共查询到20条相似文献,搜索用时 17 毫秒
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Replication-competent viruses have the potential to overcome the delivery barrier in tumors that has plagued traditional gene-therapy
approaches to cancer treatment. However, recent clinical data suggests that a cytokine-based immune response against the virus-infected
tumor cells may severely limit the efficacy of the replication-competent approach. This paper generalizes our earlier spatial
model to incorporate an immune response against the infected tumor cells. An approximate but accurate condition is derived
for the virus—if uniformly injected throughout the tumor—to eradicate the tumor in the presence of the immune response. To
validate the model using clinical data describing the temporal interaction of tumor necrosis factor and free virus in the
plasma, we needed the immune response to be time-delayed and experience either saturated stimulation or second-order clearance.
The resulting estimates of some unknown parameters provide some implications for the delivery of treatment. 相似文献
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The interaction between viral protein and host actin facilitates the virus infection to host 总被引:1,自引:0,他引:1
Although the virus-host interaction has attracted extensive studies, the host proteins essential for virus infection remain largely unknown. To address this issue, the shrimp Penaeus stylirostris densovirus (PstDNV), belonging to the family Parvoviridae, was characterized. PstDNV, a single-stranded DNA virus with a 3.9-kb genome, encoded only three open reading frames (ORFs). Among the three viral proteins, the PstDNV ORF2-encoded protein was discovered to interact with the shrimp actin, suggesting that the host actin played a very important role in virus infection. The RNAi assays revealed that the ORF2-encoded protein was required for the PstDNV infection. The confocal evidence demonstrated that the interaction between the ORF2-encoded protein and actin was essential for the virus infection. Therefore our study indicated that the manipulation of the host actin cytoskeleton was a necessary strategy for viral pathogens to invade host cells. 相似文献
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Phosphorylation coexists with O‐GlcNAcylation in a plant virus protein and influences viral infection
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Sandra Martínez‐Turiño José De Jesús Pérez Marta Hervás Rosana Navajas Sergio Ciordia Namrata D. Udeshi Jeffrey Shabanowitz Donald F. Hunt Juan Antonio García 《Molecular Plant Pathology》2018,19(6):1427-1443
Phosphorylation and O‐GlcNAcylation are two widespread post‐translational modifications (PTMs), often affecting the same eukaryotic target protein. Plum pox virus (PPV) is a member of the genus Potyvirus which infects a wide range of plant species. O‐GlcNAcylation of the capsid protein (CP) of PPV has been studied extensively, and some evidence of CP phosphorylation has also been reported. Here, we use proteomics analyses to demonstrate that PPV CP is phosphorylated in vivo at the N‐terminus and the beginning of the core region. In contrast with the ‘yin–yang’ mechanism that applies to some mammalian proteins, PPV CP phosphorylation affects residues different from those that are O‐GlcNAcylated (serines Ser‐25, Ser‐81, Ser‐101 and Ser‐118). Our findings show that PPV CP can be concurrently phosphorylated and O‐GlcNAcylated at nearby residues. However, an analysis using a differential proteomics strategy based on iTRAQ (isobaric tags for relative and absolute quantitation) showed a significant enhancement of phosphorylation at Ser‐25 in virions recovered from O‐GlcNAcylation‐deficient plants, suggesting that crosstalk between O‐GlcNAcylation and phosphorylation in PPV CP takes place. Although the preclusion of phosphorylation at the four identified phosphotarget sites only had a limited impact on viral infection, the mimicking of phosphorylation prevents PPV infection in Prunus persica and weakens infection in Nicotiana benthamiana and other herbaceous hosts, prompting the emergence of potentially compensatory second mutations. We postulate that the joint action of phosphorylation and O‐GlcNAcylation in the N‐proximal segment of CP allows a fine‐tuning of protein stability, providing the amount of CP required in each step of viral infection. 相似文献
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Control of heterologous hepatitis C virus infection in chimpanzees is associated with the quality of vaccine-induced peripheral T-helper immune response 总被引:5,自引:0,他引:5
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Rollier C Depla E Drexhage JA Verschoor EJ Verstrepen BE Fatmi A Brinster C Fournillier A Whelan JA Whelan M Jacobs D Maertens G Inchauspé G Heeney JL 《Journal of virology》2004,78(1):187-196
