Skip to main content
SpringerLink
Log in

The 2-5A System and HIV Infection

  • Chapter
Biological Response Modifiers — Interferons, Double-Stranded RNA and 2′,5′-Oligoadenylates

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 14))

Abstract

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 Barré-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 patients infected with HIV-1 has been reported (Rossol et al. 1989; Voth et al. 1990). In addition, the production of IFN-γ is decreased in patients at late CDC stage III and CDC IV (Rossol et al. 1989). However, at late stages of the disease, the IFN-γ levels and, in particular, IFN-a levels increase (Buimovici-Klein et al. 1986; Skidmore and Mawson 1987; Rossol et al. 1989). Recent results suggest that HIV is capable of inducing in vitro production of conventional acid-stabile IFN-a, while only low levels of acid-labile IFN-α are present in sera of patients with AIDS-related complex (ARC) and AIDS (Capobianchi et al. 1988). There are also some hints that one enzyme of the 2′,5′-oligoadenylate (2-5A) pathway, the ribonuclease L (RNase L), is inactive in blood lymphocytes of AIDS patients (Carter et al. 1987), despite a high level of its activator 2-5A, indicating the presence of an inhibitor in HIV-infected cells which interferes with the proper functioning of this antiviral pathway. Therefore restoration of the natural 2-5A synthetase (2-5OAS)/RNase L and dsRNA-dependent protein kinase pathways may help to overcome the depressed immune status of ARC and AIDS patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abb J, Piechowiak H, Zachoval R, Zachoval V, Deinhardt F (1986) Infection with human T-lymphotropic virus type III and leukocyte interferon production of homosexual men. Eur J Clin Microbiol 5:365–368.

    Article  PubMed  CAS  Google Scholar 

  • Baba M, Pauwels R, Balzarini J, Schols D, De Clercq E (1989) Coumermycin Al is a potent inhibitor of human immunodeficiency virus (HIV) replication in vitro. Int J Exp Clin Chemother 2:15–20.

    CAS  Google Scholar 

  • Baglioni C, Minks MA, Maroney PA (1978) Interferon action may be mediated by activation of a nuclease by pppA2′p5′A2′p5′A. Nature 273:684–687.

    Article  PubMed  CAS  Google Scholar 

  • Baglioni C, Maroney PA, West DK (1979) 2′5′Oligo(A) polymerase activity and inhibition of viral RNA synthesis in interferon-treated HeLa cells. Biochemistry 18:1765–1770.

    Article  PubMed  CAS  Google Scholar 

  • Baglioni C, De Benedetti A, Williams GJ (1984) Cleavage of nascent reovirus mRNA by localized activation of the 2′-5′-oligoadenylate-dependent endoribonuclease. J Virol 52:865–871.

    PubMed  CAS  Google Scholar 

  • Barat C, Lullien V, Schatz O, Keith G, Nugeyre MT, Grüninger-Leitch F, Barré-Sinoussi F, LeGrice SFJ, Darlix JL (1989) HIV-1 reverse transcriptase specifically interacts with the anticodon domain of its cognate primer tRNA. EMBO J 8:3279–3285.

    PubMed  CAS  Google Scholar 

  • Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L (1983) Isolation of a Tlymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–871.

    Article  PubMed  Google Scholar 

  • Bayard B, Bisbal C, Silhol M, Cnockaert J, Huez G, Lebleu B (1984) Increased stability and antiviral activity of 2′-O-phosphoglyceryl derivatives of (2′-5′)oligo(adenylate). Roles of phosphodies-terases and phosphatases in (2′-5′)oligo(adenylate) catabolism. Eur J Biochem 142:291–298.

    Article  PubMed  CAS  Google Scholar 

  • Bayard B, Leserman LD, Bisbal C, Lebleu B (1985) Antiviral activity in L1210 cells of liposome-encapsulated (2′-5′)oligo(adenylate) analogues. Eur J Biochem 151:319–325.

    Article  PubMed  CAS  Google Scholar 

  • Bednarik DP, Mosca JD, Raj NBK, Pitha PM (1989) Inhibition of human immunodeficiency virus (HIV) replication by HIV-trans-activated α2-interferon. Proc Natl Acad Sci USA 86:4958–4962.

    Article  PubMed  CAS  Google Scholar 

  • Benech P, Mory Y, Revel M, Chebath J (1985) Structure of two forms of the interferon-induced (2′-5′)oligo A synthetase of human cells based on cDNAs and gene sequences. EMBO J 4:2249–2256.

    PubMed  CAS  Google Scholar 

  • Bisbal C, Salehzada T, Lebleu B, Bayard B (1989) Characterization of two murine (2′-5′)(A)n-dependent endonucleases of different molecular mass. Eur J Biochem 179:595–602.

