BACKGROUND & AIMS: :Few details are known about how the human immunodeficiency virus type 1 (HIV-1) genomic RNA is trafficked in the cytoplasm. Part of this process is controlled by the activity of heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2). The role of hnRNP A2 during the expression of a bona fide provirus in HeLa cells is investigated in this study. Using immunofluorescence and fluorescence in situ hybridization techniques, we show that knockdown of hnRNP A2 expression in HIV-1-expressing cells results in the rapid accumulation of HIV-1 genomic RNA in a distinct, cytoplasmic space that corresponds to the microtubule-organizing center (MTOC). The RNA exits in the nucleus and accumulates at the MTOC region as a result of hnRNP A2 knockdown even during the expression of a provirus harboring mutations in the hnRNP A2-response element (A2RE), the expression of which results in nuclear retention of genomic RNA. We also demonstrate that hnRNP A2 expression is required for downstream trafficking of genomic RNA from the MTOC in the cytoplasm. Genomic RNA localization at the MTOC that was both the result of hnRNP A2 knockdown and the overexpression of Rab7-interacting lysosomal protein had little effect on pr55Gag synthesis but negatively influenced virus production and infectivity. These data indicate that altered HIV-1 genomic RNA localization modulates viral assembly and that the MTOC serves as a central site to which HIV-1 genomic RNA converges following its exit from the nucleus, with the host protein, hnRNP A2, playing a central role in taking it to and from this site in the cell.

背景与目标： : 关于人类免疫缺陷病毒1型 (HIV-1) 基因组RNA如何在细胞质中运输的细节知之甚少。该过程的一部分受异质核核糖核蛋白A2 (hnRNP A2) 的活性控制。本研究研究了hnRNP A2在HeLa细胞中真正的前病毒表达中的作用。使用免疫荧光和荧光原位杂交技术，我们显示了HIV-1-expressing细胞中hnRNP A2表达的敲低导致HIV-1基因组RNA在与微管组织中心 (MTOC) 相对应的独特细胞质空间中快速积累。即使在hnRNP A2-response元件 (A2RE) 中携带突变的前病毒的表达过程中，由于hnRNP A2敲除，RNA也会在细胞核中离开并在MTOC区域积累，其表达导致基因组RNA的核保留。我们还证明hnRNP A2表达是细胞质中来自MTOC的基因组RNA下游运输所必需的。hnRNP A2敲低的结果和Rab7-interacting溶酶体蛋白的过表达在MTOC上的基因组RNA定位对pr55Gag的合成几乎没有影响，但对病毒的产生和感染性产生负面影响。这些数据表明，改变的HIV-1基因组RNA定位调节病毒组装，并且MTOC充当HIV-1基因组RNA从细胞核退出后会聚的中心位点，宿主蛋白hnrnpa2在将其带到和从细胞中的该位点中起着核心作用。

BACKGROUND & AIMS: :The aim of this study is to find out the causes of skin diseases in one-third of the staff of a perfume factory, in which 10 different perfume sprays were being manufactured. Site inspection, dermatological examination and patch testing of all 26 persons at risk with 4 perfume oils and 30 ingredients of them. The results showed 6 bottlers were found suffering from allergic contact dermatitis, 2 from irritant contact dermatitis, 12 workers showed different strong reactions to various fragrances. The main causes of allergic contact dermatitis were 2 perfume oils (12 cases) and their ingredients geraniol (12 cases), benzaldehyde(9), cinnamic aldehyde (6), linalool, neroli oil, terpenes of lemon oil and orange oil (4 each). Nobody was tested positive to balsam of Peru. Job changes for office workers, packers or printers to other rooms, where they had no longer contact with fragrances, led to a settling. To conclude, automation and replacement of glass bottles by cartridges from non-fragile materials and using gloves may minimize the risk.

