首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
Feldmann J  Schwartz O 《Viruses》2010,2(8):1666-1680
A relatively new aspect of HIV-1 biology is the ability of the virus to infect cells by direct cellular contacts across a specialized structure, the virological synapse. This process was recently described through live cell imaging. Together with the accumulated knowledge on cellular and molecular structures involved in cell-to-cell transmission of HIV-1, the visualization of the virological synapse in video-microscopy has brought exciting new hypotheses on its underlying mechanisms. This review will recapitulate current knowledge with a particular emphasis on the questions live microscopy has raised.  相似文献   

2.
The virological synapse (VS) is a tight adhesive junction between an HIV-infected cell and an uninfected target cell, across which virus can be efficiently transferred from cell to cell in the absence of cell-cell fusion. The VS has been postulated to resemble, in its morphology, the well-studied immunological synapse (IS). This review article discusses the structural similarities between IS and VS and the shared T cell receptor (TCR) signaling components that are found in the VS. However, the IS and the VS display distinct kinetics in disassembly and intracellular signaling events, possibly leading to different biological outcomes. Hence, HIV-1 exploits molecular components of IS and TCR signaling machinery to trigger unique changes in cellular morphology, migration, and activation that facilitate its transmission and cell-to-cell spread.  相似文献   

3.
HIV-1 infection is enhanced by cell–cell adhesions between infected and uninfected T cells called virological synapses (VS). VS are initiated by the interactions of cell-surface HIV-1 envelope glycoprotein (Env) and CD4 on target cells and act as sites of viral assembly and viral transfer between cells. To study the process that recruits and retains HIV-1 Env at the VS, a replication-competent HIV-1 clone carrying an Env-sfGFP fusion protein was designed to enable live tracking of Env within infected cells. Combined use of surface pulse-labeling of Env and fluorescence recovery after photobleaching (FRAP) studies, enabled the visualization of the targeted accumulation and sustained recycling of Env between endocytic compartments (EC) and the VS. We observed dynamic exchange of Env at the VS, while the viral structural protein, Gag, was largely immobile at the VS. The disparate exchange rates of Gag and Env at the synapse support that the trafficking and/or retention of a majority of Env towards the VS is not maintained by entrapment by a Gag lattice or immobilization by binding to CD4 on the target cell. A FRAP study of an Env endocytosis mutant showed that recycling is not required for accumulation at the VS, but is required for the rapid exchange of Env at the VS. We conclude that the mechanism of Env accumulation at the VS and incorporation into nascent particles involves continuous internalization and targeted secretion rather than irreversible interactions with the budding virus, but that this recycling is largely dispensable for VS formation and viral transfer across the VS.  相似文献   

4.
Human T-cell leukemia virus type 1 (HTLV-1) causes serious and intractable diseases in some carriers after infection. The elimination of infected cells is considered important to prevent this onset, but there are currently no means by which to accomplish this. We previously developed “virotherapy”, a therapeutic method that targets and kills HTLV-1-infected cells using a cytolytic recombinant vesicular stomatitis virus (rVSV). Infection with rVSV expressing an HTLV-1 primary receptor elicits therapeutic effects on HTLV-1-infected envelope protein (Env)-expressing cells in vitro and in vivo. Simian T-cell leukemia virus type 1 (STLV-1) is closely related genetically to HTLV-1, and STLV-1-infected Japanese macaques (JMs) are considered a useful HTLV-1 surrogate, non-human primate model in vivo. Here, we performed an in vitro drug evaluation of rVSVs against STLV-1 as a preclinical study. We generated novel rVSVs encoding the STLV-1 primary receptor, simian glucose transporter 1 (JM GLUT1), with or without an AcGFP reporter gene. Our data demonstrate that these rVSVs specifically and efficiently infected/eliminated the STLV-1 Env-expressing cells in vitro. These results indicate that rVSVs carrying the STLV-1 receptor could be an excellent candidate for unique anti-STLV-1 virotherapy; therefore, such antivirals can now be applied to STLV-1-infected JMs to determine their therapeutic usefulness in vivo.  相似文献   