    Article  PubMed  CAS  Google Scholar 

  • Buimovici-Kleim E, Lange M, Klein RJ, Grieeo MH, Cooper LZ (1986) Long-term follow-up of serum interferon and its acid stability in a group of homosexual men. AIDS Res 2:99–108.

    Article  Google Scholar 

  • Capobianchi MR, De Marco F, Di Marco P, Dianzani F (1988) Acid-labile human interferon alpha production by peripheral blood mononuclear cells stimulated by HIV-infected cells. Arch Virol 99:1–19.

    Article  Google Scholar 

  • Carter WA, Strayer DR, Brodsky I, Lewin M, Pellegrino MG, Einck L, Henriques HF, Simon GL, Parenti DM, Scheib RG, Schulof RS, Montefiori DC, Robinson WE, Mitchell WM, Volsky DJ, Paul D, Paxton H, Meyer III WA, Karikó K, Reichenbach N, Suhadolnik RJ, Gillespie DH (1987) Clinical, immunological, and virological effects of ampligen, a mismatched double-stranded RNA, in patients with AIDS or AIDS-related complex. Lancet i: 1286–1292.

    Article  Google Scholar 

  • Carter WA, Ventura D, Shapiro DE, Strayer DR, Gillespie DH, Hubbell HR (1991) Mismatched double-stranded RNA, ampligen (poly(I) poly(C12U)), demonstrates antiviral and immunostimulatory activities in HIV disease. Int J Immunopharmacol 13 (Suppl 1): 69–76.

    Article  PubMed  CAS  Google Scholar 

  • Castora FJ, Kelly WG (1986) ATP inhibits nuclear and mitochondrial type I topoisomerases from human leukemia cells. Proc Natl Acad Sci USA 83:1680–1684.

    Article  PubMed  CAS  Google Scholar 

  • Castora FJ, Erickson CE, Kovacs T, Lesiak K, Torrence PF (1991) 2′,5′-Oligoadenylate inhibits relaxation of supercoiled DNA by calf thymus DNA topoisomerase I. J Interferon Res 11:143–149.

    Article  PubMed  CAS  Google Scholar 

  • Cayley PJ, Davies JA, McCullagh KG, Kerr IM (1984) Activation of the ppp(A2′p)nA system in interferon-treated, herpes simplex virus-infected cells and evidence for novel inhibitors of the ppp(A2′p)nA-dependent RNase. Eur J Biochem 143:165–174.

    Article  PubMed  CAS  Google Scholar 

  • Charachon G, Sobol RW, Bisbal C, Salehzada T, Silhol M, Charubala R, Pfleiderer W, Lebleu B, Suhadolnik RJ (1990) Phosphorothioate analogues of (2′-5′)(A)4: agonist and antagonist activities in intact cells. Biochemistry 29:2550–2556.

    Article  PubMed  CAS  Google Scholar 

  • Chebath J, Benech P, Hovanessian A, Galabru J, Revel M (1987a) Four different forms of interferon-induced 2′,5′-oligo(A) synthetase identified by immunoblotting in human cells. J Biol Chem 262:3852–3857.

    PubMed  CAS  Google Scholar 

  • Chebath J, Benech P, Revel M, Vigneron M (1987b) Constitutive expression of (2′-5′) oligo A synthetase confers resistance to picomavirus infection. Nature 330:587–588.

    Article  PubMed  CAS  Google Scholar 

  • Cohen B, Peretz D, Vaiman D, Benech P, Chebath J (1988) Enhancer-like interferon responsive sequences of the human and murine (2′-5′)oligoadenylate synthetase gene promotors. EMBO J 7:1411–1419.

    PubMed  CAS  Google Scholar 

  • Cook PR (1989) The nucleoskeleton and the topology of transcription. Eur J Biochem 185:487–501.

    Article  PubMed  CAS  Google Scholar 

  • De Benedetti A, Pytel BA, Baglioni C (1987) Loss of (2′-5′)oligoadenylate synthetase activity by production of antisense RNA results in lack of protection by interferon from viral infections. Proc Natl Acad Sci USA 84:658–662.

    Article  PubMed  Google Scholar 

  • Dingwall C, Ernberg I, Gait MJ, Green SM, Heaphy S, Karn J, Lowe AD, Singh M, Skinner MA, Valerio R (1989) Human immunodeficiency virus-1 tat protein binds TAR RNA in vitro. Proc Natl Acad Sci USA 86:6925–6929.