背景与目标： : 这项研究的目的是找出3分之1一家香水工厂的工作人员的皮肤病的原因，该工厂生产了10种不同的香水喷雾剂。现场检查，皮肤科检查和所有26名有风险的人使用4种香料油和30种成分进行贴剂测试。结果显示，6名装瓶工人患有过敏性接触性皮炎，2名来自刺激性接触性皮炎，12名工人对各种香料表现出不同的强烈反应。过敏性接触性皮炎的主要病因为香精油2种 (12例)，其成分为香叶醇 (12例)，苯甲醛 (9例)，肉桂醛 (6例)，芳樟醇，橙花油，柠檬油和橙油的萜烯 (4例)。没有人对秘鲁的香脂测试呈阳性。办公室工作人员，包装工或打印机的工作变更到其他房间，他们不再与香水接触，导致了定居。总而言之，用非易碎材料和使用手套的墨盒自动化和更换玻璃瓶可以最大程度地降低风险。

BACKGROUND & AIMS: :Seventy-two patients with tumor and ten with non-neoplastic colon disease were studied for the presence of estrogen receptors (ER) by three different methods. Only seven specimens (six primary adenocarcinomas and one recurrent cancer) had an ER concentration above 3 fm/mg of cytosolic protein, with no sex, age and tumor stage correlation. Our results suggest that the large bowel does not contain a cytosolic receptor for estradiol.

背景与目标： : 通过三种不同的方法研究了72例肿瘤患者和10例非肿瘤性结肠疾病的雌激素受体 (ER) 的存在。只有7个标本 (6个原发性腺癌和1个复发性癌症) 的ER浓度高于3 fm/mg的胞质蛋白，没有性别，年龄和肿瘤分期的相关性。我们的结果表明，大肠不含雌二醇的胞质受体。

BACKGROUND & AIMS: INTRODUCTION:STDs are a significant cause of illness throughout the world. Female sex workers (FSWs) are commonly perceived as belonging to a social group which may engage in high-risk behaviour for acquiring or transmitting HIV and other STDs. The number of immigrant women engaged in sex work has increased in Catania, Sicily, over the last 10 years. This study aims to estimate the prevalence of HIV, HBV, HCV and syphilis among Colombian and Dominican FSWs. METHODS:In total 118 (63.78%) of the FSWs contacted in the course of the project agreed to participate in the study. All women enrolled were counselled on STDs/HIV, safer sex practices and the use of condoms. Blood samples were taken and tested for HIV, HBV, HCV and syphilis. RESULTS:Of the 118 FSWs enrolled, all were negative for both HIV and HCV infection. Two women (1.6%) were positive for hepatitis B (HbsAg). Syphilis testing by VDRL showed three positive results (2.5%), which was confirmed by TPHA. DISCUSSION:This study showed that HIV, HBV, HCV and syphilis seroprevalence among Colombian and Dominican FSWs remains low or very rare. It also indicates that these women were healthy when they arrived in Italy and that condom use with clients is high.

背景与目标：

BACKGROUND & AIMS: :IL-7 signals are crucial for the survival of naive and memory T cells, and the IL-7R is expressed on the surface of these cells. Following viral infection, the IL-7R is expressed on only a subset of effector CD8 T cells, and has been demonstrated to be important for the survival of these memory precursors. IL-7 message levels remain relatively constant during the T cell response to lymphocytic choriomeningitis virus, but a short-lived burst of GM-CSF is observed soon after infection. Retroviral expression of a chimeric GM-CSF/IL-7R, in which binding of GM-CSF by T cells leads to IL-7 signaling, allows for the delivery of an IL-7 signal in all effector T cells expressing the receptor. In mice infected with lymphocytic choriomeningitis virus, CD8 and CD4 T cells transduced with this chimeric receptor underwent an enhanced proliferative response compared with untransduced populations in the same host. Similarly, TCR transgenic CD8 cells expressing the chimeric receptor produced higher effector numbers during the peak of the T cell response to infection. Surprisingly, the enhanced proliferation did not lead to higher memory numbers, as the subsequent contraction phase was more pronounced in the transduced cell populations. These findings demonstrate that artificial IL-7 signaling during an infection leads to significantly increased Ag-specific effector T cell numbers, but does not result in increased numbers of memory progeny. The extent of contraction may be dictated by intrinsic factors related to the number of prior cell divisions.

背景与目标： : IL-7信号对于幼稚和记忆T细胞的存活至关重要，并且IL-7R在这些细胞的表面表达。病毒感染后，该IL-7R仅在效应cd8t细胞的子集上表达，并且已被证明对这些记忆前体的存活很重要。在T细胞对淋巴细胞性脉络丛脑膜炎病毒的反应期间，IL-7信息水平保持相对恒定，但是在感染后不久就观察到gm-csf的短暂爆发。嵌合gm-csf/IL-7R的逆转录病毒表达允许在表达该受体的所有效应T细胞中递送IL-7信号，其中gm-csf被T细胞结合导致IL-7信号。在感染了淋巴细胞性脉络丛脑膜炎病毒的小鼠中，与同一宿主中未转导的人群相比，用该嵌合受体转导的CD8和CD4 T细胞的增殖反应增强。同样，表达嵌合受体的TCR转基因CD8细胞在T细胞对感染的反应高峰期间产生更高的效应子数。令人惊讶的是，增强的增殖并未导致更高的记忆数，因为随后的收缩阶段在转导的细胞群体中更为明显。这些发现表明，感染期间的人工IL-7信号传导导致Ag特异性效应T细胞数量显着增加，但不会导致记忆后代数量增加。收缩的程度可能取决于与先前细胞分裂数量相关的内在因素。

