The interleukin-2 fusion protein, DAB(389)IL-2, inhibits the development of infectious virus in human immunodeficiency virus type 1-infected human peripheral blood mononuclear cells

被引:6
作者
Zhang, LJ [1 ]
Waters, CA [1 ]
Poisson, LR [1 ]
Estis, LF [1 ]
Crumpacker, CS [1 ]
机构
[1] SERAGEN INC, HOPKINTON, MA USA
关键词
D O I
10.1086/513972
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
DAB(389)IL-2 is a genetically engineered fusion protein that reduces human immunodeficiency virus type 1 (HIV-1) replication in activated, interleukin (IL)-2 receptor (IL-2R)-expressing human peripheral blood mononuclear cells (PBMC). The level of infectious virus released by cultured PBMC after treatment with DAB(389)IL-2 was measured by a quantitative microculture assay. The inhibition of p24 antigen production was also evaluated in cultures that differed in duration of infection and activation state. Although the activation state of the cell and the time of DAB(389)IL-2 addition to the cultures influenced its anti-HIV activity, DAB(389)IL-2 treatment decreased levels of infectious HIV-1 to 0.1%-6.5% of untreated cell levels. DAB(389)IL-2 also decreased p24 antigen expression to 10%-48% of controls, even when added as late as 8 days after acute infection. Mutational variants of DAB(389)IL-2 that lack catalytic activity or IL-2R binding are without anti-HIV activity.
引用
收藏
页码:790 / 794
页数:5
相关论文
共 15 条
[1]  
*AIDS, 1994, ACTG VIR MAN HIV LAB, P1
[2]  
BURKRINSKY MI, 1991, SCIENCE, V254, P423
[3]   HIV-1 ENVELOPE GLYCOPROTEINS INDUCE ACTIVATION OF ACTIVATED PROTEIN-1 IN CD4+ T-CELLS [J].
CHIRMULE, N ;
GOONEWARDENA, H ;
PAHWA, S ;
PASIEKA, R ;
KALYANARAMAN, VS ;
PAHWA, S .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (33) :19364-19369
[4]   IN-VIVO EMERGENCE OF HIV-1 VARIANTS RESISTANT TO MULTIPLE PROTEASE INHIBITORS [J].
CONDRA, JH ;
SCHLEIF, WA ;
BLAHY, OM ;
GABRYELSKI, LJ ;
GRAHAM, DJ ;
QUINTERO, JC ;
RHODES, A ;
ROBBINS, HL ;
ROTH, E ;
SHIVAPRAKASH, M ;
TITUS, D ;
YANG, T ;
TEPPLER, H ;
SQUIRES, KE ;
DEUTSCH, PJ ;
EMINI, EA .
NATURE, 1995, 374 (6522) :569-571
[5]   SELECTIVE ELIMINATION OF HIV-1-INFECTED CELLS WITH AN INTERLEUKIN-2 RECEPTOR SPECIFIC CYTOTOXIN [J].
FINBERG, RW ;
WAHL, SM ;
ALLEN, JB ;
SOMAN, G ;
STROM, TB ;
MURPHY, JR ;
NICHOLS, JC .
SCIENCE, 1991, 252 (5013) :1703-1705
[6]   HIV-I INFECTION OF NONDIVIDING CELLS - C-TERMINAL TYROSINE PHOSPHORYLATION OF THE VIRAL MATRIX PROTEIN IS A KEY REGULATOR [J].
GALLAY, P ;
SWINGLER, S ;
AIKEN, C ;
TRONO, D .
CELL, 1995, 80 (03) :379-388
[7]   THE VPR PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFLUENCES NUCLEAR-LOCALIZATION OF VIRAL NUCLEIC-ACIDS IN NONDIVIDING HOST-CELLS [J].
HEINZINGER, NK ;
BUKRINSKY, MI ;
HAGGERTY, SA ;
RAGLAND, AM ;
KEWALRAMANI, V ;
LEE, MA ;
GENDELMAN, HE ;
RATNER, L ;
STEVENSON, M ;
EMERMAN, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (15) :7311-7315
[8]   SERUM INCREASES AND LYMPHOID-CELL SURFACE LOSSES OF IL-2 RECEPTOR CD25 IN HIV-INFECTION - DISTINCTIVE PARAMETERS OF HIV-INDUCED CHANGE [J].
HOFMANN, B ;
NISHANIAN, P ;
FAHEY, JL ;
ESMAIL, I ;
JACKSON, AL ;
DETELS, R ;
CUMBERLAND, W .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1991, 61 (02) :212-224
[9]   STIMULATION OF AIDS LYMPHOCYTES WITH CALCIUM IONOPHORE-(A23187) AND PHORBOL ESTER (PMA) - STUDIES OF CYTOPLASMIC FREE CA, IL-2 RECEPTOR EXPRESSION, IL-2 PRODUCTION, AND PROLIFERATION [J].
HOFMANN, B ;
MOLLER, J ;
LANGHOFF, E ;
JAKOBSEN, KD ;
ODUM, N ;
DICKMEISS, E ;
RYDER, LP ;
THASTRUP, O ;
SCHARFF, O ;
FODER, B ;
PLATZ, P ;
PETERSEN, C ;
MATHIESEN, L ;
HARTVIGJENSEN, T ;
SKINHOJ, P ;
SVEJGAARD, A .
CELLULAR IMMUNOLOGY, 1989, 119 (01) :14-21
[10]  
KATZENSTEIN DA, 1995, AIDS CLIN REV, V96, P277