5.
6.
Human T-lymphotropic virus type 1 (HTLV-1) is found in indigenous peoplesof the Pacific Islands and the Americas, whereas type 2 (HTLV-2) is widelydistributed among the indigenous peoples of the Americas, where it appears to be moreprevalent than HTLV-1, and in some tribes of Central Africa. HTLV-2 is consideredancestral in the Americas and is transmitted to the general population and injectiondrug users from the indigenous population. In the Americas, HTLV-1 has more than oneorigin, being brought by immigrants in the Paleolithic period through the BeringStrait, through slave trade during the colonial period, and through Japaneseimmigration from the early 20th century, whereas HTLV-2 was only broughtby immigrants through the Bering Strait. The endemicity of HTLV-2 among theindigenous people of Brazil makes the Brazilian Amazon the largest endemic area inthe world for its occurrence. A review of HTLV-1 in all Brazilian tribes supports theAfrican origin of HTLV-1 in Brazil. The risk of hyperendemicity in theseepidemiologically closed populations and transmission to other populations reinforcesthe importance of public health interventions for HTLV control, including therecognition of the infection among reportable diseases and events.  相似文献   

7.
Human T-cell leukemia virus type 1 (HTLV-1) is commonly accepted as the cause of adult T-cell leukemia and tropical spastic paraparesis/HTLV-1-associated myelopathy. Screening of blood donors for HTLV-1 and HTLV-2 was implemented in Taiwan in February 1996. From February 1996 to December 1998, we investigated the seroprevalence of HTLV-1 in all unpaid blood donors in Taiwan. Of 2,578,238 donors in all 6 blood centers, 1793 (0.06%) were seropositive for HTLV-1, and 605 (0.023%) were indeterminate for HTLV-1. Among these indeterminate donors, 359 (59.3%) were male. The most common HTLV-1-indeterminate pattern by Western blot in our study was GD21 alone (34.6%) followed by p24 alone (7.8%), p53 alone (6.5%), and gp46 + GD21 (6.0%). That GD21 pattern was found in 59.6% of indeterminate results in this study suggested that the majority of nonspecific enzyme immunoassay reactions were probably precipitated by viral envelop glycoprotein GD21.  相似文献   

8.
Jolly C 《Viruses》2010,2(6):1261-1278
Cell-to-cell spread of HIV-1 between CD4(+) T cells takes place at multimolecular structures called virological synapses. A defining feature of the virological synapse is polarization of viral assembly and budding at sites of T cell-T cell contact. Recent work is beginning to address how viral proteins are targeted to the virological synapse and the molecular mechanisms that regulate HIV-1 egress by cell-to-cell spread. This review discusses our current understanding of these processes and considers how T cell polarization during other forms of intercellular communication may provide insight into HIV-1 assembly and dissemination.  相似文献   

9.
10.
Human T-lymphotropic virus type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL). Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM) is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Sjögren’s Syndrome (SS). The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4+ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4+ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity.  相似文献   

11.
Malbec M  Roesch F  Schwartz O 《Viruses》2011,3(3):254-259
Retroviruses like HIV-1 and HTLV-1 can be transmitted efficiently by direct contact between infected and target cells. For HIV-1, various modes of cell-to-cell transfer have been reported, including virological synapses, polysynapses, filopodial bridges, and nanotube-like structures. So far, only synapses and biofilms have been described for HTLV-1 transmission. Recently, Van Prooyen et al. [1] identified an additional mode of HTLV-1 transmission through cellular conduits induced by the viral accessory protein p8.  相似文献   

12.
13.
Journo C  Mahieux R 《Viruses》2011,3(8):1374-1394
Innate immunity plays a critical role in the host response to a viral infection. The innate response has two main functions. First, it triggers effector mechanisms that restrict the infection. Second, it primes development of the adaptive response, which completes the elimination of the pathogen or of infected cells. In vivo, HTLV-1 infects T lymphocytes that participate in adaptive immunity but also monocytes and dendritic cells that are major players in innate immunity. Herein, we will review the interplay between HTLV-1 and innate immunity. Particular emphasis is put on HTLV-1-induced alteration of type-I interferon (IFN-I) function. In vitro, the viral Tax protein plays a significant role in the alteration of IFN synthesis and signaling. Despite this, IFN-I/AZT treatment of Adult T-cell Leukemia/Lymphoma (ATLL) patients leads to complete remission. We will discuss a model in which exogenous IFN-I could act both on the microenvironment of the T-cells to protect them from infection, and also on infected cells when combined with other drugs that lead to Tax down-regulation/degradation.  相似文献   

14.
T cells infected with human T-cell leukemia virus type 1 (HTLV-1) acquire various abnormalities during a long latent period and transform into highly malignant adult T-cell leukemia-lymphoma (ATL) cells. This can be described as “clonal evolution”, in which a single clone evolves into ATL cells after overcoming various selective pressures in the body of the infected individuals. Many studies have shown that the genome and epigenome contain a variety of abnormalities, which are reflected in gene expression patterns and define the characteristics of the disease. The latest research findings suggest that epigenomic disorders are thought to begin forming early in infection and evolve into ATL through further changes and accentuation as they progress. Genomic abnormalities profoundly affect clonal dominance and tumor cell characteristics in later events. ATL harbors both genomic and epigenomic abnormalities, and an accurate understanding of these can be expected to provide therapeutic opportunities.  相似文献   

15.
HIV, HTLV-1/-2, and HCV share routes of transmission, and such virus co-infections could account for worse outcomes of associated diseases. Measuring cytokines/chemokines, CD4 and CD8 T cells, and HIV viral load (VL) in HIV single-infected and co-infected individuals has prognostic value. We analyzed such biomarkers in 129 blood samples of HIV-infected individuals matched for age and sex and divided into six groups (G1 (69 HIV); G2 (9 HIV/HTLV-1); G3 (6 HIV/HTLV-2); G4 (11 HIV/HCV); G5 (19 HIV/HCV/HTLV-1); and G6 (15 HIV/HCV/HTLV-2)). Eight cytokines/chemokines from fifteen analytes could be compared. The highest levels of Th1 and pro-inflammatory cytokines were detected in G2 (IFN-γ) and G6 (IL-6 and IL1-β) and of chemokines in G1 (MIG, IP10, RANTES), G4 (MCP1), and G6 (MIP1-β). The highest CD4 cells number and the lowest HIV VL were identified in G3 and the opposite results in G2. Positive correlations between CD4 and CD8 cells counts and IL-6 levels were detected in G2 and G5 and of HIV VL and RANTES in G4. Negative correlations were detected between CD8 and IFN-γ in G4 and HIV VL and RANTES in G6. Despite the small number of the cohort analyzed, and although the cross-sectional study design does not allow firm conclusions, the homogeneity of the characteristics of HIV/HTLV-co-infected individuals regarding age, time and route of HIV acquisition, and criteria for introducing ART enable us to suggest a negative impact of HTLV-1 and a possible protective role of HTLV-2 in HIV infection progression in such patients.  相似文献   

16.
HTLV-1 uveitis (HU) is the third clinical entity to be designated as an HTLV-1-associated disease. Although HU is considered to be the second-most frequent HTLV-1-associated disease in Japan, information on HU is limited compared to that on adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Recent studies have addressed several long-standing uncertainties about HU. HTLV-1-related diseases are known to be caused mainly through vertical transmission (mother-to-child transmission), but emerging HTLV-1 infection by horizontal transmission (such as sexual transmission) has become a major problem in metropolitan areas, such as Tokyo, Japan. Investigation in Tokyo showed that horizontal transmission of HTLV-1 was responsible for HU with severe and persistent ocular inflammation. The development of ATL and HAM is known to be related to a high provirus load and hence involves a long latency period. On the other hand, factors contributing to the development of HU are poorly understood. Recent investigations revealed that severe HU occurs against a background of Graves’ disease despite a low provirus load and short latency period. This review highlights the recent knowledge on HU and provides an update on the topic of HU in consideration of a recent nationwide survey.  相似文献   