BACKGROUND & AIMS: OBJECTIVES:To describe the prevalence of oral diseases and their impact on oral-health-related quality of life in people with severe mental illness undertaking community-based psychiatric care. METHODS:A survey was conducted at eight outpatient psychiatric care clinics in Tower Hamlets, London, UK. One hundred and twelve consecutive patients with mental illness were invited to participate in this study. They were clinically examined and asked to complete the oral health impact profile (OHIP) questionnaire. RESULTS:The response rate was 79% (n = 89); 57 (64%) males and 58 persons over 45 years of age (65%) participated in this survey. Overall OHIP score was 25.4 (95% CI 23.3, 27.4), 70 (78%) were smokers and 45 (51%) had been to the dentist in the last two years. Forty-seven (53%) respondents had caries in at least one tooth, 60 (67%) had 21 teeth and more, and 14 (16%) used dentures. Advanced periodontal treatment was indicated in 42 (55%) of patients and 52.8% (n = 47) patients reported current pain. CONCLUSION:Overall, this survey found that oral health has a great impact on patients with severe mental illness being treated in the community setting and their oral health is poorer than the national adult general population. Future research should consider the causes that relate to the poorer oral health in this population and potential health promotion mechanisms in this population to encourage an upstream approach to health.

背景与目标：

BACKGROUND & AIMS: :From 1982 to 1987, 2,433 lesions of the thyroid gland in 1,796 patients were examined by fine needle aspiration (FNA). Cytopathology classified 66.91% of the aspirates as benign, 10.76% as thyroiditis, 4.89% as suspected (unspecified) neoplasia, 1.31% as positive for malignancy and 16.11% (392) as unsatisfactory. The histologic diagnoses in 257 cases were compared with cytologic diagnoses to determine the accuracy of FNA cytology of thyroid lesions, yielding a sensitivity of 71.43%, a specificity of 100% and an accuracy of 95.09%. This data strongly supports thyroid FNA as an important preoperative diagnostic tool. Follicular carcinomas were difficult to cytologically differentiate from nonmalignant follicular neoplasms, and papillary thyroid carcinomas less than 2 cm in diameter in elderly patients were frequently misdiagnosed or diagnosed only as "suspect lesion."

背景与目标： : 从1982个1987年中，通过细针穿刺 (FNA) 检查了1,796例患者的2,433个甲状腺病变。细胞病理学将66.91% 抽吸物分类为良性，10.76% 为甲状腺炎，4.89% 为疑似 (未指定) 肿瘤，1.31% 为恶性肿瘤阳性，16.11% (392) 为不满意。将257例的组织学诊断与细胞学诊断进行比较，以确定甲状腺病变的FNA细胞学检查的准确性，从而产生71.43% 的敏感性，100% 的特异性和95.09% 的准确性。该数据强烈支持甲状腺FNA作为重要的术前诊断工具。滤泡癌在细胞学上很难与非恶性滤泡肿瘤区分开来，而老年患者直径小于2厘米的甲状腺乳头状癌经常被误诊或仅被诊断为 “可疑病变”。

BACKGROUND & AIMS: :Mutations in the senataxin (SETX) gene can cause amyotrophic lateral sclerosis 4 (ALS4), an autosomal dominant form of juvenile onset amyotrophic lateral sclerosis, or result in autosomal recessive ataxia with oculomotor apraxia type 2. Great caution regarding the possible disease causation, especially of missense variations, has to be taken. Here, we evaluated the significance of all previously reported SETX missense mutations as well as six newly identified variations in 54 patients suspected of having ALS4. Yet, epidemiologic and in silico evidence indicates that all newly identified variations and two previously published ALS4-related missense variations (C1554G and I2547T) are most likely non-pathogenic, demonstrating the problems of interpretation of SETX missense alleles in the absence of functional assays.