    Article  PubMed  CAS  Google Scholar 

  • Doetsch PW, Suhadolnik RJ, Sawada Y, Mosca JD, Flick MB, Reichenbach NJ, Dang AQ, Wu JM, Charubala R, Pfleiderer W, Henderson EE (1981) Core (2′-5′)oligoadenylate and the cordycepin analog: inhibitors of Epstein-Barr virus-induced transformation of human lymphocytes in the absence of interferon. Proc Natl Acad Sci USA 78:6699–6703.

    Article  PubMed  CAS  Google Scholar 

  • Edery I, Petryshyn R, Sonenberg N (1989) Activation of double-stranded RNA-dependent kinase (dsl) by the TAR region of HIV-1 mRNA: a novel translational control mechanism. Cell 56:303–312.

    Article  PubMed  CAS  Google Scholar 

  • Faltynek CR, Princier GL, Ruscetti FW, Birchenall-Sparks M (1988) Lectins modulate the internal-ization of recombinant interferon-alpha A and the induction of 2′,5′-oligo(A) synthetase. J Biol Chem 263:7112–7117.

    PubMed  CAS  Google Scholar 

  • Farrell PJ, Balkow K, Hunt T, Jackson RJ, Trachsel H (1977) Phosphorylation of initiation factor eIF-2 and the control of reticulocyte protein synthesis. Cell 11:187–200.

    Article  PubMed  CAS  Google Scholar 

  • Fauci AS (1988) The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 239:617–622.

    Article  PubMed  CAS  Google Scholar 

  • Floyd-Smith G, Slattery E, Lengyel P (1981) Interferon action: RNA cleavage pattern of a (2′-5′)oligoadenylate-dependent endonuclease. Science 212:1030–1032.

    Article  PubMed  CAS  Google Scholar 

  • Frankel AD, Bredt DS, Pabo CO (1988) Tat protein from human immunodeficiency virus forms a metal-linked dimer. Science 240:70–73.

    Article  PubMed  CAS  Google Scholar 

  • Gatignol A, Kumar A, Rabson A, Jeang KT (1989) Identification of cellular proteins that bind to the human immunodeficiency virus type 1 trans-activation-responsive TAR element RNA. Proc Natl Acad Sci USA 86:7828–7832.

    Article  PubMed  CAS  Google Scholar 

  • Gaynor R, Soultanakis E, Kuwabara M, Garcia J, Sigman DS (1989) Specific binding of HeLa cell nuclear protein to RNA sequences in the human immunodeficiency virus transactivating region. Proc Natl Acad Sci USA 86:4845–4862.

    Article  Google Scholar 

  • Gendelman HE, Friedman RM, Joe S, Baca LM, Turpin JA, Dveksler G, Meltzer MS, Dieffenbach C (1990) A selective defect of interferon alpha production in human immunodeficiency virus-infected monocytes. J Exp Med 172:1433–1442.

    Article  PubMed  CAS  Google Scholar 

  • Gunnery S, Rice AP, Robertson HD, Mathews MB (1990) Tat-responsive region RNA of human immunodeficiency virus 1 can prevent activation of the double-stranded-RNA-activated protein kinase. Proc Natl Acad Sci USA 87:8687–8691.

    Article  PubMed  CAS  Google Scholar 

  • Ho DD, Hartshorn KL, Rota TR, Andrews CA, Kaplan JC, Schooley RT, Hirsch MS (1985) Recombinant human interferon alpha-A suppresses HTLV-III replication in vitro. Lancet i: 602–604.

    Article  Google Scholar 

  • Hovanessian AG, Svab J, Marie I, Robert N, Chamaret S, Laurent AG (1988) Characterization of 69-and 100-kDa forms of 2-5A-synthetase from interferon-treated human cells. J Biol Chem 263:4945–4949.

    PubMed  CAS  Google Scholar 

  • Hubbell HR, Sheetz PC, Iogal SS, Brodsky I, Kariko K, Li S-W, Suhadolnik RJ, Sobol RW (1991) Heterogeneous nuclear RNA from hairy cell leukemia patients activates 2′,5′-oligoadenylate synthetase. Anticancer Res 11:1927–1932.

    PubMed  CAS  Google Scholar 

  • Johnston MI, Hearl WG (1987) Purification and characterization of a 2′-phosphodiesterase from bovine spleen. J Biol Chem 262:8377–8382.

    PubMed  CAS  Google Scholar 

  • Jongstra-Bilen J, Ittel M-E, Niedergang C, Vosberg H-P, Mandel P (1983) DNA topoisomerase I from calf thymus is inhibited in vitro by poly(ADP-ribosylation). Eur J Biochem 136:391–396.

