CD4-PSEUDOMONAS EXOTOXIN CONJUGATES DELAY BUT DO NOT FULLY INHIBIT HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION IN LYMPHOCYTES INVITRO

被引:14
作者
TSUBOTA, H
WINKLER, G
MEADE, HM
JAKUBOWSKI, A
THOMAS, DW
LETVIN, NL
机构
[1] HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,1 PINE HILL DR,SOUTHBOROUGH,MA 01772
[2] BIOGEN INC,CAMBRIDGE,MA 02142
关键词
Acquired immunodeficiency syndrome therapy; Antiviral drug; HIV; Pseudomonas exotoxin conjugates;
D O I
10.1172/JCI114892
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The CD4 molecule is a high affinity receptor for the human immunodeficiency virus (HIV) envelope glycoprotein (gp160 or gp120). This glycoprotein is expressed on the surface membrane of cells infected with HIV. It has, therefore, been suggested that a soluble form of CD4 might be used as a targeting agent to deliver toxins selectively to cells infected with HIV. We demonstrate that CD4-Pseudomonas exotoxin A (PE) conjugates inhibit the proliferation of gp160-transfected Chinese hamster ovary cells and block HIV replication in virus-infected H9 cells. However, this inhibition of HIV replication appears to be incomplete since virus replication occurs following removal of the toxin conjugates from these cultures. More-over, CD4-PE conjugates delay but do not inhibit HIV replication in human peripheral blood lymphocytes. These studies suggest that such conjugates should be assessed only as potential adjunctive therapies in the acquired immunodeficiency syndrome.
引用
收藏
页码:1684 / 1689
页数:6
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