背景与目标： : senataxin (SETX) 基因的突变可导致肌萎缩性侧索硬化症4 (ALS4)，这是一种常染色体显性遗传形式的少年性肌萎缩性侧索硬化症，或导致常染色体隐性遗传性共济失调并伴有动眼失用2型。对于可能的疾病原因，尤其是错义变异，必须谨慎行事。在这里，我们评估了所有先前报道的SETX错义突变以及54例怀疑患有als4的患者中新发现的六个变异的重要性。然而，流行病学和计算机证据表明，所有新发现的变异和两个先前发表的ALS4-related错义变异 (C1554G和I2547T) 最有可能是非致病性的，证明了在缺乏功能测定的情况下解释SETX错义等位基因的问题。

BACKGROUND & AIMS: :The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38α MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release. For reconfirming the findings of the animal studies when administering 1 to healthy human volunteers, a phase I clinical trial was conducted. Apart from further information regarding the pharmacokinetic and pharmacodynamic characteristics of 1, it was demonstrated that dual inhibition of p38α MAPK and PDE4 is able to synergistically attenuate the excessive anti-inflammatory response.

背景与目标： : p38丝裂原活化蛋白激酶 (MAPK) 抑制剂的抗炎潜力被巧合地扩展为对p38α MAPK和磷酸二酯酶4 (PDE4) 的双重抑制，并且两种炎症相关酶的阻断所产生的潜在益处被彻底研究。在对啮齿动物，狗和猴子施用1之后，在体外实验以及体外和体内临床前研究中相继评估了最有希望的化合物CBS-3595 (1)。所得数据清楚地表明有效抑制了肿瘤坏死因子 α 的释放。为了在向健康的人类志愿者施用1时再次确认动物研究的结果，进行了I期临床试验。除了有关1的药代动力学和药效学特征的进一步信息外，还证明了p38α MAPK和PDE4的双重抑制能够协同减弱过度的抗炎反应。

BACKGROUND & AIMS: BACKGROUND:We modified and reconstructed a high image quality portable non-mydriatic fundus camera and compared it with the tabletop fundus camera to evaluate the efficacy of the new camera in detecting retinal diseases. METHODS:We designed and built a novel portable handheld fundus camera with telemedicine system. The image quality of fundus cameras was compared to that of existing commercial tabletop cameras by taking photographs of 364 eyes from the 254 patients. In all 800 fundus images taken by two camera types, 400 images per camera, were graded with the four image clarity classifications. RESULTS:Using the portable fundus camera, 63% (252/400) images were graded as excellent overall quality, 20.5% (82/400) were good, 11.75% (47/400) were fair, and 4.75% (19/400) were inadequate. Using the tabletop fundus camera, 70.75% (283/400) images were graded as excellent overall quality, 20.4% (51/400) were good, 13.25% (53/400) were fair, and 3.25% (13/400) were inadequate. Common retinal diseases were easily identified from fundus images obtained from the portable fundus camera. CONCLUSION:The new type of non-mydriatic portable fundus camera was qualified to have professional quality of fundus images. The revolutionary screening camera provides a foundational platform which can potentially improve the accessibility of retinal screening programmes.

背景与目标：

BACKGROUND & AIMS: :Over an 8 year period, 170 patients with multiple sclerosis (MS) and 134 healthy controls were assessed at monthly intervals in order to ascertain environmental factors which might be important in producing exacerbation or progression of the illness, and to compare the frequency of common viral infections in the two groups. During cumulative periods designated "at risk" (2 weeks before the onset of infection until 5 weeks afterwards) annual exacerbation rates were almost 3-fold greater than those during periods not at risk. Approximately 9% of infections were temporally related to exacerbations, whereas 27% of exacerbations were related to infections. Frequency of common infections was approximately 20-50% less in MS patients than controls; it was progressively less in those with greater disability. Even in minimally disabled patients with similar potential for infectious contacts, the infection rate was significantly less than in controls, suggesting that MS patients could have superior immune defences against common viruses.