Prophylactic hepatitis C virus (HCV) vaccine trials with human volunteers are pending. There is an important need for immunological end points which correlate with vaccine efficacy and which do not involve invasive procedures, such as liver biopsies. By using a multicomponent DNA priming-protein boosting vaccine strategy, na?ve chimpanzees were immunized against HCV structural proteins (core, E1, and E2) as well as a nonstructural (NS3) protein. Following immunization, exposure to the heterologous HCV 1b J4 subtype resulted in a peak of plasma viremia which was lower in both immunized animals. Compared to the na?ve infection control and nine additional historical controls which became chronic, vaccinee 2 (Vac2) rapidly resolved the infection, while the other (Vac1) clearly controlled HCV infection. Immunization induced antibodies, peptide-specific gamma interferon (IFN-gamma), protein-specific lymphoproliferative responses, IFN-gamma, interleukin-2 (IL-2), and IL-4 T-helper responses in both vaccinees. However, the specificities were markedly different: Vac2 developed responses which were lower in magnitude than those of Vac1 but which were biased towards Th1-type cytokine responses for E1 and NS3. This proof-of-principle study in chimpanzees revealed that immunization with a combination of nonstructural and structural antigens elicited T-cell responses associated with an alteration of the course of infection. Our findings provide data to support the concept that the quality of the response to conserved epitopes and the specific nature of the peripheral T-helper immune response are likely pivotal factors influencing the control and clearance of HCV infection. 相似文献
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Transient mobilization of human immunodeficiency virus (HIV)-specific CD4 T-helper cells fails to control virus rebounds during intermittent antiretroviral therapy in chronic HIV type 1 infection 总被引:5,自引:0,他引:5
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Carcelain G Tubiana R Samri A Calvez V Delaugerre C Agut H Katlama C Autran B 《Journal of virology》2001,75(1):234-241
Immune control of human immunodeficiency virus (HIV) is not restored by highly active antiretroviral therapies (HAART) during chronic infection. We examined the capacity of repeated structured therapeutic interruptions (STI) to restore HIV-specific CD4 and CD8 T-cell responses that controlled virus production. Eleven STI (median duration, 7 days; ranges, 4 to 24 days) were performed in three chronically HIV-infected patients with CD4 counts above 400/mm(3) and less than 200 HIV RNA copies/ml after 18 to 21 months of HAART; treatment resumed after 1 week or when virus became detectable. HIV-specific T-cell responses were analyzed by proliferation, gamma interferon (IFN-gamma) production, and enzyme-linked immunospot assays. Seven virus rebounds were observed (median, 4,712 HIV-1 RNA copies/ml) with a median of 7 days during which CD4 and CD8 counts did not significantly change. After treatment resumed, the viral load returned below 200 copies/ml within 3 weeks. Significant CD4 T-cell proliferation and IFN-gamma production against HIV p24 appeared simultaneously with or even before the virus rebounds in all patients. These CD4 responses lasted for less than 3 weeks and disappeared before therapeutic control of the virus had occurred. Increases in the numbers of HIV-specific CD8 T cells were delayed compared to changes in HIV-specific CD4 T-cell responses. No delay or increase in virus doubling time was observed after repeated STI. Iterative reexposure to HIV during short STI in chronically infected patients only transiently mobilized HIV-specific CD4 T1-helper cells, which might be rapidly altered by virus replication. Such kinetics might explain the failure at delaying subsequent virus rebounds and raises concerns about strategies based on STI to restore durable HIV-specific T-cell responses in chronic HIV infection. 相似文献
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Alexander-Miller MA 《Cellular immunology》2000,201(1):58-62
The importance of high avidity CTL for the effective clearance of viral infections is now well established. Thus one would predict that the preferential activation and expansion of high avidity CTL following viral challenge and retention of these cells in the memory pool would be optimal for the immune response. However, whether this actually occurs during the immune response to viral infection is unknown. In this report I have analyzed the avidity of the CTL specific for the OVA(257-264) peptide during acute infection with a recombinant vaccinia expressing ovalbumin and in the memory population. I have found that the relative ratio of high and low avidity CTL varies over the course of an immune response. Thus CTL avidity is an important factor in the expansion and survival of CTL in vivo. 相似文献
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流感病毒感染可引起肺部损伤甚至引发严重的并发症,因其抗原性易发生变异,所以疫苗难以进行全面防护。而肠道菌群具有促进免疫系统正常发育及调节免疫细胞内稳态的功能。本文综述了肠道菌群与流感病毒的相互作用和影响,从肠道菌群提高人体固有免疫反应、减轻肺部免疫损伤、促使树突状细胞成熟及形成同源异型交叉保护等方面,探讨肠道菌群对流感病毒感染的预防和治疗作用及其机制,旨在为将肠道菌群作为预防治疗疾病手段和潜在的药物靶点提供思路。 相似文献
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Integration of viral DNA into the host genome is a central event in the replication cycle and the pathogenesis of retroviruses, including HIV. Although most cells infected with HIV are rapidly eliminated in vivo, HIV also infects long-lived cells that persist during combination antiretroviral therapy (cART). Cells with replication competent HIV proviruses form a reservoir that persists despite cART and such reservoirs are at the center of efforts to eradicate or control infection without cART. The mechanisms of persistence of these chronically infected long-lived cells is uncertain, but recent research has demonstrated that the presence of the HIV provirus has enduring effects on infected cells. Cells with integrated proviruses may persist for many years, undergo clonal expansion, and produce replication competent HIV. Even proviruses with defective genomes can produce HIV RNA and may contribute to ongoing HIV pathogenesis. New analyses of HIV infected cells suggest that over time on cART, there is a shift in the composition of the population of HIV infected cells, with the infected cells that persist over prolonged periods having proviruses integrated in genes associated with regulation of cell growth. In several cases, strong evidence indicates the presence of the provirus in specific genes may determine persistence, proliferation, or both. These data have raised the intriguing possibility that after cART is introduced, a selection process enriches for cells with proviruses integrated in genes associated with cell growth regulation. The dynamic nature of populations of cells infected with HIV during cART is not well understood, but is likely to have a profound influence on the composition of the HIV reservoir with critical consequences for HIV eradication and control strategies. As such, integration studies will shed light on understanding viral persistence and inform eradication and control strategies. Here we review the process of HIV integration, the role that integration plays in persistence, clonal expansion of the HIV reservoir, and highlight current challenges and outstanding questions for future research. 相似文献
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RNA病毒利用外泌体促进病毒感染的研究进展 总被引:2,自引:0,他引:2
外泌体是一种由细胞主动向胞外分泌的囊泡类小体,因其能在细胞间传递蛋白、脂类和核酸等分子,而被认为是一种新的重要的细胞间通讯方式。RNA病毒,如HIV-1、HCV等,作为一类重要的病原体,一直影响着全人类的健康。近来的研究发现,病毒能够利用外泌体的某些相关功能促进其复制与传播。然而,对外泌体与病毒感染的相关研究才刚刚起步,尚有很多方面并未被详细认知,所要研究的内容还有很多。本文主要总结了外泌体在一些RNA病毒感染中的促进作用及其可能的机制,以期让大家了解RNA病毒与外泌体之间已有的相互关系。 相似文献
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Larin FI Lebedev VV Red'ko AN 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》2005,(3):78-79
The analysis of the morbidity dynamics of HIV infection, hepatitis B and C in the Krasnodar territory for 1996-2003 is presented. The tendency of strengthening direct correlation between age-dependent rates in these groups of diseases has been established. The correlation coefficient (rxy) is at present +0.851 (HIV infection-virus hepatitis B) and +0.892 (HIV infection-virus hepatitis C). The highest levels of primary morbidity are registered in persons aged 20-39 years. The established epidemiological parallels between HIV infection and parenteral hepatitis require the development of the unified strategy of the prophylaxis of these diseases on the federal and regional levels. 相似文献
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The accumulating evidence indicates that the viral structural proteins play critical roles in virus infection. However, the interaction between the viral structural protein and host cytoskeleton protein in virus infection remains to be addressed. In this study, the viral VP466 protein, one of the major structural proteins of shrimp white spot syndrome virus (WSSV), was characterized. The results showed that the suppression of VP466 gene expression led to the inhibition of WSSV infection in shrimp, indicating that the VP466 protein was required in virus invasion. It was found that the VP466 protein was interacted with the host cytoskeleton protein tropomyosin. As documented, the VP466–tropomyosin interaction facilitated the WSSV infection. Therefore our findings revealed a novel molecular mechanism in the virus invasion to its host, which would be helpful to better understand the molecular events in virus infection in invertebrate. 相似文献