触和多次小范围的食物传播。采取以切断传播为主的预防措施，2个月后流行控制。由病人的急性期血清和潜伏期粪便提取DNA，检出与一种新近报告的血传性病毒（TTV）有同源性的基因片段。结论可能是另一种肠传型肝炎病毒引起的非甲非戊型病毒性肝炎。

鸡传染性病毒性腺胃炎研究进展

鸡传染性病毒性腺胃炎是一种以腺胃肿大、腺胃乳头出血溃疡为主要特征的传染病,该病多发生于雏鸡,主要表现为生长停滞和消瘦,剖检除较常见的腺胃炎变化外,还可见胸腺和法氏囊萎缩,胰腺坏死。该病的临床症状、病理变化表现不尽相同,病原众说不一。文章就该病的病原学、流行病学、病理变化、临床症状以及鉴别诊断做了综述。

2015～2016年我国东北地区猪病毒性腹泻流行病学调查

为了解东北地区(黑龙江省、吉林省和辽宁省)的猪病毒性腹泻发病情况和流行特点,本研究对2015年~2016年间东北地区的88个疑似病毒性腹泻猪场进行临床症状、发病猪日龄、发病时间、发病率、病死率等基本情况调查,并采用RT-PCR和抗原快速检测试剂盒对送检疑似病毒性腹泻仔猪粪便或肠道内容物264份样品进行病原检测。调查结果显示,疫情多发生在冬春寒冷季节。发病初期,后备猪、母猪或育肥猪呈一过性腹泻,发病率一般在1%以下,腹泻主要发生于哺乳仔猪,发病率高达87.97%,病死率高达89.90%。3个省份的7日龄以内仔猪发病率分别为62.52%、79.73%和75.00%,病死率为84.91%、80.87%和80.25%。随着日龄的增加,仔猪的发病率和死亡率呈明显递减趋势。病原学检测结果显示,传染性胃肠炎病病毒(TGEV)的阳性率为6.06%(16/264),猪流行性腹泻病毒(PEDV)的阳性率为74.62%(197/264),猪轮状病病毒(PoRV)的阳性率为25.76%。其中,单一病原感染以PEDV最高,感染率为48.86%,Po RV感染率为1.52%,TGEV感染率为0.38%。存在TGEV/PEDV、TGEV/PoRV、PEDV/PoRV混合感染和PEDV/TGEV/PoRV的3重感染,以PEDV/Po RV的双重感染为主。结果表明,东北三省份的猪病毒性腹泻发病率和死亡率均较高,主要病原以PEDV为主。该调查结果为东北地区养殖场猪病毒性腹泻的综合防控提供流行病学数据。

天津市慢性丙型肝炎患者感染途径分析

目的分析天津市133例慢性丙型肝炎（丙肝）患者的感染途径，为丙肝的预防提供依据。方法2009～2012年天津市133例确诊为慢性丙型肝炎患者，通过患者的主诉确定丙肝的感染途径。采用FQ．PCR技术检测血清HCVRNA定量，对于HCVRNA定量〉1000IU／mL者参照文献采用基因芯片行HCVRNA基因型检测。应用全自动生化分析仪检测肝功能。结果133例慢性丙肝患者感染途径有输血及血制品76例，手术10例，牙齿治疗13例，穿耳洞、纹身13例，母婴传播1例，吸毒5例，不明原因15例。38例患者进行病毒基因型检测，1b型患者32例，2a型患者5例，3型患者1例。其中1b型患者输血或血制品感染18例，2a型患者输血或血制品感染4例。2000年之前经输血或血制品感染丙肝的感染率（84．1％）显著高于2000年及之后感染者（23．1％），P〈0．01（r=30．70），而2000年及之后感染者多数是经纹身、穿耳洞、吸毒等不良生活方式感染。输血及血制品感染者与非输血感染者的年龄分别为（53．84±10．94）、（42．70±12．71）岁，白蛋白（ALB）水平分别为（37．08±6．68）、（41．10±5．18）g／L，两者比较，P均〈0．01；病毒载量、丙氨酸氨基转氨酶（ALT）、总胆红素（TBIL）、甲胎蛋白（AFP）三指标在两者之间无统计学差异。不同年龄段慢性丙肝患者血清学指标比较，P均〉0．05。结论HCV感染者的感染途径包括经输血及血制品途径及经纹身、牙齿治疗、吸毒等非输血途径，病毒基因型多数为1b和2a型，对目前丙肝的主要感染途径进行有效阻断是防止丙肝感染的重要途径。