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Vitamin D-Regulated MicroRNAs: Are They Protective Factors against Dengue Virus Infection? 维生素d调控的microrna:它们是登革热病毒感染的保护因子吗?
IF 2.2 Q4 VIROLOGY Pub Date : 2016-01-01 Epub Date: 2016-05-11 DOI: 10.1155/2016/1016840
John F Arboleda, Silvio Urcuqui-Inchima

Over the last few years, an increasing body of evidence has highlighted the critical participation of vitamin D in the regulation of proinflammatory responses and protection against many infectious pathogens, including viruses. The activity of vitamin D is associated with microRNAs, which are fine tuners of immune activation pathways and provide novel mechanisms to avoid the damage that arises from excessive inflammatory responses. Severe symptoms of an ongoing dengue virus infection and disease are strongly related to highly altered production of proinflammatory mediators, suggesting impairment in homeostatic mechanisms that control the host's immune response. Here, we discuss the possible implications of emerging studies anticipating the biological effects of vitamin D and microRNAs during the inflammatory response, and we attempt to extrapolate these findings to dengue virus infection and to their potential use for disease management strategies.

在过去几年中,越来越多的证据强调了维生素D在调节促炎反应和抵御包括病毒在内的许多感染性病原体方面的重要作用。维生素D的活性与microrna有关,microrna是免疫激活途径的精细调节者,并提供了避免过度炎症反应引起的损伤的新机制。持续的登革热病毒感染和疾病的严重症状与促炎介质产生的高度改变密切相关,这表明控制宿主免疫反应的稳态机制受损。在这里,我们讨论了在炎症反应中预测维生素D和microrna的生物学效应的新兴研究的可能含义,我们试图将这些发现推断为登革热病毒感染及其在疾病管理策略中的潜在应用。
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引用次数: 21
Expression of Factor X in BHK-21 Cells Promotes Low Pathogenic Influenza Viruses Replication BHK-21细胞表达因子X促进低致病性流感病毒复制
IF 2.2 Q4 VIROLOGY Pub Date : 2015-12-31 DOI: 10.1155/2015/675921
S. Shahsavandi, M. Ebrahimi, S. Masoudi, H. Izadi
A cDNA clone for factor 10 (FX) isolated from chicken embryo inserted into the mammalian cell expression vector pCDNA3.1 was transfected into the baby hamster kidney (BHK-21) cell line. The generated BHK-21 cells with inducible expression of FX were used to investigate the efficacy of the serine transmembrane protease to proteolytic activation of influenza virus hemagglutinin (HA) with monobasic cleavage site. Data showed that the BHK-21/FX stably expressed FX after ten serial passages. The cells could proteolytically cleave the HA of low pathogenic avian influenza virus at multiplicity of infection 0.01. Growth kinetics of the virus on BHK-21/FX, BHK-21, and MDCK cells were evaluated by titrations of virus particles in each culture supernatant. Efficient multicycle viral replication was markedly detected in the cell at subsequent passages. Virus titration demonstrated that BHK-21/FX cell supported high-titer growth of the virus in which the viral titer is comparable to the virus grown in BHK-21 or MDCK cells with TPCK-trypsin. The results indicate potential application for the BHK-21/FX in influenza virus replication procedure and related studies.
