| Autor: |
Veres, Gabor, Junker, Uwe, Baker, Jenny, Barske, Carmen, Kalfoglou, Creton, Ilves, Heini, Escaich, Sonia, Kaneshima, Hideto, Bo¨hnlein, Ernst |
| Zdroj: |
The Journal of Virology; March 1998, Vol. 72 Issue: 3 p1894-1901, 8p |
| Abstrakt: |
ABSTRACTThe antiviral activities of intracellularly expressed antisense RNAs complementary to the human immunodeficiency virus type 1 (HIV-1) pol, vif, and envgenes 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 theenvantisense RNA, followed by the polcomplementary sequence, leading to 2- to 3-log10reductions in p24 antigen production even at high inoculation doses (4 × 10450% 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 poland envantisense RNA. Intracellularly expressed antisense sequences demonstrated more pronounced antiviral efficacy than thetrans-dominant RevM10 protein, making these antisense RNAs a promising gene therapy strategy for HIV-1. |
| Databáze: |
Supplemental Index |
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