背景与目标： : 在8年的时间里，每月对170名多发性硬化症 (MS) 患者和134名健康对照者进行评估，以确定可能对疾病恶化或进展很重要的环境因素，并比较两组中常见病毒感染的频率。在指定为 “处于危险中” 的累积期间 (感染发作前2周至之后5周)，年恶化率几乎是无危险期间的3倍。大约9% 的感染在时间上与恶化有关，而27% 的恶化与感染有关。MS患者的常见感染频率比对照组低约20-50%; 残疾程度较高的患者逐渐减少。即使在具有类似感染接触潜力的最小残疾患者中，感染率也明显低于对照组，这表明MS患者可以对普通病毒具有出色的免疫防御能力。

BACKGROUND & AIMS: :The prevalence of renal diseases is rising and reaching 5-15% of the adult population. Renal damage is associated with disturbances of body homeostasis and the loss of equilibrium between exogenous and endogenous elements including drugs and metabolites. Studies indicate that renal diseases are influenced not only by environmental but also by genetic factors. In some cases the disease is caused by mutation in a single gene and at that time severity depends on the presence of one or two mutated alleles. In other cases, renal disease is associated with the presence of alteration within a gene or genes, but environmental factors are also necessary for the development of disease. Therefore, it seems that the analysis of genetic aspects should be a natural component of clinical and experimental studies. The goal of personalized medicine is to determine the right drug, for the right patient, at the right time. Whole-genome examinations may help to change the approach to the disease and the patient resulting in the creation of "personalized medicine" with new diagnostic and treatment strategies designed on the basis of genetic background of each individual. The identification of high-risk patients in pharmacogenomics analyses will help to avoid many unwarranted side effects while optimizing treatment efficacy for individual patients. Personalized therapies for kidney diseases are still at the preliminary stage mainly due to high costs of such analyses and the complex nature of human genome. This review will focus on several areas of interest: renal disease pathogenesis, diagnosis, treatment, rate of progression and the prediction of prognosis.

背景与目标： : 肾脏疾病的患病率正在上升，并达到成年人口的5-15%。肾脏损害与机体稳态紊乱以及外源性和内源性元素 (包括药物和代谢物) 之间平衡的丧失有关。研究表明，肾脏疾病不仅受环境影响，还受遗传因素影响。在某些情况下，该疾病是由单个基因突变引起的，当时的严重程度取决于一个或两个突变等位基因的存在。在其他情况下，肾脏疾病与一个或多个基因内的改变有关，但环境因素也是疾病发展所必需的。因此，似乎遗传方面的分析应该是临床和实验研究的自然组成部分。个性化医疗的目标是在正确的时间为正确的患者确定正确的药物。全基因组检查可能有助于改变疾病和患者的治疗方法，从而创建具有基于每个个体遗传背景设计的新诊断和治疗策略的 “个性化医学”。在药物基因组学分析中识别高危患者将有助于避免许多不必要的副作用，同时优化单个患者的治疗效果。肾脏疾病的个性化治疗仍处于初步阶段，这主要是由于此类分析的高昂成本和人类基因组的复杂性。这篇综述将集中在几个感兴趣的领域: 肾脏疾病的发病机制，诊断，治疗，进展率和预后预测。

BACKGROUND & AIMS: OBJECTIVE:Genetic susceptibility to inflammatory bowel disease is well recognized. There is also increasing evidence for the activation of the mucosal immune system and the production of inflammatory cytokines, i.e., interleukin (IL)-1ra and IL-1beta in the inflammatory bowel disease. The aim of this study was to analyze the IL-1beta and IL-1ra gene polymorphism and linkage disequilibrium coefficient between the different alleles of these genes in patients with Crohn's disease (CD) or ulcerative colitis (UC), according to the severity of the disease.

METHODS:Two hundred twenty-eight inflammatory bowel disease patients (87 UC and 141 CD) were included in this study and compared with 113 unrelated controls. The IL-1beta and IL-1ra gene polymorphism was studied after specific amplification of variable regions by PCR. A penta-allelic polymorphism, corresponding to a VNTR region located in intron 2 of the IL-1ra gene, was analyzed, whereas bi-allelic RFLPs displayed by two restriction enzymes (TaqI and AvaI) at position -511 of the IL-1beta gene were analyzed.

RESULTS:There was no significant difference of genotype distribution between controls and CD or UC patients. However, surgically treated UC patients were characterized by a higher frequency of genotype IL-1ra 1-2 (39 vs 16%, pc < 0.01) compared with nonoperated UC patients. Moreover, nonoperated UC patients displayed a lower frequency of IL-1ra allele 2 than surgically treated UC patients (14 vs 34%, pc < 0.002) or controls (14 vs 30%, pc < 0.005). Furthermore, simultaneous analysis of the IL-1beta and IL-1ra genes that are located in the same region of chromosome 2 revealed that CD patients carrying the IL-1beta allele 2 were more often noncarriers of IL-1ra allele 2 (p < 0.005). Moreover, UC and CD patients were, characterized by a lower frequency of the association of IL-1ra allele 2 and IL-1beta allele 2 compared with controls (8.3 vs 20.3% and 10.6 vs 20.3%, p < 0.03).

