Search results for "Ribonuclease L"
showing 6 items of 6 documents
Impairment of intracellular antiviral defense with age: age-dependent changes in expression of interferon-induced and double-stranded RNA-activated 2…
1995
The 2',5'-oligoadenylate (2-5A) system is involved in the defense of mammalian cells against virus infection. In a previous study [25], we demonstrated that the activities of the enzymes which synthesize and degrade 2-5A [2-5A synthetase (2-5OAS) and 2',3'-exoribonuclease] and of the enzyme that is activated by 2-5A (ribonuclease L) change during aging and development in different tissues of rat. The age-dependent decrease in 2-5OAS activity and increase in 2-5A nuclease activity results in a decrease in the cellular 2-5A content, suggesting that the efficiency of the antiviral 2-5A system is impaired in aged rats. Here we determined the age-dependent changes in the level of mRNA coding for…
The 2-5A System and HIV Infection
1994
The human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of acquired immunodeficiency syndrome (AIDS). The progression of this retro viral disease is associated with various clinical manifestations, including the acquisition of an immunodeficient state, the frequent presence of neurological disorders, and some malignancies (reviewed in Barre-Sinoussi et al. 1983; Wong-Staal and Gallo 1985; Fauci 1988). Immunologic dysfunctions caused by HIV-1 infection include disorders in the production of cytokines (Murray et al. 1984; Abb et al. 1986). For example, a significant decrease in the production of interferon-α (IFN-α) by cultured peripheral blood mononuclear cells (PBMC) from pat…
(2'-5')Oligoadenylate and intracellular immunity against retrovirus infection.
1992
1. 1. The double-stranded RNA-dependent 2′,5′-oligoadenylate (2–5A) synthetase/ribonuclease L (RNase L) system plays an essential role in the establishment of the antiviral state of a cell exposed to virus infection. 2. 2. Until recently, the application of 2–5A derivatives to reinforce this system seemed to be limited mainly due to the low specificity of RNase L for viral RNA. 3. 3. Two new strategies have been developed which yield a selective antiviral effect of 2–5As at least against human immunodeficiency virus-1 (HIV-1) infection: (i) an “intracellular immunization” appproach using 2-5A synthetase cDNA linked to HIV trans -acting response element (TAR) and (ii) inhibition of retrovira…
Cordycepin analogues of 2',5'-oligoadenylate inhibit human immunodeficiency virus infection via inhibition of reverse transcriptase.
1991
Analogues of 2',5'-oligoadenylates (2-5A), the cordycepin (3'-deoxyadenosine) core trimer (Co3) and its 5'-monophosphate derivative (pCo3), were shown to display pronounced anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro. Treatment of HIV-1 infected H9 cells with 1 microM Co3 or pCo3 resulted in an almost 100% inhibition of virus production. The compounds were encapsulated in liposomes targeted by antibodies specific for the T-cell receptor molecule CD3. Substitution of one or two cordycepin units in Co3 or pCo3 decreased the antiviral activity of the compounds. pCo3 did not stimulate 2-5A-dependent ribonuclease L activity and displayed no effect on the amount of cellular…
Modulation of Nuclear Matrix-associated 2′,5′-Oligoadenylate Metabolism and Ribonuclease L Activity in H9 Cells by Human Immunodeficiency Virus
1989
Human T cells (H9), infected with the HTLV-IIIB strain of the human immunodeficiency virus (HIV-1), have been used to study the alteration of 2',5'-oligoadenylate [2'-5')A) metabolism in relation to virus production. The synthesis of (2'-5')A was determined to proceed in close association with the nuclear matrix. After HIV infection the (2'-5')A synthetase activity increased from 1.1 to 1.5 pmol of (2'-5')A synthesized/100 micrograms of nuclear matrix protein (during a 3-h in vitro incubation period) to 8.2 pmol at day 3 after infection. Then the activity dropped to the initial values. In non-infected H9 cells the (2'-5')A synthetase activity remained unchanged. Simultaneously with the decr…
Mechanism of the Antiretroviral Effect of dsRNA
1994
The development of AIDS seems to be linked to an impairment of processes which are induced or activated by double-stranded RNA (dsRNA), such as the biosynthesis of interferon (IFN), production of 2′,5′-oligoadenylate (2-5A), ribonuclease L (RNase L) activity and different cell-mediated immune functions. A restriction of available bioactive dsRNA (or of dsRNA-dependent enzymes) may play an important role in the disease progression. The results summarized in this review show that defects in dsRNA-dependent pathways exhibited by AIDS patients can be reversed, at least in part, by exogenously supplied dsRNA.