TRIM21的抗病毒作用研究进展

TRIM(tripartite motif)家族因具有相似的N端结构又被称为RBCC家族,其成员在诸多与固有免疫相关的生物学过程中发挥重要作用.近年来的研究发现,TRIM家族参与宿主的胞内抗病毒作用,其中一些TRIM家族蛋白被认为是病毒的限制因子.最近,TRIM21作为E3泛素连接酶的抗病毒作用相继被报道,其可通过抗体依赖的细胞内抗病毒作用(antibody dependent intracellular neutralization,ADIN)及参与固有免疫通路发挥抗病毒作用,现就TRIM21的结构、表达分布、抗病毒作用及其机制的研究进展进行总结和综述.     

树突状细胞在抗病毒免疫及病毒性肝炎中的作用

树突状细胞是目前发现的功能最强的专职抗原递呈细胞，在免疫反应中起着举足轻重的作用。因此备受重视，其诱导的强烈的CTL反应在病毒性肝炎基因治疗中具有很好的应用前景。     

树突状细胞在抗病毒免疫及病毒性肝炎中的作用

树突状细胞是目前发现的功能最强的专职抗原递呈细胞 ,在免疫反应中起着举足轻重的作用 ,因此备受重视 ,其诱导的强烈的CTL反应在病毒性肝炎基因治疗中具有很好的应用前景。     

028 树突状细胞在抗病毒免疫及病毒性肝炎中的作用

树突状细胞是目前发现的功能最强的专职抗原递呈细胞,在免疫反应中起着举足轻重的作用,因此备受重视,其诱导的强烈的CTL反应在病毒性肝炎基因治疗中具有很好的应用前景.     

病毒免疫逃逸机制研究进展

在宿主和病毒的长期共同进化过程中,病毒发展了各种免疫逃逸机制以逃避宿主的免疫应答.这些免疫逃逸机制可大致分为三类(1)逃避体液免疫系统的识别;(2)抑制细胞免疫应答;(3)干扰免疫效应功能.而且,一些病毒还可通过与免疫系统隔离而逃避免疫应答.     

TRIM21胞内免疫功能与治疗应用

三基序蛋白21(tripartite -motif protein 21,TRIM21)是一种存在于细胞胞质内的泛素连接酶,也是一类胞内抗体受体或者感应器,成为抵御病毒入侵的固有免疫防线。对于在细胞外已经逃逸了中和抗体作用,并被非中和抗体吸附而通过细胞膜侵入细胞内的病毒,TRIM21可以通过与病毒-抗体复合物中的抗体F...     

病毒免疫逃逸机制研究进展

在宿主和病毒的长期共同进化过程中,病毒发展了各种免疫逃逸机制以逃避宿主的免疫应答.这些免疫逃逸机制可大致分为三类：（1）逃避体液免疫系统的识别;（2）抑制细胞免疫应答;（3）干扰免疫效应功能.而且,一些病毒还可通过与免疫系统隔离而逃避免疫应答.     

TRIM家族在宫颈癌中的研究进展

宫颈癌是女性中常见恶性肿瘤之一,病死率较高,全球死亡女性超过88％发生在发展中国家,其中以宫颈鳞癌最为常见.三方基序蛋白(tripartite motif-containing protein,TRIM)家族大多数具有E3泛素连接酶活性,且与多种生理过程有关,包括细胞增殖、DNA修复、信号转导和转录.近年大量研究发现TRIM家族通过多种通路参与宫颈癌的发生和发展.     

泛素E3连接酶TRIM10在心肌细胞肥大中的作用

目的:探讨泛素E3连接酶TRIM10在心肌细胞肥大中的作用及分子机制。方法:培养原代的大鼠乳鼠心肌细胞,siRNA-TRIM10与siRNA对照(siRNA-control)或过表达腺病毒Ad-TRIM10与空载对照Ad-GFP转染细胞24 h,然后用苯肾上腺素(phenylephrine,PE)处理细胞24 h。Western blot检测TRIM10、AKT和ERK1/2的蛋白水平;免疫荧光染色观察心肌细胞的大小;实时荧光定量PCR检测心房钠尿肽(ANP)和脑钠尿肽(BNP)的mRNA的表达水平。结果:与对照组相比,PE处理明显上调心肌细胞中TRIM10蛋白的表达水平。siRNA-TRIM10敲低内源性TRIM10表达后明显减小PE诱导的心肌细胞体积,抑制ANP和BNP的mRNA的表达以及降低AKT和ERK1/2的磷酸化水平;而过表达TRIM10则呈现出与siRNA-TRIM10完全相反的结果。结论:TRIM10可调节心肌细胞肥大,其作用可能与AKT和ERK信号相关。     