CONCLUSIONS:IL-1ra and IL-1beta gene polymorphism analysis from a clinical standpoint might help in defining UC prognosis. However, functional studies at both the circulating and mucosal level with stratification on allele associations, especially IL-1ra allele 2-IL-1beta allele 2 subgroups must be realized before therapeutic implications.

背景与目标： 目的 : 炎症性肠病的遗传易感性已广为人知。也有越来越多的证据表明粘膜免疫系统的激活和炎性细胞因子的产生，即炎症性肠病中的白介素 (IL)-1ra和IL-1beta。本研究的目的是分析克罗恩病 (CD) 或溃疡性结肠炎 (UC) 患者中这些基因的不同等位基因之间的IL-1beta和IL-1ra基因多态性以及连锁不平衡系数。根据疾病的严重程度。
方法 : 本研究纳入了28例炎症性肠病患者 (87 UC和141 CD)，并与113例无关的对照进行了比较。通过PCR对可变区进行特异性扩增后，研究了IL-1beta和IL-1ra基因多态性。分析了五等位基因多态性，对应于位于IL-1ra基因内含子2中的VNTR区域，而分析了IL-1beta基因511位的两种限制酶 (TaqI和AvaI) 显示的双等位基因rflp。
结果 : 基因型分布在对照组和CD或UC患者之间没有显着差异。然而，与非手术UC患者相比，手术治疗的UC患者的特征是基因型IL-1ra 1-2的频率更高 (39 vs 16%，pc <0.01)。此外，与手术治疗的UC患者 (14 vs 34%，pc <0.002) 或对照 (14 vs 30%，pc <0.005) 相比，非手术UC患者显示出较低的IL-1ra等位基因2频率。此外，对位于2号染色体相同区域的IL-1beta和IL-1ra基因的同时分析表明，携带IL-1beta等位基因2的CD患者更经常是IL-1ra等位基因2的非携带者 (p <0.005)。此外，UC和CD患者的特征是与对照组相比，IL-1ra等位基因2和IL-1beta等位基因2的关联频率较低 (8.3 vs 20.3% 和10.6 vs 20.3%，p <0.03)。
结论 : 从临床角度来看，IL-1ra和IL-1beta基因多态性分析可能有助于确定UC预后。但是，必须在循环和粘膜水平上进行功能研究，并对等位基因关联进行分层，尤其是IL-1ra等位基因2-IL-1beta等位基因2亚组进行分层，然后才能产生治疗意义。

BACKGROUND & AIMS: :We investigated the genetic pathway in Arabidopsis thaliana targeted during infection by cucumber mosaic virus (CMV) 2b protein, known to suppress non-cell-autonomous transgene silencing and salicylic acid (SA)-mediated virus resistance. We show that 2b expressed from the CMV genome drastically reduced the accumulation of 21-, 22-, and 24-nucleotide classes of viral small interfering RNAs (siRNAs) produced by Dicer-like4 (DCL4), DCL2, and DCL3, respectively. The defect of a CMV 2b-deletion mutant (CMV-Delta2b) in plant infection was efficiently rescued in Arabidopsis mutants producing neither 21- nor 22-nucleotide viral siRNAs. Since genetic analysis further identifies a unique antiviral role for DCL3 upstream of DCL4, our data indicate that inhibition of the accumulation of distinct viral siRNAs plays a key role in 2b suppression of antiviral silencing. Strikingly, disease symptoms caused by CMV-Delta2b in Arabidopsis mutants defective in antiviral silencing were as severe as those caused by CMV, demonstrating an indirect role for the silencing suppressor activity in virus virulence. We found that production of CMV siRNAs without 2b interference depended largely on RNA-dependent RNA polymerase 1 (RDR1) inducible by SA. Given the known role of RDR6-dependent transgene siRNAs in non-cell-autonomous silencing, our results suggest a model in which 2b inhibits the production of RDR1-dependent viral siRNAs that confer SA-dependent virus resistance by directing non-cell-autonomous antiviral silencing.