将鸡胚分离的因子10 (FX) cDNA克隆插入哺乳动物细胞表达载体pCDNA3.1中,转染到幼鼠肾(BHK-21)细胞系中。利用诱导表达FX的BHK-21细胞,研究丝氨酸跨膜蛋白酶对具有单基裂解位点的流感病毒血凝素(HA)蛋白水解激活的效果。数据显示,BHK-21/FX在连续10次传代后稳定表达FX。在感染倍数为0.01的情况下,细胞能蛋白裂解低致病性禽流感病毒的HA。病毒在BHK-21/FX、BHK-21和MDCK细胞上的生长动力学通过每个培养上清中病毒颗粒的滴定来评估。在随后的传代中,细胞中明显检测到高效的多周期病毒复制。病毒滴度测定表明,BHK-21/FX细胞支持病毒的高滴度生长,其病毒滴度与在BHK-21或MDCK细胞中生长的病毒滴度相当。结果提示BHK-21/FX在流感病毒复制过程及相关研究中的潜在应用。
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引用次数: 2
Antiviral Activity of Resveratrol against Human and Animal Viruses 白藜芦醇对人、动物病毒的抗病毒活性研究
IF 2.2 Q4 VIROLOGY Pub Date : 2015-11-29 DOI: 10.1155/2015/184241
Y. Abba, H. Hassim, H. Hamzah, M. Noordin
Resveratrol is a potent polyphenolic compound that is being extensively studied in the amelioration of viral infections both in vitro and in vivo. Its antioxidant effect is mainly elicited through inhibition of important gene pathways like the NF-κβ pathway, while its antiviral effects are associated with inhibitions of viral replication, protein synthesis, gene expression, and nucleic acid synthesis. Although the beneficial roles of resveratrol in several viral diseases have been well documented, a few adverse effects have been reported as well. This review highlights the antiviral mechanisms of resveratrol in human and animal viral infections and how some of these effects are associated with the antioxidant properties of the compound.
白藜芦醇是一种有效的多酚化合物,在体外和体内都被广泛研究用于改善病毒感染。其抗氧化作用主要通过抑制NF-κβ通路等重要基因通路而发挥,而其抗病毒作用则与抑制病毒复制、蛋白合成、基因表达、核酸合成等有关。尽管白藜芦醇在几种病毒性疾病中的有益作用已被充分证明,但也有一些不良反应被报道。本文综述了白藜芦醇在人类和动物病毒感染中的抗病毒机制,以及这些作用与该化合物的抗氧化特性之间的关系。
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引用次数: 124
Clinical Symptoms of Human Rotavirus Infection Observed in Children in Sokoto, Nigeria 尼日利亚索科托儿童轮状病毒感染的临床症状
IF 2.2 Q4 VIROLOGY Pub Date : 2015-11-25 DOI: 10.1155/2015/890957
B. Alkali, A. Daneji, A. A. Magaji, L. S. Bilbis
Rotavirus has been identified among the most important causes of infantile diarrhoea, especially in developing countries. The present study was undertaken to determine the occurrence and clinical symptoms of human rotavirus disease among children presenting with varying degree of diarrhoea in selected urban hospitals in Sokoto metropolis, Nigeria. Diarrhoea samples were collected from 200 diarrheic children younger than 5 years of age and tested using a commercially available DAKO Rotavirus ELISA kit which detects the presence of human group A rotaviruses. A questionnaire, based on WHO generic protocol, was completed for each child to generate the primary data. Of the total number of samples collected, 51 were found to be positive for human group A rotavirus indicating 25.5% prevalence of the disease in Sokoto state. The symptoms associated with the disease were analyzed and discussed.
