CCL22在人类免疫缺陷病毒感染中的作用

CCL22是CC型的趋化因子,其受体为CCR4.CCL22抑制巨噬细胞中R5人类免疫缺陷病毒1型的复制,其影响的不是病毒侵入或反转录等早期过程,而是作用于病毒侵入细胞后阶段.对CCL22独特功能的深入研究和CCR4这一病毒新共受体的发现将为人类免疫缺陷病毒的防治提供新的途径.     

γδ T细胞抗人类免疫缺陷病毒感染作用的研究进展

γδT细胞是表达γ和δ链的一群T细胞亚群,在抗人类免疫缺陷病毒(HIV)反应中发挥重要作用.本文主要从γδT细胞识别HIV、与HIV相互作用及其在临床方面的应用进行综述.     

庚型肝炎病毒抑制人类免疫缺陷病毒感染及其机制

庚型肝炎病毒(HGV/GBV-C)是10年前发现的单正链RNA病毒,属黄病毒科,病毒基因组RNA长约9.4kb),含1个开放读码框架,编码2 900左右的氨基酸.     

干扰素刺激基因15在人类免疫缺陷病毒感染中作用的研究进展

随着有效的联合抗反转录病毒疗法(combination antiretroviral therapy,cART)的普及,人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者的生存期逐步延长。这一过程中,HIV感染者自身免疫反应对免疫系统功能的恢复也发挥了至关重要的作用。HIV感染激活干扰素信号通路,诱导干扰素刺激基因(interferon-stimulated gene,ISG)上调表达,从而发挥抗病毒作用。其中,类泛素蛋白ISG15在HIV感染者中显著上调,通过ISG化抑制HIV颗粒的出芽和释放;而HIV的非结构蛋白则通过干扰ISG化过程或结合干扰素信号通路关键分子,逆转ISG15对病毒的抑制作用。本文从ISG15的生物学特性、在不同细胞亚群中的表达、抗病毒功能及病毒逃逸机制等方面进行综述,为进一步解析ISG15在HIV感染中扮演的角色、探索如何获得以抗HIV感染宿主因子为契机的治疗策略提供了思路。     

microRNA与病毒感染

microRNA是一类新近发现的由20-23个核苷酸构成的非编码RNA分子,它在生命进程中起着重要作用.病毒的复制和繁殖依赖于宿主细胞,而且对细胞环境的变化敏感.研究表明宿主和病毒都可以编码microRNA,病毒可通过小RNA介导的干扰作用影响宿主细胞,也能利用自身的"独特战略"改变宿主细胞从而满足自己生存的需求,所以,宿主与病毒间存在microRNA-mRNA相互作用的机制.尽管时microRNA与病毒感染的关系研究时间不长,但目前的研究结果为我们理解病毒和宿主之间的相互作用提供了一条途径,并为寻找病毒感染的生物标志物和治疗方法提供了新的思路.     

人类免疫缺陷病毒感染与特异性细胞毒性T淋巴细胞反应

特异性细胞毒性T淋巴细胞是一种能直接杀伤病毒及抗细胞内感染的效应细胞,大多数细胞毒性T淋巴细胞为CD8细胞,其反应是控制人类免疫缺陷病毒感染的重要免疫反应,但细胞毒性T淋巴细胞不能完全清除人类免疫缺陷病毒,这与病毒在体内的高度变异及病毒攻击人体免疫系统导致免疫功能改变有关。     

不同人类免疫缺陷病毒感染途径群体中戊型肝炎病毒的流行情况

本研究旨在了解不同人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染途径群体中戊型肝炎病毒(hepatitis E virus,HEV)抗体情况,探讨HEV疫苗接种的必要性。采集HIV感染者的血清或血浆,利用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测HEV IgG抗体、IgM抗体及抗原,荧光定量聚合酶链反应(polymerase chain reaction,PCR)检测HEV核酸,Roche高纯化HIV-1核酸定量检测试剂盒(PCR荧光法)检测HIV感染者的HIV载量。比较分析不同HIV感染途径群体中HEV流行率的差别。结果显示,HIV感染者中HEV IgG抗体的阳性率为37.4%,静脉吸毒、成分献血和传播途径不明HIV感染群体的HEV IgG抗体阳性率分别为49.3%、39.5%和30.4%。HEV核酸荧光PCR检测结果均为阴性。3种HIV感染群体之间HEV IgG抗体阳性率差异无统计学意义(χ~2=2.978,P0.05)。HEV IgG阳性与阴性感染者之间HIV载量差异无统计学意义(P0.05)。结果提示,为保护HIV感染者免受HEV感染,应考虑接种HEV疫苗。     