    Article  PubMed  CAS  Google Scholar 

  • Kariko K, Li SW, Sobol RW, Suhadolnik RJ, Charubala R, Pfleiderer W (1987a) Phosphorothioate analogues of 2′,5′-oligoadenylate. Activation of 2′,5′-oligoadenylate-dependent endoribonuclease by 2′,5′-phosphorothioate cores and 5′-monophosphates. Biochemistry 26:7136–7142.

    Article  PubMed  CAS  Google Scholar 

  • Kariko K, Li SW, Sobol RW, Suhadolnik L, Reichenbach NL, Suhadolnik RJ, Charubala R, Pfleiderer W (1987b) Phosphorothioate analogs of 2-5A: elucidation of the stereochemical course of the enzymes of the 2-5A synthetase/RNase L system. Nucleosides Nucleotides 6:173–184.

    Article  CAS  Google Scholar 

  • Kariko K, Sobol RW, Suhadolnik L, Li SW, Reichenbach NL, Suhadolnik RJ, Charubala R, Pfleiderer W (1987c) Phosphorothioate analogues of 2′,5′-oligoadenylate. Enzymatically synthesized 2′,5′-phosphorothioate dimer and trimer: unequivocal structural assignment and activation of 2′,5′-oligoadenylate-dependent endoribonuclease. Biochemistry 26:7127–7135.

    Article  PubMed  CAS  Google Scholar 

  • Karn J (1991) Control of human immunodeficiency virus replication by the tat, rev, nef and protease genes. Curr Opinion Immunol 3:526–536.

    Article  CAS  Google Scholar 

  • Kerr IM, Brown RE (1978) pppA2′p5′A2′p5′A: an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells. Proc Natl Acad Sci USA 75:256–260.

    Article  PubMed  CAS  Google Scholar 

  • Kohlstaedt LA, Wang J, Friedman JM, Rice PA, Steitz TA (1992) Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256:1783–1790.

    Article  PubMed  CAS  Google Scholar 

  • Laurent G St, Yoshie O, Floyd-Smith G, Samanta H, Sehgal PB (1983) Interferon action: two (2′-5′)(A)n synthetases specified by distinct mRNAs in Ehrlich ascites tumor cells treated with interferon. Cell 33:95–102.

    Article  Google Scholar 

  • Lengyel P (1982) Biochemistry of interferons and their actions. Annu Rev Biochem 51:251–282.

    Article  PubMed  CAS  Google Scholar 

  • Liu LF (1989) DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem 58:351–375.

    Article  PubMed  CAS  Google Scholar 

  • Mace K, Scif I, Anjard C, De Maeyer-Guignard J, Dodon MD, Gazzolo L, De Maeyer E (1991) Enhanced resistance to HIV-1 replication in U937 cells stably transfected with the human IFN-β gene behind an MHC promoter fragment. J Immunol 147:3553–3559.

    PubMed  CAS  Google Scholar 

  • Malim MH, Bühnlein S, Hauber J, Cullen BR (1989) Functional dissection of the HIV-1 Rev trans-aetivator — Derivation of a trans-dominant repressor of Rev function. Cell 58:205–214.

    Article  PubMed  CAS  Google Scholar 

  • Marié I, Hovanessian AG (1992) The 69-kDa 2-5A synthetase is composed of two homologous and adjacent functional domains. J Biol Chem 267:9933–9939.

    PubMed  Google Scholar 

  • Matthes E, Langen P, Brachwitz H, Schröder HC, Maidhof A, Weiler BE, Renneisen K, Müller WEG (1990) Alteration of DNA topoisomerase II activity during infection of H9 cells by human immunodeficiency virus type I in vitro: a target for potential therapeutic agents. Antiviral Res 13:273–286.

    Article  PubMed  CAS  Google Scholar 

  • Montefiori iDC, Mitchell WM (1987) Antiviral activity of mismatched double-stranded RNA against human immunodeficiency virus in vitro. Proc Natl Acad Sci USA 84:2985–2989.

    Article  PubMed  CAS  Google Scholar 

  • Montefiori DC, Sobol RW, Li SW, Reichenbach NL, Suhadolnik RJ, Charubala R, Pfleiderer W, Modliszewski A, Robinson WE, Mitchell WM (1989) Phosphorothioate and cordycepin analogues of 2′,5′-oligoadenylate: inhibition of human immunodeficiency virus type 1 reverse transcriptase and infection in vitro. Proc Natl Acad Sci USA 86:7191–7194.

    Article  PubMed  CAS  Google Scholar 

  • Müller WEG, Schröder HC, Zahn RK, Dose K (1980) Degradation of 2′,5′-linked oligoriboadenylates by 3′-exoribonuclease and 5′-nucleotidase. Hoppe-Seyler′s Z Physiol Chem 361:469–472.