轮状病毒已被确定为婴儿腹泻的最重要原因之一,特别是在发展中国家。本研究旨在确定尼日利亚索科托大都会若干城市医院中出现不同程度腹泻的儿童中人类轮状病毒病的发生情况和临床症状。收集了200名5岁以下腹泻儿童的腹泻样本,并使用市售的DAKO轮状病毒ELISA试剂盒进行检测,该试剂盒可检测人类a群轮状病毒的存在。根据世卫组织通用方案,为每个儿童填写了一份问卷,以产生主要数据。在所收集的样本总数中,发现51个人类A组轮状病毒呈阳性,表明索科托州的患病率为25.5%。对与该病相关的症状进行了分析和讨论。
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引用次数: 19
Evaluating Andrographolide as a Potent Inhibitor of NS3-4A Protease and Its Drug-Resistant Mutants Using In Silico Approaches 利用计算机方法评价穿心莲内酯作为NS3-4A蛋白酶的有效抑制剂及其耐药突变体
IF 2.2 Q4 VIROLOGY Pub Date : 2015-10-26 DOI: 10.1155/2015/972067
V. Chandramohan, Anubhav Kaphle, Mamatha Chekuri, Sindhu Gangarudraiah, Gowrishankar Bychapur Siddaiah
Current combination therapy of PEG-INF and ribavirin against the Hepatitis C Virus (HCV) genotype-1 infections is ineffective in maintaining sustained viral response in 50% of the infection cases. New compounds in the form of protease inhibitors can complement the combination therapy. Asunaprevir is new to the drug regiment as the NS3-4A protease inhibitor, but it is susceptible to two mutations, namely, R155K and D168A in the protein. Thus, in our study, we sought to evaluate Andrographolide, a labdane-diterpenoid from the Andrographis paniculata plant as an effective compound for inhibiting the NS3-4A protease as well as its concomitant drug-resistant mutants by using molecular docking and dynamic simulations. Our study shows that Andrographolide has best docking scores of −15.0862, −15.2322, and −13.9072 compared to those of Asunaprevir −3.7159, −2.6431, and −5.4149 with wild-type R155K and D168A mutants, respectively. Also, as shown in the MD simulations, the compound was good in binding the target proteins and maintains strong bonds causing very less to negligible perturbation in the protein backbone structures. Our results validate the susceptibility of Asunaprevir to protein variants as seen from our docking studies and trajectory period analysis. Therefore, from our study, we hope to add one more option in the drug regiment to tackle drug resistance in HCV infections.
目前PEG-INF和利巴韦林联合治疗丙型肝炎病毒(HCV)基因型1感染对50%的感染病例维持持续的病毒应答无效。蛋白酶抑制剂形式的新化合物可以补充联合治疗。作为NS3-4A蛋白酶抑制剂,Asunaprevir是新加入药物团的药物,但易受蛋白R155K和D168A两种突变的影响。因此,在我们的研究中,我们试图通过分子对接和动态模拟来评估穿心莲内酯是一种从穿心莲植物中提取的双萜,作为抑制NS3-4A蛋白酶及其伴随的耐药突变体的有效化合物。研究表明,与Asunaprevir的- 3.7159、- 2.6431和- 5.4149相比,穿心莲内酯与野生型R155K和D168A的对接分数分别为- 15.0862、- 15.2322和- 13.9072。此外,如MD模拟所示,该化合物与靶蛋白结合良好,并保持强键,对蛋白质骨干结构的扰动很小,甚至可以忽略不计。我们的研究结果证实了Asunaprevir对蛋白质变异的易感性,这是我们对接研究和轨迹周期分析所看到的。因此,从我们的研究中,我们希望在药物团中增加一个选择来解决HCV感染的耐药性。
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引用次数: 33
Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis 麻疹病毒:亚急性硬化性全脑炎潜在分子标志物M蛋白一级序列的鉴定
IF 2.2 Q4 VIROLOGY Pub Date : 2015-10-26 DOI: 10.1155/2015/769837
Hasan Kweder, M. Ainouze, J. Brunel, D. Gerlier, E. Manet, R. Buckland
Subacute Sclerosing Panencephalitis (SSPE), a rare lethal disease of children and young adults due to persistence of measles virus (MeV) in the brain, is caused by wild type (wt) MeV. Why MeV vaccine strains never cause SSPE is completely unknown. Hypothesizing that this phenotypic difference could potentially be represented by a molecular marker, we compared glycoprotein and matrix (M) genes from SSPE cases with those from the Moraten vaccine strain, searching for differential structural motifs. We observed that all known SSPE viruses have residues P64, E89, and A209 (PEA) in their M proteins whereas the equivalent residues for vaccine strains are either S64, K89, and T209 (SKT) as in Moraten or PKT. Through the construction of MeV recombinants, we have obtained evidence that the wt MeV-M protein PEA motif, in particular A209, is linked to increased viral spread. Importantly, for the 10 wt genotypes (of 23) that have had their M proteins sequenced, 9 have the PEA motif, the exception being B3, which has PET. Interestingly, cases of SSPE caused by genotype B3 have yet to be reported. In conclusion, our results strongly suggest that the PEA motif is a molecular marker for wt MeV at risk to cause SSPE.