TRIM22稳定过表达细胞系的构建及其抗流感病毒的功能

目的构建稳定表达TRIM22的HEK293T细胞系HEK293T-TRIM22,观察TRIM22蛋白在该细胞内的表达及对流感病毒复制的影响并初步探究其抑制机制。方法扩增TRIM22基因并与反转录病毒载体进行体外重组连接,经菌液PCR、测序确认后与反转录病毒骨架载体共转染进HEK293T细胞进行包装病毒。用包装的反转录病毒感染HEK293T细胞,感染24 h后用嘌呤霉素筛选稳定过表达TRIM22的细胞,筛选48 h后用Western blot检测TRIM22表达水平;用IAV-LUC病毒检测稳定过表达TRIM22的HEK293T对流感病毒的抑制作用;再用双分子荧光互补实验(Bi LC)检测与TRIM22相互作用的流感蛋白。结果经测序确认目的基因TRIM22成功克隆到载体p QC-XIP中。包装反转录病毒并感染HEK293T细胞,经过嘌呤霉素筛选后,稳定过表达TRIM22的HEK293T细胞中TRIM22的蛋白表达水平升高(P0.05)。在稳定过表达TRIM22的细胞内流感病毒复制减弱(P0.05)。Bi LC检测TRIM22与流感蛋白NP有相互作用。结论稳定过表达TRIM22的HEK293T细胞系构建成功,TRIM22与NP有相互作用并且抑制流感病毒复制。     

Comparison of anti-viral activity of rhesus monkey and cynomolgus monkey TRIM5alphas against human immunodeficiency virus type 2 infection

Human immunodeficiency virus type 2 (HIV-2) strains vary widely in their ability to grow in Old World monkey (OWM) cells. We previously evaluated several HIV-2 isolates for their sensitivity to cynomolgus monkey (CM) TRIM5alpha, an anti-HIV factor in OWM cells, and found that viruses carrying proline at the 120th position of the capsid protein were sensitive to CM TRIM5alpha, whereas those with either alanine or glutamine were resistant. In the study presented here, we tested these HIV-2 isolates for their sensitivity to rhesus monkey (Rh) TRIM5alpha and found that both CM TRIM5alpha-sensitive and -resistant viruses were restricted by Rh TRIM5alpha. The variable region 1 of the SPRY domain of Rh TRIM5alpha appeared to be the determinant of this difference. Furthermore, a mutagenesis study showed that three amino acid residues TFP at the 339th to 341st positions of Rh TRIM5alpha are important for restricting HIV-2 strains resistant to CM TRIM5alpha.     

免疫系统在青光眼发病机制中的作用

青光眼曾被认为是一种病因单纯疾病,近些年研究表明,是由多原因导致的视神经永久性损伤和视野丢失的一类疾病。而免疫系统在青光眼的视网膜视神经损害中所起的作用应该是双重的。一方面自身免疫机制引起视神经损伤可以由自身抗体直接导致,也可以间接模拟对敏感抗原的自身免疫反应所引起,另一方面,免疫系统监督和调节可以对应激作出反应,从而起到一定保护作用。了解免疫系统在青光眼发病机制中的作用对于预防及治疗青光眼有着重要的意义。     

Outsmarting the host: bacteria modulating the immune response

Pathogenic bacteria and their hosts have had a two-way conversation for millions of years. This interaction has led to many measure/counter-measure responses by the host and bacteria. The host immune response has developed many mechanisms to neutralize and remove pathogen bacteria. In turn pathogenic bacteria have developed mechanisms to alter and evade the host immune response. We will review some of the mechanisms utilized by bacteria to accomplish this goal. We will also examine the current state of understanding of Francisella tularensis mediated immune evasion.     