    PubMed  Google Scholar 

  • Müller WEG, Wenger R, Reuter P, Renneisen K, Schröder HC (1989) Association of tat protein and viral mRNA with nuclear matrix from HIV-1 infected cells. Biochim Biophys Acta 1008:208–212.

    PubMed  Google Scholar 

  • Müller WEG, Matthes E, Reuter P, Wenger R, Friese K, Kuchino Y, Schröder HC (1990a) Effect of nonviable preparations from human immunodeficiency virus type 1 on nuclear matrix-associated DNA polymerase α and DNA topoisomerase II activities. J AIDS 3:1–10.

    Google Scholar 

  • Müller WEG, Okamoto T, Reuter P, Ugarkovic D, Schröder HC (1990b) Functional characterization of Tat protein from human immunodeficiency virus; evidence that Tat links viral RNAs to nuclear matrix. J Biol Chem 265:3803–3808.

    PubMed  Google Scholar 

  • Müller WEG, Weiler BE, Charubala R, Pfleiderer W, Leserman L, Sobol RW, Suhadolnik RJ, Schrüder HC (1991) Cordycepin analogues of 2′,5′-oligoadenylate inhibit human immunodeficiency virus infection via inhibition of reverse transcriptase. Biochemistry 30:2027–2033.

    Article  PubMed  Google Scholar 

  • Murray HW, Rutin BY, Masur H, Roberts R (1984) Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. N Engl J Med 310:883–889.

    Article  PubMed  CAS  Google Scholar 

  • Nilsen TW, Baglioni C (1979) Mechanism for discrimination between viral and host mRNA in interferon-treated cells. Proc Natl Acad Sci USA 76:2600–2604.

    Article  PubMed  CAS  Google Scholar 

  • Nilsen TW, Maroney PA, Baglioni C (1982a) Synthesis of (2′-5′)oligoadenylate and activation of an endoribonuclease in interferon-treated HeLa cells infected with reovirus. J Virol 42:1039–1045.

    PubMed  CAS  Google Scholar 

  • Nilsen TW, Maroney PA, Robertson HD, Baglioni C (1982b) Heterogeneous nuclear RNA promotes synthesis of (2′,5′)oligoadenylate and is cleaved by the (2′,5′)oligoadenylate-activated endoribonuclease. Mol Cell Biol 2:154–160.

    PubMed  CAS  Google Scholar 

  • Nilsen TW, Wood DL, Baglioni C (1982c) Presence of 2′,5′-oligo(A) and of enzymes that synthesize, bind, and degrade 2′,5′-oligo(A) in HeLa cell nuclei. J Biol Chem 257:1602–1605.

    PubMed  CAS  Google Scholar 

  • Pestka S, Langer JA, Zoon KC, Samuel CE (1987) Interferons and their actions. Annu Rev Biochem 56:727–777.

    Article  PubMed  CAS  Google Scholar 

  • Pfleiderer W, Charubala R (1987) Synthesis of P-thioadenylyl(2′-5′)adenosine and P-thioadenylyl(2′-S′J-P-thioadenylyl(2′-5′)adenosine. Nucleosides Nucleotides 6:513–516.

    Article  Google Scholar 

  • Pfeifer K, Merz H, Steffen R, Müller WEG, Trumm S, Schulz J, Eich E, Schrüder HC (1992) In-vitro anti-HIV activity of lignans. Differential inhibition of HIV-1 integrase reaction, topoisomerase activity and cellular microtubules. J Pharm Med 2:75–97.

    Google Scholar 

  • Pommier Y, Kerrigan D, Hartman KD, Glazer RI (1990) Phosphorylation of mammalian DNA topoisomerase I and activation by protein kinase C. J Biol Chem 265:9418–9422.

    PubMed  CAS  Google Scholar 

  • Priel E, Showalter SD, Roberts M, Oroszlan S, Segal S, Aboud M, Blair DG (1990) Topoisomerase I activity associated with human immunodeficiency virus (HIV) particles and equine infectious anemia virus core. EMBO J 9:4167–4172.

    PubMed  CAS  Google Scholar 

  • Priel E, Showalter SD, Blair DG (1991) Inhibition of human immunodeficiency virus (HIV-1) replication in vitro by nontoxic doses of camptothecin, a topoisomerase I inhibitor. AIDS Res Hum Retrovir 7:65–72.

    PubMed  CAS  Google Scholar 

  • Renneisen K, Leserman L, Matthes E, Schröder HC, Müller WEG (1990) Inhibition of expression of human immunodeficiency virus-1 in vitro by antibody-targeted liposomes containing antisense RNA to the env region. J Biol Chem 265:16337–16342.

