LAB ADAPTATION IN HIV-1
HIV-1 的实验室适应
基本信息
- 批准号:2671636
- 负责人:
- 金额:$ 3.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1998
- 资助国家:美国
- 起止时间:1998-07-01 至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Goals of this proposal include elucidating the role that CD4 affinity of
HIV-1 gp120 plays in determining lab adapted or primary phenotype,
generating cell lines which will support the growth of T-cell tropic
isolates, and establishing quantitative infectivity assays with which to
analyze macrophage-tropic isolates of HIV-1. It is proposed to dissect
out distinct mutational changes that occur in gp120 as HIV-1 undergoes
lab adaptation, and to compare infectious properties, and gp120
biochemical attributes such as CD4 affinity, to those of the parental
primary isolate, thus gaining insight into ways to grow primary isolates.
T-cell lines capable of supporting primary isolate growth will be
generated by using a retroviral vector to introduce high amounts of CD4
into leukemic T-cell lines, thus making it easier for primary isolates
to attach to and establish an infection. A quantitative infectivity assay
for macrophage-tropic isolates of HIV-1 will be established by expressing
CD44S in adherent cell lines such as HeLa CD4 or CEM-SS. The most
susceptible line will be used for infectivity assays. Soluble CD4 and
gp120 subunit vaccines (both based and initially tested on lab adapted
strains) have failed to inactivate primary strains of HIV- 1.
Understanding how infectious properties of primary isolates differ from
those of lab adapted isolates will aid in the development of cell culture
systems allowing propagation of primary strains of HIV-1 for use in the
development of vaccines and other antiviral strategies.
该提案的目标包括阐明CD4亲和力在细胞内的作用。
HIV-1 gp120在确定实验室适应或主要表型中起作用,
产生将支持T细胞嗜性的生长的细胞系,
分离株,并建立定量感染性测定,
分析嗜巨噬细胞的HIV-1分离株。建议解剖
当HIV-1经历了一系列的突变后,
实验室适应性,并比较感染性,以及GP 120
生物化学属性,如CD4亲和力,对那些父母
初级分离物,从而深入了解如何培养初级分离物。
能够支持原代分离株生长的T细胞系将被
通过使用逆转录病毒载体引入大量的CD4
白血病T细胞系,从而使其更容易为主要分离物
附着并造成感染定量感染性测定
对于嗜巨噬细胞的HIV-1分离株,
粘附细胞系如HeLa CD4或CEM-SS中的CD44 S。最
敏感品系将用于感染性试验。可溶性CD4和
gp120亚单位疫苗(基于实验室改造的
菌株)未能消除HIV-1的主要菌株。
了解原代分离株的感染特性与
实验室适应的分离物的那些将有助于细胞培养的发展
允许HIV-1的原代菌株繁殖的系统,
开发疫苗和其他抗病毒策略。
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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