北京地区部分人类免疫缺陷病毒基因型分析

我国于1985年发现第1例AIDS患者，据估计到2001年底我国艾滋病病毒(Human immunodeficiency viruses，HrV)感染者和患者累计数已达84万人，而且我国艾滋病的传播呈快速增长的态势，2001年报告艾滋病病毒感染数较上年增长了58％。HIV主要通过静脉吸毒、输血或使用血液制品以及不良性行     

siRNA, miRNA and HIV: promises and challenges

Small interfering RNA (siRNA) and microRNA (miRNA) are small RNAs of 18-25 nucleotides (nt) in length that play important roles in regulating gene expression. They are incorporated into an RNA-induced silencing complex (RISC) and serve as guides for silencing their corresponding target mRNAs based on complementary base-pairing.The promise of gene silencing has led many researchers to consider siRNA as an anti-viral tool. However, in long-term settings, many viruses appear to escape from this therapeutical strategy. An example of this may be seen in the case of human immunodeficiency virus type-1 (HIV-1) which is able to evade RNA silencing by either mutating the siRNAtargeted sequence or by encoding for a partial suppressor of RNAi (RNA interference). On the other hand, because miRNA targeting does not require absolute complementarity of base-pairing, mutational escape by viruses from miRNAspecified silencing may be more difficult to achieve. In this review, we discuss stratagems used by various viruses to avoid the cells‘ antiviral si/mi-RNA defenses and notions of how viruses might control and regulate host cell genes by encoding viral miRNAs (vmiRNAs).     

siRNA, miRNA and HIV: promises and challenges

INTRODUCTION The recent discovery of small interfering RNA (siRNA) revealed an important role for small RNAs in regulating gene expression. First described in plants, as “post- trancriptional gene silencing” (PTGS) [1], RNA interfer- ence (RNAi) is a nucleic-acid based immune defense against viruses, transgenes and transposons [2]. Triggered by double-stranded RNA (dsRNA), RNAi leads to the se- quence specific degradation of a target mRNA [3]. In eukaryotic cells, long dsRN…     

The use of miRNA microarrays for the analysis of cancer samples with global miRNA decrease

Recent studies have established that mutations or deletions in microRNA (miRNA) processing enzymes resulting in a global decrease of miRNA expression are frequent across cancers and can be associated with a poorer prognosis. While very popular in miRNA profiling studies, it remains unclear whether miRNA microarrays are suited or not to accurately detecting global miRNA decreases seen in cancers. In this work, we analyzed the miRNA profiles of samples with global miRNA decreases using Affymetrix miRNA microarrays following the inducible genetic deletion of Dicer1. Surprisingly, up to a third of deregulated miRNAs identified upon Dicer1 depletion were found to be up-regulated following standard robust multichip average (RMA) background correction and quantile normalization, indicative of normalization bias. Our comparisons of five preprocess steps performed at the probe level demonstrated that the use of cyclic loess relying on non-miRNA small RNAs present on the Affymetrix platform significantly improved specificity and sensitivity of detection of decreased miRNAs. These findings were validated in samples from patients with prostate cancer, where conjugation of robust normal-exponential background correction with cyclic loess normalization and array weights correctly identified the greatest number of decreased miRNAs, and the lowest amount of false-positive up-regulated miRNAs. These findings highlight the importance of miRNA microarray normalization for the detection of miRNAs that are truly differentially expressed and suggest that the use of cyclic loess based on non-miRNA small RNAs can help to improve the sensitivity and specificity of miRNA profiling in cancer samples with global miRNA decrease.     

Manipulating the Interferon Signaling Pathway: Implications for HIV Infection

During human immunodeficiency virus(HIV) infection, type I interferon(IFN-I) signaling induces an antiviral state that includes the production of restriction factors that inhibit virus replication, thereby limiting the infection. As seen in other viral infections, type I IFN can also increase systemic immune activation which, in HIV disease, is one of the strongest predictors of disease progression to acquired immune deficiency syndrome(AIDS) and non-AIDS morbidity and mortality.Moreover, IFN-I is associated with CD4 T cell depletion and attenuation of antigen-specific T cell responses. Therefore,therapeutic manipulation of IFN-I signaling to improve HIV disease outcome is a source of much interest and debate in thefield. Recent studies have highlighted the importance of timing(acute vs. chronic infection) and have suggested that specific targeting of type I IFNs and their subtypes may help harness the beneficial roles of the IFN-I system while avoiding its deleterious activities.     