    PubMed  CAS  Google Scholar 

  • Rice AP, Kerr SM, Roberts WK, Brown RE, Kerr IM (1985) Novel 2′,5′-oligoadenylates synthesized in interferon-treated, vaccinia virus-infected cells. J Virol 56:1041–1044.

    PubMed  CAS  Google Scholar 

  • Rosen CA (1991) Regulation of HIV gene expression by RNA-protein interactions. Trends Genet 7:9–14.

    Article  PubMed  CAS  Google Scholar 

  • Rosen CA, Pavlakis GN (1990) Tat and Rev: positive regulators of HIV gene expression. AIDS 4:499–509.

    Article  PubMed  CAS  Google Scholar 

  • Rossol S, Voth R, Laubenstein HP, Müller WEG, Schröder HC, Meyer zum Büschenfelde KH, Hess G (1989) Interferon production in patients infected with HIV-1. J Infect Dis 159:815–821.

    Article  PubMed  CAS  Google Scholar 

  • Roy S, Katze MG, Parkin NT, Edery I, Hovanessian AG, Sonenberg N (1990) Control of the interferon-induced 68-kilodalton protein kinase by the HIV-1 tat gene product. Science 247:1216–1219.

    Article  PubMed  CAS  Google Scholar 

  • Rutherford MN, Hannigan GE, Williams BRG (1988) Interferon-induced binding of nuclear factors to promoter elements of the 2-5A synthetase gene. EMBO J 7:751–759.

    PubMed  CAS  Google Scholar 

  • Sarver N, Cantin EM, Chang PS, Zaia JA, Ladne PA, Stephens DA, Rossi JJ (1990) Ribozymes as potential anti-HIV-1 therapeutic agents. Science 247:1222–1225.

    Article  PubMed  CAS  Google Scholar 

  • Sawai H, Imai J, Lesiak K, Johnston MI, Torrence PF (1983) Cordycepin analogues of 2-5A and its derivatives. Chemical synthesis and biological activity. J Biol Chem 258:1671–1677.

    PubMed  CAS  Google Scholar 

  • Schmidt A, Chernajovsky Y, Shulman L, Federman P, Berissi H, Revel M (1979) An interferon-induced phosphodiesterase degrading (2′-5′)oligoadenylate and the C-C-A terminus of tRNA. Proc Natl Acad Sci USA 76:4788–4792.

    Article  PubMed  CAS  Google Scholar 

  • Schrüder HC, Zahn RK, Dose K, Müller WEG (1980) Purification and characterization of a poly(A)-specific exoribonuclease from calf thymus. J Biol Chem 255:4535–4538.

    Google Scholar 

  • Schröder HC, Gosselin G, Imbach J-L, Müller WEG (1984) Influence of the xyloadenosine analogue of 2′,5′-oligoriboadenylate on poly(A)-specific, 2′,5′-oligoriboadenylate degrading 2′,3′-exoribonuclease and further enzymes involved in poly(A) ( + )mRNA metabolism. Mol Biol Rep 10:83–89.

    Article  PubMed  Google Scholar 

  • Schrüder HC, Bachmann M, Diehl-Seifert B, Müller WEG (1987a) Transport of mRNA from nucleus to cytoplasm. Prog Nucleic Acid Res Mol Biol 34:89–142.

    Article  Google Scholar 

  • Schröder HC, Trölltsch D, Friese U, Bachmann M, Müller WEG (1987b) Mature mRNA is selectively released from the nuclear matrix by an ATP/dATP-dependent mechanism sensitive to topoisomerase inhibitors. J Biol Chem 262:8917–8925.

    PubMed  Google Scholar 

  • Schröder HC, Wenger R, Rottmann M, Müller WEG (1988) Alteration of nuclear (2′-5′)oligo-riboadenylate synthetase and nuclease activities preceding replication of human immunodeficiency virus in H9 cells. Biol Chem Hoppe-Seyler 369:985–995.

    Article  PubMed  Google Scholar 

  • Schröder HC, Wenger R, Kuchino Y, Müller WEG (1989) Modulation of nuclear matrix-associated (2′-5′)oligoadenylate metabolism and ribonuclease L activity in H9 cells by human immunodeficiency virus. J Biol Chem 264:5669–5673.

    PubMed  Google Scholar 

  • Schröder HC, Kljajic Z, Weiler BE, Gasic M, Uhlenbruck G, Kurelec B, Müller WEG (1990a) The galactose-specific lectin from the sponge Chondrilla nucula displays anti-human immunodeficiency virus activity in vitro via stimulation of the (2′-5′)oligoadenylate metabolism. Antivir Chem Chemother 1:99–105.