背景与目标： : 我们研究了在黄瓜花叶病毒 (CMV) 2b蛋白感染期间针对拟南芥的遗传途径，该蛋白已知可抑制非细胞自主转基因沉默和水杨酸 (SA) 介导的病毒抗性。我们显示，从CMV基因组表达的2b分别大大减少了由Dicer-like4 (DCL4)，DCL2和DCL3产生的21、22和24核苷酸类病毒小干扰rna (sirna) 的积累。在既不产生21个或22个核苷酸的病毒sirna的拟南芥突变体中，有效地挽救了植物感染中CMV 2b缺失突变体 (CMV-Delta2b) 的缺陷。由于遗传分析进一步确定了DCL4上游DCL3的独特抗病毒作用，因此我们的数据表明，抑制不同病毒sirna的积累在2b抑制抗病毒沉默中起着关键作用。令人惊讶的是，在抗病毒沉默中缺陷的拟南芥突变体中由CMV-Delta2b引起的疾病症状与由CMV引起的症状一样严重，表明沉默抑制活性在病毒毒力中的间接作用。我们发现，没有2b干扰的CMV sirna的产生在很大程度上取决于SA诱导的RNA依赖性RNA聚合酶1 (RDR1)。鉴于RDR6-dependent转基因sirna在非细胞自主沉默中的已知作用，我们的结果提出了一种模型，其中2b通过指导非细胞自主抗病毒沉默抑制赋予SA依赖性病毒抗性的RDR1-dependent病毒sirna的产生。

BACKGROUND & AIMS: :A series of cell lines, which differed in their expression of class I (H-2K) or II (I-A) major histocompatibility complex (MHC) antigens, was derived from a line of C3H/He (H-2k) mouse embryo fibroblasts transformed by the v-Ki-ras oncogene. These were prepared by fluorescence-activated cell sorting of cells stained for these antigens either without interferon (IFN) treatment or after induction of antigen expression by either IFN-alpha beta or IFN-gamma, selecting for low or high staining. Cells selected for low (undetectable) constitutive H-2Kk expression were still strongly inducible by either IFN; cells selected for high constitutive expression were induced by IFN to express still higher levels. In all cell lines induction of H-2Kk with one IFN type was paralleled by induction with the other. Expression of H-2Kk appeared largely independent of H-2Dk; in lines which were selected for low H-2Kk expression (constitutive or induced), H-2Dk expression was not much reduced, and lines selected for high H-2Kk expression showed only modest augmentation of H-2Dk. Varying inducibility of I-Ak by IFN-gamma was not closely paralleled by H-2K inducibility by either IFN-alpha beta or -gamma, with again only weak correlation of high and low expression of H2-Kk and I-Ak. On the other hand, expression of I-Ak seemed to be correlated with I-Ek. None of these variable effects could be attributed to differing sensitivity to IFN-alpha beta or -gamma since all the lines showed about the same sensitivity to the anti-viral effects of IFN.

背景与目标： : 一系列细胞系，其I类 (H-2K) 或II类 (i-a) 主要组织相容性复合物 (MHC) 抗原的表达不同，源自由v-Ki-ras癌基因转化的C3H/He (H-2k) 小鼠胚胎成纤维细胞。这些是通过荧光激活的细胞分选针对这些抗原染色的细胞而制备的，无需干扰素 (IFN) 处理或在通过IFN-α β 或IFN-γ 诱导抗原表达后，选择低或高染色。被选择用于低 (不可检测) 组成型H-2Kk表达的细胞仍然被IFN强烈诱导; 被选择用于高组成型表达的细胞被IFN诱导以表达更高的水平。在所有细胞系中，具有一种IFN类型的H-2Kk的诱导与另一种类型的诱导平行。H-2Kk的表达似乎在很大程度上独立于H-2Dk; 在被选择用于低H-2Kk表达 (组成型或诱导型) 的品系中，H-2Dk表达没有减少太多，而被选择用于高H-2Kk表达的品系仅显示出适度的H-2Dk增加。IFN-γ 对I-Ak的诱导性变化与IFN-α β 或-γ 的H-2K诱导性并不紧密平行，H2-Kk和I-Ak的高表达和低表达也仅弱相关。另一方面，i-ak的表达似乎与i-ek相关。这些可变效应都不能归因于对IFN-alpha β 或-γ 的敏感性不同，因为所有品系对IFN的抗病毒效应均表现出相同的敏感性。