17.
The human retrovirus human T-cell leukemia virus type I (HTLV-1) infects human T cells by vertical transmission from mother to child through breast milk or horizontal transmission through blood transfusion or sexual contact. Approximately 5% of infected individuals develop adult T-cell leukemia/lymphoma (ATL) with a poor prognosis, while 95% of infected individuals remain asymptomatic for the rest of their lives, during which time the infected cells maintain a stable immortalized latent state in the body. It is not known why such a long latent state is maintained. We hypothesize that the role of functional proteins of HTLV-1 during early infection influences the phenotype of infected cells in latency. In eukaryotic cells, a mRNA quality control mechanism called nonsense-mediated mRNA decay (NMD) functions not only to eliminate abnormal mRNAs with nonsense codons but also to target virus-derived RNAs. We have reported that HTLV-1 genomic RNA is a potential target of NMD, and that Rex suppresses NMD and stabilizes viral RNA against it. In this study, we aimed to elucidate the molecular mechanism of NMD suppression by Rex using various Rex mutant proteins. We found that region X (aa20–57) of Rex, the function of which has not been clarified, is required for NMD repression. We showed that Rex binds to Upf1, which is the host key regulator to detect abnormal mRNA and initiate NMD, through this region. Rex also interacts with SMG5 and SMG7, which play essential roles for the completion of the NMD pathway. Moreover, Rex selectively binds to Upf3B, which is involved in the normal NMD complex, and replaces it with a less active form, Upf3A, to reduce NMD activity. These results revealed that Rex invades the NMD cascade from its initiation to completion and suppresses host NMD activity to protect the viral genomic mRNA.  相似文献   

18.
Kannian P  Green PL 《Viruses》2010,2(9):2037-2077
Human T lymphotropic viruses (HTLVs) are complex deltaretroviruses that do not contain a proto-oncogene in their genome, yet are capable of transforming primary T lymphocytes both in vitro and in vivo. There are four known strains of HTLV including HTLV type 1 (HTLV-1), HTLV-2, HTLV-3 and HTLV-4. HTLV-1 is primarily associated with adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-2 is rarely pathogenic and is sporadically associated with neurological disorders. There have been no diseases associated with HTLV-3 or HTLV-4 to date. Due to the difference in the disease manifestation between HTLV-1 and HTLV-2, a clear understanding of their individual pathobiologies and the role of various viral proteins in transformation should provide insights into better prognosis and prevention strategies. In this review, we aim to summarize the data accumulated so far in the transformation and pathogenesis of HTLV-1, focusing on the viral Tax and HBZ and citing appropriate comparisons to HTLV-2.  相似文献   

19.
Human T-cell leukemia virus type 1 (HTLV-1), hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are prevalent worldwide, and share similar means of transmission. These infections may influence each other in evolution and outcome, including cancer or immunodeficiency. Many studies have reported the influence of genetic markers on the host immune response against different persistent viral infections, such as HTLV-1 infection, pointing to the importance of the individual genetic background on their outcomes. However, despite recent advances on the knowledge of the pathogenesis of HTLV-1 infection, gaps in the understanding of the role of the individual genetic background on the progress to disease clinically manifested still remain. In this scenario, much less is known regarding the influence of genetic factors in the context of dual or triple infections or their influence on the underlying mechanisms that lead to outcomes that differ from those observed in monoinfection. This review describes the main factors involved in the virus–host balance, especially for some particular human leukocyte antigen (HLA) haplotypes, and other important genetic markers in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other persistent viruses, such as HIV and HCV.  相似文献   

20.
Eosinophils, immunoglobulin (Ig)E and cytokines have important roles in defence mechanisms against helminths. In this study, the influence of HTLV-1 infection, characterized by a Th1 type of immune response, was evaluated on the cytokine pattern and parasitic specific IgE response in patients with strongyloidiasis. Patients were divided into four groups: strongyloidiasis without HTLV-1 infection, strongyloidiasis with HTLV-1, HTLV-1 without strongyloidiasis and controls without either helminth infection or HTLV-1. The cytokine profile was determined in supernatants of mononuclear cells stimulated with Strongyloides stercoralis crude antigen and the parasite specific IgE was measured by ELISA. Patients coinfected with HTLV-1 had higher levels of interferon (IFN)-gamma and interleukin (IL)-10 (P < 0.05) and lower levels of IL-5 and IgE (P < 0.05) than patients with strongyloidiasis without HTLV-1. There was an inverse relationship between IFN-gamma and IL-5 (P = 0.01; rs = - 0.37) and between IFN-gamma and parasite specific IgE (P = 0.01; rs = - 0.39), and a direct relationship between IFN-gamma and IL-10 (P = 0.04; rs = 0.35). These data show that coinfection with HTLV-1 decreases IL-5 and IgE responses in patients with strongyloidiasis consistent with a relative switch from Th2 to Th1 response. Immunological responses such as these are important in the control of this helminthic infection.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号