UKY DENTAL COBRE: ORAL INFECTIONS AND HIV RECRUDESCENCE
英国牙科 COBRE:口腔感染和艾滋病毒复发
基本信息
- 批准号:7610647
- 负责人:
- 金额:$ 20.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-08-01 至 2008-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAnti-Retroviral AgentsAutomobile DrivingBacteriaCD4 Positive T LymphocytesCell LineCellsCharacteristicsChloramphenicol O-AcetyltransferaseChronicCoculture TechniquesComputer Retrieval of Information on Scientific Projects DatabaseDataDendritic CellsDentalDiseaseDoseEnzyme-Linked Immunosorbent AssayFibroblastsFundingGenesGingivaGrantHIVHIV InfectionsHIV-1Half-LifeHighly Active Antiretroviral TherapyHumanImmuneIndividualInfectionInstitutionMeasuresModelingOralOutcomePatientsPeriodontitisQuality of lifeReactionRecrudescencesResearchResearch PersonnelResourcesRiskSourceSpecificityStagingSurvival RateSystemT-LymphocyteTimeTreatment ProtocolsUnited States National Institutes of HealthVariantmacrophagemast cellmicrobialoral bacteriaoral infectionpromoterresearch studysuccess
项目摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
The introduction of HAART regimens (Highly Active Antiretroviral Therapy) has significantly modified the course of HIV disease, with longer survival rates and improvement of life quality in HIV-infected individuals. However, complete eradication of HIV infection cannot be achieved with currently available antiretroviral regimens. This primarily results from the establishment of a pool of latently infected CD4+ T cells, macrophages, and other host cells (eg. dendritic cells, mast cells) during the very earliest stages of acute HIV infection that persists with an extremely long half-life. This persistence of HIV-1 within various host immune cells, including macrophages constitutes a major obstacle in the control of HIV-1 infection. We are using model T cell and macrophage systems to evaluate the capacity of the oral microbial challenges to reactivate HIV. Our initial studies have used the BF24 cell line, a human macrophage transfected with the HIV LTR promoter driving a chloramphenicol acetyltransferase (CAT) gene. Specific Aim 1 was to examine the alteration of these cells were challenged with oral bacteria (Pg, Sm, Cr, Fn) or sonicates to assess variations in HIV promoter activation related to species, dose, and time. We also evaluated the ability of a polymicrobial challenge to synergize in this activation. The outcome was measured using a CAT ELISA. Differences were noted in the ability of the various oral bacteria and bacterial sonicates to activate HIV, supporting that the characteristics of oral infection in periodontitis patients could variably impact reactivation of HIV. We also noted that a polybacterial challenge of the BF24 cells demonstrated an additive reactivation when compared to either bacterium alone. Specific Aim 2 focuses on the ability of host induced molecules to reactivate HIV. In these studies, we have challenged human gingival fibroblast (HGF) cultures with various bacterial sonicates. The resulting supernatants were then used to stimulate HIV reactivation in the BF24 cells. The findings indicated a dose and time responsiveness for the HGF supernatants to stimulate the BF24 cells. However, these reactions appeared substantially less that direct bacterial stimulation of the macrophages. Finally, we have initiated some co-culture experiments in which the HGF, macrophages and bacterial challenge take place in the same milieu. Initial results suggest that factors in these cultures may actually modulate the ability to activate the HIV promoter. Thus, the data demonstrate that oral bacteria have the capacity to activate HIV in latently infected macrophages. There appeared some specificity to the magnitude of this activation and a polybacterial challenge of these infected cells can enhance HIV reactivation. The results suggest chronic oral infections provide a risk to treatment success in HIV infected patients.
这个子项目是许多研究子项目中的一个
由NIH/NCRR资助的中心赠款提供的资源。子项目和
研究者(PI)可能从另一个NIH来源获得了主要资金,
因此可以在其他CRISP条目中表示。所列机构为
研究中心,而研究中心不一定是研究者所在的机构。
HAART疗法(高效抗逆转录病毒疗法)的引入显著改变了艾滋病毒疾病的病程,延长了艾滋病毒感染者的生存率,提高了生活质量。然而,用现有的抗逆转录病毒疗法无法完全根除艾滋病毒感染。 这主要是由于建立了潜伏感染的CD 4 + T细胞、巨噬细胞和其他宿主细胞(例如,树突状细胞、肥大细胞),这些细胞在急性HIV感染的最早阶段以极长的半衰期持续存在。 HIV-1在包括巨噬细胞在内的各种宿主免疫细胞内的这种持续存在构成了控制HIV-1感染的主要障碍。 我们正在使用模型T细胞和巨噬细胞系统来评估口腔微生物挑战重新激活HIV的能力。 我们最初的研究使用了BF 24细胞系,这是一种用驱动氯霉素乙酰转移酶(CAT)基因的HIV LTR启动子转染的人巨噬细胞。具体目的1是检查这些细胞的变化,用口腔细菌(Pg,Sm,Cr,Fn)或超声处理物进行攻击,以评估与物种,剂量和时间相关的HIV启动子激活的变化。我们还评估了多微生物挑战在这种激活中协同作用的能力。使用CAT ELISA测量结果。注意到各种口腔细菌和细菌超声处理物激活HIV的能力存在差异,这支持牙周炎患者口腔感染的特征可能会对HIV的重新激活产生负面影响。 我们还注意到,当与单独的细菌相比时,BF 24细胞的多细菌挑战证明了附加的再活化。 具体目标2侧重于宿主诱导分子重新激活HIV的能力。 在这些研究中,我们挑战人类牙龈成纤维细胞(HGF)培养物与各种细菌超声。 然后将所得上清液用于刺激BF 24细胞中的HIV再活化。 结果表明,HGF上清液刺激BF 24细胞的剂量和时间反应性。 然而,这些反应似乎远低于直接细菌刺激巨噬细胞。 最后,我们已经开始了一些共培养实验,其中HGF、巨噬细胞和细菌挑战在相同的环境中发生。 初步结果表明,这些文化中的因素实际上可能调节激活HIV启动子的能力。 因此,这些数据表明,口腔细菌有能力激活潜伏感染的巨噬细胞中的HIV。对这种激活的程度似乎有一些特异性,并且这些感染细胞的多细菌挑战可以增强HIV再激活。结果表明,慢性口腔感染对艾滋病毒感染患者的治疗成功率有风险。
项目成果
期刊论文数量(0)
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Chifu Brad Huang其他文献
Chifu Brad Huang的其他文献
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{{ truncateString('Chifu Brad Huang', 18)}}的其他基金
UKY DENTAL COBRE: ORAL INFECTIONS AND HIV RECRUDESCENCE
英国牙科 COBRE:口腔感染和艾滋病毒复发
- 批准号:
7960552 - 财政年份:2009
- 资助金额:
$ 20.73万 - 项目类别:
Natural Product Protease Inhibitors: Therapeutics for Virulence of Oral Pathogens
天然产物蛋白酶抑制剂:口腔病原体毒力的治疗方法
- 批准号:
7600704 - 财政年份:2009
- 资助金额:
$ 20.73万 - 项目类别:
UKY DENTAL COBRE: ORAL INFECTIONS AND HIV RECRUDESCENCE
英国牙科 COBRE:口腔感染和艾滋病毒复发
- 批准号:
7720970 - 财政年份:2008
- 资助金额:
$ 20.73万 - 项目类别:
Identification of anti-cariogenic/low-glycemic activity factors from Lo Han Kuo
罗汉果抗龋齿/低血糖活性因子的鉴定
- 批准号:
7053449 - 财政年份:2006
- 资助金额:
$ 20.73万 - 项目类别:
UKY DENTAL COBRE: ORAL INFECTIONS AND HIV RECRUDESCENCE
英国牙科 COBRE:口腔感染和艾滋病毒复发
- 批准号:
7382111 - 财政年份:2006
- 资助金额:
$ 20.73万 - 项目类别:
UKY DENTAL COBRE: ORAL INFECTIONS AND HIV RECRUDESCENCE
英国牙科 COBRE:口腔感染和艾滋病毒复发
- 批准号:
7171338 - 财政年份:2005
- 资助金额:
$ 20.73万 - 项目类别:
Novel plant-based Antimicrobials against oral pathogens
针对口腔病原体的新型植物抗菌剂
- 批准号:
6833726 - 财政年份:2004
- 资助金额:
$ 20.73万 - 项目类别:
UKY DENTAL COBRE: ORAL INFECTIONS AND HIV RECRUDESCENCE
英国牙科 COBRE:口腔感染和艾滋病毒复发
- 批准号:
6972166 - 财政年份:2004
- 资助金额:
$ 20.73万 - 项目类别:
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