IN VITRO INACTIVATION OF VIRUSES IN BLOOD COMPONENTS

血液成分中病毒的体外灭活

基本信息

批准号：
2771386
负责人：
GIRISH N VYAS
金额：
$ 42.87万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-09-30 至 2000-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2771386
关键词：
CD4 molecule biotin blood /lymphatic pharmacology blood filtration blood transfusion blood treatment disease /disorder prevention /control disease /disorder proneness /risk enzyme activity human immunodeficiency virus immune complex leukocytes polymerase chain reaction polymers ribozymes virion virus envelope

项目摘要

The risk of transmitting cell-associated human immunodeficiency viruses (HIV- 1/-2), human T cell lymphotropic viruses (HTLV-I/-II), and cytomegaloviruses (CMV), and of transmitting cell-free HIV and hepatitis B and C viruses (HBV and HCV) from fully-screened blood can be reduced by in vitro inactivation/removal (IVIR) of blood-borne viruses (BBV). We propose a three-step cascade process for IVIR of BBV carried out on whole blood during routine blood processing: (1) selective removal of white blood cells, which harbor and permit replication of cell-associated BBV; (2) receptor-mediated removal of the cell-free BBV from leukocyte-free whole blood; and (3) biochemical or chemical inactivation of residual BBV by adding pharmacologically-acceptable agents that are biocompatible with blood. For testing this concept, our experimental design employs HIV as a prototype BBV, because HIV occurs both in cell-associated and cell-free forms and can be monitored quantitatively by complementary in vitro amplifications, biochemically by the polymerase chain reaction (PCR) and biologically by co-cultivation with CD4-positive cells. Because unacceptable platelet loss occurs during leukocyte depletion of whole blood, two different polyester filters are currently used for packed red cells and platelet concentrates. The addition of biotinylated receptor proteins (cD4-CD26) or human antibodies to HIV envelope proteins, bound to streptavidin-coated magnetic beads, will enable specific capture of both cell-free HIV and HIV-immune-complexes from the leukocyte-filtered blood. We will investigate multi-target ribozymes for enzymatic inactivation of HIV RNA and/or ascorbic acid for chemical inactivation of residual virions. Results of the studies with HIV will provide an applicable paradigm for analogous IVIR of cell-free HBV and HCV. Although we do not expect significant changes in membrane structure and function of red cells and platelets, we will perform hematological investigations to validate the safety and effectiveness of blood treatment for IVIR of BBV. Ultimately, our research and development efforts could culminate in a collaboration with manufacturer(s) capable of providing an integrated system suitable for routine IVIR of BBV in transfusion practice.

传播与细胞相关的人免疫缺陷病毒的风险（HIV-1/-2），人类T细胞淋巴病毒（HTLV-I/-II）和巨细胞病毒（CMV），无细胞的HIV和肝炎传播可以减少来自完全筛选的血液的B和C病毒（HBV和HCV）通过体外灭活/去除（IVIR）血传播病毒（BBV）。我们为整个BBV提出了一个三步的级联进程常规血液处理期间的血液：（1）选择性去除白色血细胞携带并允许复制与细胞相关的BBV；（2）从白细胞中除去受体介导的无细胞BBV 全血；（3）残留BBV的生化或化学灭活通过添加具有生物相容性的药理学可接受的剂血。为了测试这个概念，我们的实验设计将艾滋病毒作为原型BBV，因为HIV既出现在细胞相关和无细胞中形式，可以通过体外互补的体外进行定量监测放大，通过聚合酶链反应（PCR）和通过与CD4阳性细胞共培养在生物学上。因为整体白细胞耗竭期间发生不可接受的血小板损失血液，两个不同的聚酯过滤器目前用于填充红色细胞和血小板浓缩物。添加生物素化受体蛋白质（CD4-CD26）或对HIV包膜蛋白的人类抗体，结合对于链霉亲和素涂层的磁珠，将使特定捕获来自白细胞过滤的无细胞HIV和HIV免疫复合物血。我们将研究用于酶促的多目标核酶 HIV RNA和/或抗坏血酸的灭活以灭活化学灭活残留病毒体。艾滋病毒研究的结果将提供适用于无细胞HBV和HCV的类似ivir的适用范例。虽然我们预计膜结构和功能不会发生重大变化红细胞和血小板，我们将进行血液学研究验证血液处理对ivir的安全性和有效性 BBV。最终，我们的研发工作可能最终与能够提供集成的制造商合作适用于输血实践中BBV常规IVIR的系统。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Participating in the evolution of transfusion medicine from a dispensary into a discipline.

参与输血医学从药房到学科的演变。

DOI：
10.1016/j.tmrv.2007.12.005
发表时间：
2008
期刊：
Transfusion medicine reviews
影响因子：
4.5
作者：
Vyas,GirishN
通讯作者：
Vyas,GirishN

Human peripheral blood mononuclear cell substrate for propagating wild type HIV-1.

用于繁殖野生型 HIV-1 的人外周血单核细胞底物。

DOI：
发表时间：
2001
期刊：
Developments in biologicals.
影响因子：
0
作者：
Vyas,GN
通讯作者：
Vyas,GN

Immunobiology of persistent blood-borne viral infections.

持续性血源性病毒感染的免疫生物学。

DOI：
发表时间：
2000
期刊：
Developments in biologicals.
影响因子：
0
作者：
Vyas,GN
通讯作者：
Vyas,GN

Magnesium-mediated reversal of the apparent virucidal effect of ascorbic acid or congo red reacted in vitro with the human immunodeficiency virus.

镁介导的抗坏血酸或刚果红在体外与人类免疫缺陷病毒反应的明显杀病毒作用被逆转。

DOI：
10.1006/biol.1996.0014
发表时间：
1996
期刊：
Biologicals : journal of the International Association of Biological Standardization.
影响因子：
0
作者：
Rawal,BD;Vyas,GN
通讯作者：
Vyas,GN

Hepatitis B virions isolated with antibodies to the pre-S1 domain reveal occult viremia by PCR in Alaska Native HBV carriers who have seroconverted.

用前 S1 结构域抗体分离的乙型肝炎病毒粒子通过 PCR 揭示了血清转化的阿拉斯加本地 HBV 携带者的隐匿性病毒血症。