BLOCKING VIRUS SPREAD BY DCS WITH CARRAGEENAN-BASED COMPOUNDS
用卡拉胶基化合物阻断 DCS 传播的病毒
基本信息
- 批准号:7349006
- 负责人:
- 金额:$ 6.54万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-05-01 至 2007-04-30
- 项目状态:已结题
- 来源:
- 关键词:
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. Early events leading to HIV infection across the mucosa likely involve HIV capture by a wide variety of molecules on the surface of epithelial cells and leukocytes followed by infection of permissive target cells within the tissues. In studying this biology, we are focusing on the contribution of dendritic cells (DCs) and T cells to these events and exploring effective ways to block these complex events in vitro and in vivo. Earlier work confirmed that there are at least two phases of DC-driven transmission of virus to T cells ¿ one involves virus captured by (but not infecting) DCs that is handed directly over to the T cells and the other involves DC infection and the transmission of newly synthesized viruses. Virus captured by DCs is transmitted to CD4 T cells moving rapidly across the synapse naturally created between DCs and T cells. Inclusion of the fusion inhibitor T1249 reduces the amount of virus movement to the T cells, while increasing the amount of virus accumulating in the DCs. The immunologic and virologic consequences of this are under investigation. These data highlight how only blocking certain pathways of virus-DC interactions are suboptimal in preventing DC-driven HIV spread. As a result, additional studies are being performed to test the ability of more broad-acting carrageenan-based formulations for their ability to impede the complex virus-cell interplay needed to facilitate transmission. Carrageenan-based microbicides are promising due to their wide rage of activity against HIV/SIV and other sexually transmitted pathogens. Carrageenans impair virus capture by DCs in vitro and block infection of permissive DC-T cell mixtures. Recent in vivo data revealed that macaques were protected against vaginal SHIV challenge by carrageenan-based microbicides. These data are encouraging for future application of carrageenan-based formulations in preventing HIV spread.
该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金,因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构,不一定是研究者的机构。导致 HIV 跨粘膜感染的早期事件可能涉及 HIV 被上皮细胞和白细胞表面的多种分子捕获,随后感染组织内允许的靶细胞。在研究这一生物学过程中,我们重点关注树突状细胞 (DC) 和 T 细胞对这些事件的贡献,并探索在体外和体内阻断这些复杂事件的有效方法。早期的工作证实,DC驱动的病毒向T细胞的传播至少有两个阶段——一个阶段涉及DC捕获(但不感染)病毒,然后直接传递给T细胞,另一个阶段涉及DC感染和新合成病毒的传播。 DC 捕获的病毒被传播到 CD4 T 细胞,该细胞在 DC 和 T 细胞之间自然产生的突触中快速移动。融合抑制剂 T1249 的加入减少了病毒移动到 T 细胞的数量,同时增加了 DC 中积累的病毒数量。其免疫学和病毒学后果正在研究中。这些数据强调了仅阻断病毒与 DC 相互作用的某些途径对于预防 DC 驱动的 HIV 传播并不是最理想的。因此,正在进行更多研究,以测试更广泛作用的角叉菜胶配方的能力,以了解其阻止促进传播所需的复杂病毒与细胞相互作用的能力。基于角叉菜胶的杀菌剂因其对 HIV/SIV 和其他性传播病原体具有广泛的活性而前景广阔。角叉菜胶在体外削弱 DC 捕获病毒并阻止允许的 DC-T 细胞混合物的感染。最近的体内数据显示,基于角叉菜胶的杀菌剂可以保护猕猴免受阴道 SHIV 的攻击。这些数据对于未来基于角叉菜胶的制剂在预防艾滋病毒传播方面的应用是令人鼓舞的。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Melissa J Robbiani其他文献
Melissa J Robbiani的其他文献
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{{ truncateString('Melissa J Robbiani', 18)}}的其他基金
A novel vaginal ring to prevent HIV and HSV-2 infection, as well as pregnancy
一种预防 HIV 和 HSV-2 感染以及怀孕的新型阴道环
- 批准号:
8450072 - 财政年份:2012
- 资助金额:
$ 6.54万 - 项目类别:
A novel vaginal ring to prevent HIV and HSV-2 infection, as well as pregnancy
一种预防 HIV 和 HSV-2 感染以及怀孕的新型阴道环
- 批准号:
8264696 - 财政年份:2012
- 资助金额:
$ 6.54万 - 项目类别:
HIV ENVELOPE SPECIFIC DARPIN-BASED MICROBICIDE
HIV 包膜特异性 DARPIN 杀菌剂
- 批准号:
8358133 - 财政年份:2011
- 资助金额:
$ 6.54万 - 项目类别:
ZCM:A NOVEL BROAD-SPECTRUM MICROBICIDE FOR SEXUALLY TRANSMITTED INFECTIONS
ZCM:一种治疗性传播感染的新型广谱杀菌剂
- 批准号:
8358089 - 财政年份:2011
- 资助金额:
$ 6.54万 - 项目类别:
BLOCKING VIRUS SPREAD BY DCS WITH CARRAGEENAN-BASED COMPOUNDS
用卡拉胶基化合物阻断 DCS 传播的病毒
- 批准号:
8358043 - 财政年份:2011
- 资助金额:
$ 6.54万 - 项目类别:
DENDRITIC CELL ACTIVATION BY ISS ODN FOR SIV IMMUNITY
ISS ODN 激活树突状细胞以增强 SIV 免疫能力
- 批准号:
8358061 - 财政年份:2011
- 资助金额:
$ 6.54万 - 项目类别:
THE MUCOSAL DENDRITIC CELL-T CELL MILIEU AND SIV SPREAD
粘膜树突状细胞 T 细胞环境和 SIV 传播
- 批准号:
8358075 - 财政年份:2011
- 资助金额:
$ 6.54万 - 项目类别:
HIV ENVELOPE SPECIFIC DARPIN-BASED MICROBICIDE
HIV 包膜特异性 DARPIN 杀菌剂
- 批准号:
8173046 - 财政年份:2010
- 资助金额:
$ 6.54万 - 项目类别:
ZCM:A NOVEL BROAD-SPECTRUM MICROBICIDE FOR SEXUALLY TRANSMITTED INFECTIONS
ZCM:一种治疗性传播感染的新型广谱杀菌剂
- 批准号:
8172989 - 财政年份:2010
- 资助金额:
$ 6.54万 - 项目类别:
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