    Google Scholar 

  • Schrüder HC, Merz H, Steffen R, Müller WEG, Sarin PS, Trumm S, Schulz J, Eich E (1990b) Differential in vitro anti-HIV activity of natural lignans. Z Naturforsch 45c: 1215–1221.

    Google Scholar 

  • Schröder HC, Ugarkovic D, Merz H, Kuchino Y, Okamoto T, Müller WEG (1990c) Protection of HeLa-T4+ cells against human immunodeficiency virus (HIV) infection after stable transfection with HIV LTR — 2′,5′-oligoadenylate synthetase hybrid gene. FASEB J 4:3124–3130.

    PubMed  Google Scholar 

  • Schröder HC, Ugarkovic D, Wenger R, Merz H, Müller WEG (1990d) Suppression of HIV-1 replication by a HIV-traws-activated enzyme of the cellular antiviral response. AIFO 5: 533–534.

    Google Scholar 

  • Schröder HC, Ugarkovic D, Wenger R, Okamoto T, Müller WEG (1990e) Binding of Tat protein to TAR region of human immunodeficiency virus type 1 blocks TAR-mediated activation of (2′-5′)oligoadenylate synthetase. AIDS Res Hum Retrovir 6:659–672.

    Article  PubMed  Google Scholar 

  • Schröder HC, Suhadolnik RJ, Pfleiderer W, Charubala R, Müller WEG (1992) (2′-5′)Oligoadenylate and intracellular immunity against retrovirus infection. Int J Biochem 24:55–63.

    Article  PubMed  Google Scholar 

  • Schröder HC, Kelve M, Schäcke H, Pfleiderer W, Charubala R, Suhadolnik RJ, Müller WEG (1993) Inhibition of DNA topoisomerase I activity by 2′,5′-oligoadenylates and mismatched double-stranded RNA (ampligen) in uninfected and HIV-1-infected H9 cells. Chem-Biol Interactions (in press).

    Google Scholar 

  • Schulof RS, Scheib RG, Parenti DM, Simon GL, DiGioia RA, Paxton HM, Chandra P, Courtless C, Taguchi TY, Sun KD, Goldstein IA, Sarin PS (1986) Treatment of HTLV-III/LAV patients with D-penicillamine. Arzneim Forsch (Drug Research) 36:1531–1534.

    CAS  Google Scholar 

  • Sen GC (1982) Mechanism of interferon action: progress towards its understanding. Prog Nucleic Acid Res Mol Biol 27:105–156.

    Article  PubMed  CAS  Google Scholar 

  • SenGupta DN, Silverman RH (1989) Activation of interferon-regulated, dsRNA-dependent enzymes by human immunodeficiency virus-1 leader RNA. Nucleic Acids Res 17:969–978.

    Article  PubMed  CAS  Google Scholar 

  • SenGupta DN, Berkhout B, Gatignol A, Zhou A, Silverman RH (1990) Direct evidence for translational regulation by leader RNA and Tat protein of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 87:7492–7496.

    Article  PubMed  CAS  Google Scholar 

  • Shuman S, Moss B (1987) Identification of a vaccinia virus gene encoding a type I DNA topoisomerase. Proc Natl Acad Sci USA 84:7478–7482.

    Article  PubMed  CAS  Google Scholar 

  • Silverman RH, Jung DD, Nolan-Sorden NL, Dieffenbach CW, Kedar VP, SenGupta DN (1988) Purification and analysis of murine 2-5A-dependent RNase. J Biol Chem 263:7336–7341.

    PubMed  CAS  Google Scholar 

  • Skidmore SJ, Mawson SJ (1987) Alpha-interferon in anti-HIV positive patients. Lancet ii:520.

    Article  Google Scholar 

  • Smekens M, Dumont JE, Degeyter A, Galand P (1986) Effect of estrogen administration on rat liver 2-5A synthetase activity. Biochim Biophys Acta 887:341–344.

    Article  PubMed  CAS  Google Scholar 

  • Sobol RW, Suhadolnik RJ, Kumar A, Lee BJ, Hatfield DL, Wilson SH (1991) Localization of a polynucleotide binding region in the HIV-1 reverse transcriptase: implications for primer binding. Biochemistry 30:10623–10631.

    Article  PubMed  CAS  Google Scholar 

  • Strayer DR, Carter WA, Pequignot E, Topolsky D, Brodsky I, Suhadolnik RJ, Reichenbach N, Paul D, Einck L, Hubbell ER, Pinto A, Strauss K, Gillespie D (1991) Activity of synthetic dsRNA — ampligen — in HIV disease. Clin Biotechnol 3:169–175.