亚急性硬化性全脑炎(SSPE)是由野生型(wt)麻疹病毒引起的,是儿童和年轻人中一种罕见的致命性疾病,由麻疹病毒(MeV)在大脑中持续存在引起。为什么MeV疫苗株不会引起SSPE完全未知。假设这种表型差异可能由分子标记来表示,我们比较了SSPE病例和Moraten疫苗株的糖蛋白和基质(M)基因,寻找不同的结构基板。我们观察到所有已知的SSPE病毒在其M蛋白中都有P64、E89和A209 (PEA)残基,而疫苗株的等效残基为S64、K89和T209 (SKT),如Moraten或PKT中的残基。通过构建MeV重组体,我们已经获得了wt MeV- m蛋白PEA基序,特别是A209,与病毒传播增加有关的证据。重要的是,对10个wt基因型(23个)进行了M蛋白测序,其中9个具有PEA基序,除了B3,它具有PET。有趣的是,由B3基因型引起的SSPE病例尚未报道。总之,我们的研究结果强烈表明PEA基序是有SSPE风险的wt MeV的分子标记。
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引用次数: 14
Seroprevalence of Herpes Simplex Virus Infection in HIV Coinfected Individuals in Eastern India with Risk Factor Analysis 印度东部HIV合并感染者血清单纯疱疹病毒感染的患病率及危险因素分析
IF 2.2 Q4 VIROLOGY Pub Date : 2015-10-19 DOI: 10.1155/2015/537939
S. Nag, Soma Sarkar, Debprasad Chattopadhyay, S. Bhattacharya, R. Biswas, M. Sengupta
Herpes simplex virus type 2 (HSV-2) is the cause of most genital herpes while HSV-1 is responsible for orolabial and facial lesions. In immunocompromised individuals, like HIV patients, impaired immunity leads to more frequent symptomatic and asymptomatic HSV infection. Fifty-two blood samples from HIV patients with clinically diagnosed HSV infection were taken as cases, while 45 blood samples each from HIV-infected (HIV control) and noninfected patients without any herpetic lesion (non-HIV control) were taken as control. Serum was tested for IgM and IgG antibodies of both HSV-1 and HSV-2 by ELISA. The seroprevalence was compared among the three groups of study population, considering the demographic and socioeconomic parameters. The HSV-2 IgM was significantly higher (p < 0.005) in the HIV patient group (34.6%) than the HIV control (2.2%) and non-HIV control (2.2%) groups, whereas HSV-2 IgG seroprevalence was higher in both HIV patient (61.5%) and HIV control (57.8%) groups than the non-HIV control group (17.8%). The prevalence of HSV-2 was significantly higher in persons with multiple partners and in the reproductive age group. The overall seroprevalence of HSV-1 IgM was too low (<5%), whereas it was too high (about 90%) with HSV-1 IgG in all three study groups.
单纯疱疹病毒2型(HSV-2)是大多数生殖器疱疹的病因,而单纯疱疹病毒1型是口腔和面部病变的原因。在免疫功能低下的个体中,如艾滋病毒患者,免疫力受损导致更频繁的有症状和无症状的HSV感染。将临床诊断为HSV感染的HIV患者的52份血样作为病例,将HIV感染者(HIV对照组)和未感染且无疱疹性病变的患者(非HIV对照组)各45份血样作为对照。采用ELISA法检测血清中HSV-1和HSV-2的IgM和IgG抗体。考虑人口统计学和社会经济参数,比较三组研究人群的血清阳性率。HIV患者组HSV-2 IgM阳性率(34.6%)显著高于HIV对照组(2.2%)和非HIV对照组(2.2%),而HIV患者组(61.5%)和HIV对照组(57.8%)血清HSV-2 IgG阳性率均高于非HIV对照组(17.8%)。2型单纯疱疹病毒在有多个性伴侣和育龄人群中的流行率明显较高。在所有三个研究组中,HSV-1 IgM的总体血清阳性率过低(<5%),而HSV-1 IgG的总体血清阳性率过高(约90%)。
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引用次数: 16
Nelfinavir impairs glycosylation of herpes simplex virus 1 envelope proteins and blocks virus maturation. 奈非那韦会损害单纯疱疹病毒1包膜蛋白的糖基化并阻止病毒成熟。
IF 2.2 Q4 VIROLOGY Pub Date : 2015-01-01 Epub Date: 2015-01-29 DOI: 10.1155/2015/687162
Soren Gantt, Eliora Gachelet, Jacquelyn Carlsson, Serge Barcy, Corey Casper, Michael Lagunoff

Nelfinavir (NFV) is an HIV-1 aspartyl protease inhibitor that has numerous effects on human cells, which impart attractive antitumor properties. NFV has also been shown to have in vitro inhibitory activity against human herpesviruses (HHVs). Given the apparent absence of an aspartyl protease encoded by HHVs, we investigated the mechanism of action of NFV herpes simplex virus type 1 (HSV-1) in cultured cells. Selection of HSV-1 resistance to NFV was not achieved despite multiple passages under drug pressure. NFV did not significantly affect the level of expression of late HSV-1 gene products. Normal numbers of viral particles appeared to be produced in NFV-treated cells by electron microscopy but remain within the cytoplasm more often than controls. NFV did not inhibit the activity of the HSV-1 serine protease nor could its antiviral activity be attributed to inhibition of Akt phosphorylation. NFV was found to decrease glycosylation of viral glycoproteins B and C and resulted in aberrant subcellular localization, consistent with induction of endoplasmic reticulum stress and the unfolded protein response by NFV. These results demonstrate that NFV causes alterations in HSV-1 glycoprotein maturation and egress and likely acts on one or more host cell functions that are important for HHV replication.

奈非那韦(Nelfinavir,NFV)是一种 HIV-1 天冬氨酰蛋白酶抑制剂,对人体细胞有多种作用,具有诱人的抗肿瘤特性。NFV 还被证明对人类疱疹病毒(HHV)具有体外抑制活性。鉴于 HHVs 明显缺乏天冬氨酰蛋白酶,我们研究了 NFV 在培养细胞中对单纯疱疹病毒 1 型(HSV-1)的作用机制。尽管在药物压力下进行了多次传代,但仍未发现 HSV-1 对 NFV 产生耐药性。NFV 对后期 HSV-1 基因产物的表达水平没有明显影响。通过电子显微镜观察,NFV处理过的细胞似乎产生了正常数量的病毒颗粒,但与对照组相比,病毒颗粒更多地停留在细胞质中。NFV 不能抑制 HSV-1 丝氨酸蛋白酶的活性,其抗病毒活性也不能归因于抑制 Akt 磷酸化。研究发现,NFV 会降低病毒糖蛋白 B 和 C 的糖基化,并导致亚细胞定位异常,这与 NFV 诱导内质网应激和未折叠蛋白反应是一致的。这些结果表明,NFV 会改变 HSV-1 糖蛋白的成熟和排出,并可能影响对 HHV 复制很重要的一种或多种宿主细胞功能。
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引用次数: 0
Farming of Plant-Based Veterinary Vaccines and Their Applications for Disease Prevention in Animals. 植物性兽用疫苗的养殖及其在动物疾病预防中的应用。
IF 2.2 Q4 VIROLOGY Pub Date : 2015-01-01 Epub Date: 2015-08-13 DOI: 10.1155/2015/936940
Pit Sze Liew, Mohd Hair-Bejo

Plants have been studied for the production of pharmaceutical compounds for more than two decades now. Ever since the plant-made poultry vaccine against Newcastle disease virus made a breakthrough and went all the way to obtain regulatory approval, research to use plants for expression and delivery of vaccine proteins for animals was intensified. Indeed, in view of the high production costs of veterinary vaccines, plants represent attractive biofactories and offer many promising advantages in the production of recombinant vaccine proteins. Furthermore, the possibility of conducting immunogenicity and challenge studies in target animals has greatly exaggerated the progress. Although there are no edible plant-produced animal vaccines in the market, plant-based vaccine technology has great potentials. In this review, development, uses, and advantages of plant-based recombinant protein production in various expression platforms are discussed. In addition, examples of plant-based veterinary vaccines showing strong indication in terms of efficacy in animal disease prevention are also described.

二十多年来,人们一直在研究如何利用植物生产药物化合物。自从植物制成的家禽新城疫病毒疫苗取得突破性进展并获得监管部门批准后,利用植物表达和输送动物疫苗蛋白的研究就得到了加强。事实上,鉴于兽用疫苗的生产成本较高,植物是极具吸引力的生物工厂,在生产重组疫苗蛋白方面具有许多有前景的优势。此外,在目标动物身上进行免疫原性和挑战性研究的可能性也极大地推动了这一进程。虽然目前市场上还没有可食用的植物生产的动物疫苗,但植物疫苗技术具有巨大的潜力。本综述讨论了各种表达平台中植物重组蛋白生产的发展、用途和优势。此外,还介绍了在动物疾病预防方面显示出强大功效的植物兽用疫苗实例。
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引用次数: 0
Comparison of β-Propiolactone and Formalin Inactivation on Antigenicity and Immune Response of West Nile Virus. β-丙内酯与福尔马林灭活对西尼罗病毒抗原性和免疫应答的影响比较。
IF 2.2 Q4 VIROLOGY Pub Date : 2015-01-01 Epub Date: 2015-08-27 DOI: 10.1155/2015/616898
Pritom Chowdhury, Rashmee Topno, Siraj A Khan, Jagadish Mahanta

West Nile Virus (WNV) is a pathogenic arbovirus that belongs to genus Flavivirus under family Flaviviridae. Till now there are no approved vaccines against WNV for human use. In this study, the effect of two alkylating agents, formaldehyde and β-PL, generally used for inactivated vaccine preparation, was assessed on the basis of antigenic and immunogenic potential of the inactivated WNV. Lineage 5 WNV isolates were inactivated by both formalin and β-PL treatments. Inactivation was confirmed by repeated passage in BHK-21 cell line and infant mice. Viruses inactivated by both the treatments showed higher antigenicity. Immune response in mice model showed serum anti-WNV antibody titre was moderately higher in formalin inactivated antigen compared to β-PL inactivated antigen. However, no significant differences were observed in neutralization antibody titre. In conclusion, we can state that both formaldehyde and β-PL inactivation processes were found to be equally efficient for inactivation of WNV. However, they need to be compared with other inactivating agents along with study on cell mediated immune response.

西尼罗河病毒(WNV)是黄病毒科黄病毒属的一种致病性虫媒病毒。到目前为止,还没有批准用于人类的西尼罗河病毒疫苗。本研究以灭活西尼罗河病毒的抗原性和免疫原性为基础,评价了常用灭活疫苗制备的两种烷基化剂甲醛和β-PL的效果。5系WNV分离株经福尔马林和β-PL处理均失活。在BHK-21细胞系和幼鼠中反复传代证实失活。两种处理灭活的病毒均表现出较高的抗原性。小鼠免疫反应模型显示,福尔马林灭活抗原血清抗西尼罗病毒抗体滴度高于β-PL灭活抗原。然而,中和抗体滴度无显著差异。总之,我们可以声明,甲醛和β-PL失活过程被发现对西尼罗河病毒的失活同样有效。然而,它们需要与其他灭活剂进行比较,并研究细胞介导的免疫反应。
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引用次数: 14
期刊
Advances in Virology
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