Functional analysis of the human cytomegalovirus immune evasion protein, pUS3(22kDa)

Human cytomegalovirus (HCMV) is an important opportunistic pathogen that infrequently causes disease in individuals with mature immune systems. The HCMV US3 gene encodes a 22-kDa protein that interferes with immune recognition of virally infected cells. The 22-kDa US3 protein binds to major histocompatibility complex (MHC) class I complexes, retaining them in the endoplasmic reticulum (ER), thereby decreasing the presentation of viral antigen to cytotoxic T cells. Our studies demonstrate that correct folding of the ER lumenal domain of the US3 protein is essential, but insufficient for interactions with MHC class I complexes. We demonstrate a requirement for the transmembrane domain of the 22-kDa US3 protein, confirming the results of others, and also show that the cytosolic carboxyl-terminal tail influences the function of the protein. Anchoring of the ER-lumenal immunoglobulin-like fold of the US3 protein to the membrane of the endoplasmic reticulum is critical for the binding and retention of MHC class I complexes.     

Inherent specificities in natural antibodies: a key to immune defense against pathogen invasion

Natural antibodies are produced at tightly regulated levels in the complete absence of external antigenic stimulation. They provide immediate, early and broad protection against pathogens, making them a crucial non-redundant component of the humoral immune system. These antibodies are produced mainly, if not exclusively, by a subset of long-lived, self-replenishing B cells termed B-1 cells. We argue here that the unique developmental pattern of these B-1 cells, which rests on positive selection by self antigens, ensures production of natural antibodies expressing evolutionarily important specificities that are required for the initial defense against invading pathogens. Positive selection for reactivity with self antigens could also result in the production of detrimental anti-self antibodies. However, B-1 cells have evolved a unique response pattern that minimizes the risk of autoimmunity. Although these cells respond rapidly and strongly to host-derived innate signals, such as cytokines, and to pathogen-encoded signals, such as lipopolysaccharide and phosphorylcholine, they respond very poorly to receptor-mediated activation. In addition, they rarely enter germinal centers and undergo affinity maturation. Thus, their potential for producing high-affinity antibodies with harmful anti-self specificity is highly restricted. The positive selection of B-1 cells occurs during the neonatal period, during which the long-lived self-renewing B-1 population is constituted. Many of these cells (B-1a) express CD5, although a smaller subset (B-1b) does not express this surface marker. Importantly, B-1a cells should not be confused with short-lived anergic B-2 cells, which originate in the bone marrow in adults and initiate CD5 expression and programmed cell death following self-antigen recognition. In summary, we argue here that the mechanisms that enable natural antibody production by B-1 cells reflect the humoral immune system, which has evolved in layers whose distinct developmental mechanisms generate complementary repertoires that collectively operate to maximize flexibility in responses to invading pathogens. B-2 cells, present in what may be the most highly evolved layer(s), express a repertoire that is explicitly selected against self recognition and directed towards the generation of high-affinity antibody response to external antigenic stimuli. B-1 cells, whose repertoire is selected by recognition of self antigen, belong to what may be earlier layer(s) and inherently maintain production of evolutionarily important antibody specificities that respond to pathogen-related, rather then antigen-specific signals.     

Complement and immune defense: From innate immunity to human diseases

The human organism is constantly exposed to microbes and infectious agents and consequently has developed a complex and highly efficient immune defense which is aimed to recognize and eliminate such infectious agents. The response of the human host to infectious agents forms a double edged sword of immunity. The immune system has to keep a tight balance between attack on foreign surfaces and protection of host surfaces. In its proper function the immune response is aimed to recognize, attack and eliminate invading infectious agents and this response is beneficial for the host. However when the activated immune response like the complement system is not properly controlled and deregulated, effector compounds can attack and damage self-surfaces and this results in disease. In addition pathogens which cause infections and disease protect themselves from the damaging and harmful host immune weapon and use specific immune escape strategies. The complement system forms the first defense line of innate immunity and aids in the elimination of microbes and modified self-cells. Defective regulation of this cascade type system results in infections and in pathology. This can result in diseases, like severe renal diseases hemolytic uremic syndrome (HUS) and dense deposit disease (DDD), in age related macular degeneration a common form of blindness and also in other forms of autoimmune diseases.