    Google Scholar 

  • Suhadolnik RJ, Doetsch PW, Devash Y, Henderson EE, Charubala R, Pfleiderer W (1983) 2′,5′-Adenylate and cordycepin trimer cores: metabolic stability and evidence for antimitogenesis without 5′-rephosphorylation. Nucleosides Nucleotides 2:351–366.

    Article  CAS  Google Scholar 

  • Suhadolnik RJ, Lebleu B, Pfleiderer W, Charubala R, Montefiori DC, Mitchell WM, Sobol RW, Li SW, Kariko K, Reichenbach NL (1989) Phosphorothioate analogs of 2-5A: activation/inhibition of RNase L and inhibition of HIV-1 reverse transcriptase. Nucleosides Nucleotides 8:987–990.

    Article  Google Scholar 

  • Sullenger BA, Gallardo HF, Ungers GE, Gilboa E (1990) Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication. Cell 63:601–608.

    Article  PubMed  CAS  Google Scholar 

  • Trask DK, DiDonato JA, Muller MT (1984) Rapid detection and isolation of covalent DNA/protein complexes: application to topoisomerase I and II. EMBO J 3:671–676.

    PubMed  CAS  Google Scholar 

  • Trono D, Feinberg MB, Baltimore D (1989) HIV-1 gag mutants can dominantly interfere with the replication of the wild-type virus. Cell 59:113–120.

    Article  PubMed  CAS  Google Scholar 

  • Ushijima H, Rytik PG, Schäcke H, Scheffer U, Müller WEG, Schröder HC (1993) Mode of action of the anti-AIDS compound poly(I) poly(C12U) (ampligen): activator of 2′,5′-oligoadenylate synthetase and double-stranded RNA-dependent kinase. J Interferon Res 13:161–171.

    Article  PubMed  CAS  Google Scholar 

  • Verheijen R, van Venrooij W, Ramaekers F (1988) The nuclear matrix: structure and composition. J Cell Sci 90:11–36.

    PubMed  Google Scholar 

  • Voth R, Rossol S, Hess G, Schütt KH, Schröder HC, Meyer zum Büschenfelde K-H, Müller WEG (1990) Differential gene expression of interferon-alpha and tumor necrosis factor-alpha in peripheral blood mononuclear cells from patients with AIDS related complex and AIDS. J Immunol 144:970–975.

    PubMed  CAS  Google Scholar 

  • Wang JC (1985) DNA topoisomerases. Annu Rev Biochem 54:665–697.

    Article  PubMed  CAS  Google Scholar 

  • Weis JH, Faras AJ (1981) DNA topoisomerase activity associated with Rous sarcoma virus. Virology 114:563–566.

    Article  PubMed  CAS  Google Scholar 

  • Wells V, Mallucci L (1985) Expression of the 2-5A system during the cell cycle. Exp Cell Res 159:27–36.

    Article  PubMed  CAS  Google Scholar 

  • Wong-Staal F, Gallo RC (1985) Human T-lymphotropic retroviruses. Nature 317:395–403.

    Article  PubMed  CAS  Google Scholar 

  • Wreschner DH, McCauley JW, Skehel JJ, Kerr IM (1981) Interferon action — sequence specificity of the ppp(A2′p)nA-dependent ribonuclease. Nature 289:414–417.

    Article  PubMed  CAS  Google Scholar 

  • Wu FK, Garcia JA, Harrich D, Gaynor RB (1988) Purification of the human immunodeficiency virus type 1 enhancer and TAR binding proteins EBP-1 and UBP-1. EMBO J 7:2117–2129.

    PubMed  CAS  Google Scholar 

  • Yang K, Samanta H, Dougherty T, Jayaram B, Broeze R, Lengyel P (1981) Interferons, double-stranded RNA, and RNA degradation. Isolation and characterization of homogeneous human (2′-5′)(A)n synthetase. J Biol Chem 256:9324–9328.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Johannes Gutenberg-Universität, Duesbergweg 6, D-55099, Mainz, Germany

    H. C. Schröder & W. E. G. Müller

  2. Institute of Chemical Physics and Biophysics, Akadeemia tee 23, EE0026, Tallinn, Estonia

    M. Kelve

Authors
  1. H. C. Schröder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Kelve
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. E. G. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institut für Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universität Mainz, Duesbergweg 6, 55099, Mainz, Germany

    W. E. G. Müller  & H. C. Schröder  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Schröder, H.C., Kelve, M., Müller, W.E.G. (1994). The 2-5A System and HIV Infection. In: Müller, W.E.G., Schröder, H.C. (eds) Biological Response Modifiers — Interferons, Double-Stranded RNA and 2′,5′-Oligoadenylates. Progress in Molecular and Subcellular Biology, vol 14. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78549-8_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-78549-8_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-78551-1

  • Online ISBN: 978-3-642-78549-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation