Comparative analyses of intracellularly expressed antisense RNAs as inhibitors of human immunodeficiency virus type 1 replication

被引:36
作者
Veres, G [1 ]
Junker, U [1 ]
Baker, J [1 ]
Barske, C [1 ]
Kalfoglou, C [1 ]
Ilves, H [1 ]
Escaich, S [1 ]
Kaneshima, H [1 ]
Böhnlein, E [1 ]
机构
[1] Systemix Inc, Palo Alto, CA 94304 USA
关键词
D O I
10.1128/JVI.72.3.1894-1901.1998
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The antiviral activities of intracellularly expressed antisense RNAs complementary to the human immunodeficiency virus tape 1 (HIV-1) pol, vif, and env genes and the 3' long terminal repeat (LTR) sequence were evaluated in this comparative study, Retroviral vectors expressing the antisense RNAs as part of the Moloney murine leukemia virus LTR promoter-directed retroviral transcript were constructed. The CD4(+) T-cell line CEM-SS was transduced with retroviral constructs, and Northern blot analyses showed high steady-state antisense RNA expression levels, The most efficient inhibition of HIV-1 replication was observed with the env antisense RNA, followed by the pol complementary sequence, leading to 2- to 3-log(10) reductions in p24 antigen production even at high inoculation doses (4 x 10(4) 50% tissue culture infective doses) of the HIV-1 strain HXB3. The strong antiviral effect correlated with a reduction of HIV-1 steady-state RNA levels, and with intracellular Tat protein production, suggesting that antisense transcripts act at an early step of HIV-1 replication. A lower steady-state antisense RNA level was detected in transduced primary CD4(+) lymphocytes than in CEM-SS cells, Nevertheless, replication of the HIV-1 JR-CSF isolate was reduced with both the pol and env antisense RNA, Intracellularly expressed antisense sequences demonstrated more pronounced antiviral efficacy than the trans-dominant RevM10 protein, making these antisense RNAs a promising gene therapy strategy for HIV-1.
引用
收藏
页码:1894 / 1901
页数:8
相关论文
共 39 条
[1]   COMPARISON OF TRANSDOMINANT INHIBITORY MUTANT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GENES EXPRESSED BY RETROVIRAL VECTORS IN HUMAN T-LYMPHOCYTES [J].
BAHNER, I ;
ZHOU, C ;
YU, XJ ;
HAO, QL ;
GUATELLI, JC ;
KOHN, DB .
JOURNAL OF VIROLOGY, 1993, 67 (06) :3199-3207
[2]   GENE-THERAPY - INTRACELLULAR IMMUNIZATION [J].
BALTIMORE, D .
NATURE, 1988, 335 (6189) :395-396
[3]   INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN HUMAN T-CELLS BY RETROVIRAL-MEDIATED GENE-TRANSFER OF A DOMINANT-NEGATIVE REV TRANSACTIVATOR [J].
BEVEC, D ;
DOBROVNIK, M ;
HAUBER, J ;
BOHNLEIN, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (20) :9870-9874
[4]   A new antisense tRNA construct for the genetic treatment of human immunodeficiency virus type 1 infection [J].
Biasolo, MA ;
Radelli, A ;
DelPup, L ;
Franchin, E ;
DeGiuliMorghen, C ;
Palu, G .
JOURNAL OF VIROLOGY, 1996, 70 (04) :2154-2161
[5]   DUAL-TARGET INHIBITION OF HIV-1 INVITRO BY MEANS OF AN ADENOASSOCIATED VIRUS ANTISENSE VECTOR [J].
CHATTERJEE, S ;
JOHNSON, PR ;
WONG, KK .
SCIENCE, 1992, 258 (5087) :1485-1488
[6]  
CHOLI H, 1994, ANTISENSE RES DEV, V4, P19
[7]   REVM10-MEDIATED INHIBITION OF HIV-1 REPLICATION IN CHRONICALLY INFECTED T-CELLS [J].
ESCAICH, S ;
KALFOGLOU, C ;
PLAVEC, I ;
KAUSHAL, S ;
MOSCA, JD ;
BOHNLEIN, E .
HUMAN GENE THERAPY, 1995, 6 (05) :625-634
[8]  
FORESTELL SP, 1997, GENE THER, V4, P19
[9]   INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION IN A HUMAN T-CELL LINE BY ANTISENSE RNA EXPRESSED IN THE CELL [J].
GYOTOKU, JI ;
ELFARRASH, MA ;
FUJIMOTO, S ;
GERMERAAD, WTV ;
WATANABE, Y ;
TESHIGAWARA, K ;
HARADA, S ;
KATSURA, Y .
VIRUS GENES, 1991, 5 (03) :189-202
[10]   INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MULTIPLICATION BY ANTISENSE AND SENSE RNA EXPRESSION [J].
JOSHI, S ;
VANBRUNSCHOT, A ;
ASAD, S ;
VANDERELST, I ;
READ, SE ;
BERNSTEIN, A .
JOURNAL OF VIROLOGY, 1991, 65 (10) :5524-5530