ANTI-HIV AND ANTITUMOR ACTIVITIES OF RECOMBINANT MAP30 FROM BITTER-MELON

被引:160
作者
LEEHUANG, S
HUANG, PL
CHEN, HC
HUANG, PL
BOURINBAIAR, A
HUANG, HI
KUNG, HF
机构
[1] NYU,SCH MED,DEPT BIOCHEM,NEW YORK,NY 10016
[2] AMER BIOSCI,NEW YORK,NY 10021
[3] NICHHD,BETHESDA,MD 20892
[4] NCI,FREDERICK CANC RES & DEV CTR,DCT,BIOL RESPONSE MODIFIERS PROGRAM,BIOCHEM PHYSIOL L,FREDERICK,MD 21701
关键词
MOMORDICA CHARANTIA; RECOMBINANT ANTIVIRAL AGENT; CLONING; EXPRESSION;
D O I
10.1016/0378-1119(95)00186-A
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
MAP30 is an anti-HIV plant protein that we have identified and purified to homogeneity from bitter melon (Momordica charantia). It is capable of acting against multiple stages of the viral life cycle, on acute infection as well as replication in chronically infected cells. In addition to antiviral action, MAP30 also possesses anti-tumor activity, topological inactivation of viral DNA, inhibition of viral integrase and cell-free ribosome-inactivation activities. We have cloned and expressed the MAP30 gene, The objective of this study is to characterize recombinant MAP30 (re-MAP30) and to determine its anti-HIV, anti-tumor and other activities. We report here that re-MAP30 inhibits HIV-1 and certain human tumors to the same extent as its native counterpart, natural MAP30 (nMAP30). The anti-HIV activity was measured by quantitative focal syncytium formation on CEM-ss cell monolayers, viral core protein p24 expression and viral-associated reverse transcriptase activity in HIV-1-infected H9 cells. The anti-tumor activity was measured by metabolic labeling of protein synthesis in tumor cells. In the dose range of the assay, re-MAP30 exhibits little toxicity to the uninfected viral target cells and other normal human cells. Identical to nMAP30, re-MAP30 is also active in topological inactivation of viral DNA, inhibition of viral DNA integration and cell-free ribosome inactivation. The cloning and expression of the gene encoding biologically active re-MAP30 provides an abundant source of homogeneous material for clinical investigations, as well as structure-function studies of this novel antiviral and anti-tumor agent.
引用
收藏
页码:151 / 156
页数:6
相关论文
共 23 条
[1]   LIPID-COMPOSITION AND FLUIDITY OF THE HUMAN IMMUNODEFICIENCY VIRUS [J].
ALOIA, RC ;
JENSEN, FC ;
CURTAIN, CC ;
MOBLEY, PW ;
GORDON, LM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (03) :900-904
[2]   UNEXPECTED ACTIVITY OF SAPORINS [J].
BARBIERI, L ;
GORINI, P ;
VALBONESI, P ;
CASTIGLIONI, P ;
STIRPE, F .
NATURE, 1994, 372 (6507) :624-624
[3]   MEMBRANE LEAKINESS AFTER VIRAL-INFECTION AND A NEW APPROACH TO DEVELOPMENT OF ANTI-VIRAL AGENTS [J].
CARRASCO, L .
NATURE, 1978, 272 (5655) :694-699
[4]   PERTURBATION OF HOST-CELL MEMBRANE IS A PRIMARY MECHANISM OF HIV CYTOPATHOLOGY [J].
CLOYD, MW ;
LYNN, WS .
VIROLOGY, 1991, 181 (02) :500-511
[5]  
ENDO Y, 1987, J BIOL CHEM, V262, P5908
[6]  
ENDO Y, 1987, J BIOL CHEM, V262, P8218
[7]  
FOATOMASI L, 1982, ARCH VIROL, V71, P322
[8]  
GREVER MR, 1992, SEMIN ONCOL, V19, P622
[9]  
HO KKW, 1991, BIOCHIM BIOPHYS ACTA, V1088, P311
[10]  
HOFFMAN AD, 1985, VIROLOGY, V47, P326