siRNA, miRNA and HIV： promises and challenges

Small interfering RNA （siRNA） and microRNA （miRNA） are small RNAs of 18-25 nucleotides （nt） in length that play important roles in regulating gene expression. They are incorporated into an RNA-induced silencing complex （RISC） and serve as guides for silencing their corresponding target mRNAs based on complementary base-pairing. The promise of gene silencing has led many researchers to consider siRNA as an anti-viral tool. However, in long-term settings, many viruses appear to escape from this therapeutical strategy. An example of this may be seen in the case of human immunodeficiency virus type-1 （HIV-1） which is able to evade RNA silencing by either mutating the siRNA-targeted sequence or by encoding for a partial suppressor of RNAi （RNA interference）. On the other hand, because miRNA targeting does not require absolute complementarity of base-pairing, mutational escape by viruses from miRNA-specified silencing may be more difficult to achieve. In this review, we discuss stratagems used by various viruses to avoid the cells＇ antiviral si/mi-RNA defenses and notions of how viruses might control and regulate host cell genes by encoding viral miRNAs （vmiRNAs）.     

HIV Rev-isited

The human immunodeficiency virus type 1 (HIV-1) proteome is expressed from alternatively spliced and unspliced genomic RNAs. However, HIV-1 RNAs that are not fully spliced are perceived by the host machinery as defective and are retained in the nucleus. During late infection, HIV-1 bypasses this regulatory mechanism by expression of the Rev protein from a fully spliced mRNA. Once imported into the nucleus, Rev mediates the export of unprocessed HIV-1 RNAs to the cytoplasm, leading to the production of the viral progeny. While regarded as a canonical RNA export factor, Rev has also been linked to HIV-1 RNA translation, stabilization, splicing and packaging. However, Rev''s functions beyond RNA export have remained poorly understood. Here, we revisit this paradigmatic protein, reviewing recent data investigating its structure and function. We conclude by asking: what remains unknown about this enigmatic viral protein?     

细胞间粘附分子5（ICAM-5）在HIV相关神经损伤中的保护性作用

为探究细胞间粘附分子5 (intercellular adhesion molecule 5,ICAM-5)在HIV相关神经认知损伤中的作用,用ELISA法测定HIV感染者脑脊液样本和体外动物神经细胞培养体系中可溶性细胞间粘附分子5(ICAM-5s)的含量|蛋白印迹法检测ICAM-5蛋白表达|免疫荧光法观察神经细胞形态学变化|用CytoTox 96非放射性细胞毒性实验检测神经细胞死亡率.抗ICAM-5单克隆抗体Cy3标记的免疫荧光染色结果显示,ICAM-5可在神经元细胞的胞体和突起表达,且经HIV神经毒性蛋白gp120 500pmol/L处理的神经细胞平均突起长度显著小于无gp120处理的对照组|体外神经细胞培养体系中,gp120+基质金属蛋白酶3（MMP3）实验组的ICAM-5s含量显著高于gp120组,且前者神经元细胞的死亡率高于后者|在 HIV感染者中,HIV相关神经认知障碍（HIV associated neurocognitive disorder,HAND）患者脑脊液中ICAM 5s的水平显著高于认知功能正常的患者.结果表明,ICAM-5可能具有标记神经细胞突起的潜能,但其确切性有待进一步实验验证|ICAM-5与HIV相关神经认知功能损伤相关,具有潜在的神经元细胞保护作用.     

Mechanistic effects of kijimicin on inhibition of human immunodeficiency virus replication

Kijimicin represents an important type of ionophore compound. In veterinary medicine, it is becoming important as anticoccidiostatic agent and feed supplement. We examined Kijimicin for its HIV inhibitory activity. The compound exhibited concentration-dependent inhibition of HIV replication in primary infected cultures of human T-lymphoblastoid H9 cells. Substantial inhibition of viral replication was observed at concentrations of Kijimicin that showed little cytotoxicity. The ratio of IC₅₀ values for the MTT to RT assays was 40. Anti HIV activity was also observed in cultures of monocytic lineage U937 cells chronically infected with HIV. Moreover, in attempting to define the inhibitory mechanism of Kijimicin, we investigated its effect on each step of HIV replication. The infectivity of progeny viral particles was reduced by Kijimicin treatment. This decrease may be due to incompletely glycosylated forms of gp120.