Top

Published in:

01-10-2009 | Review Article

Progress towards Therapeutic Application of RNA Interference for HIV Infection

Authors: Sunit K. Singh, Dr Rajesh K. Gaur

Published in: BioDrugs | Issue 5/2009

Abstract

HIV-1 infection is the cause of acquired immune deficiency syndrome (AIDS). Highly active anti-retroviral therapy (HAART) has been successful in reducing the rate of progression to AIDS, but a cure has not yet been achieved. New tools are required to delay progression of infection or to block the replication cycle of HIV. RNA interference (RNAi) has the potential to work as a powerful tool against HIV infection. The mode of action of small interfering RNAs (siRNAs) against their target genes is through sequence complementarity, which in turn results in target degradation. siRNAs are showing enormous potential to be used as a therapeutic tool in various diseases; however, this technology still requires refinement before its full potential can be utilized for the development of HIV therapies.

Finzi D, Blankson J, Siliciano JD, et al. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 1999 May; 5(5): 512–7PubMedCrossRef

Saag MS, Kilby JM. HIV-1 and HAART: a time to cure, a time to kill. Nat Med 1999 Jun; 5(6): 609–11PubMedCrossRef

Voss G, Villinger F. Adjuvanted vaccine strategies and live vector approaches for the prevention of AIDS. AIDS 2000; 14Suppl. 3: S153–65PubMed

Reyes-Darias JA, Sanchez-Luque FJ, Berzal-Herranz A. Inhibition of HIV-1 replication by RNA-based strategies. Curr HIV Res 2008 Nov; 6(6): 500–14PubMedCrossRef

Scherer L, Rossi JJ, Weinberg MS. Progress and prospects: RNA-based therapies for treatment of HIV infection. Gene Ther 2007 Jul; 14(14): 1057–64PubMedCrossRef

Morris KV, Rossi JJ. Lentivirus-mediated RNA interference therapy for human immunodeficiency virus type 1 infection. Hum Gene Ther 2006 May; 17(5): 479–86PubMedCrossRef

Rossi JJ. Expression strategies for short hairpin RNA interference triggers. Hum Gene Ther 2008 Apr; 19(4): 313–7PubMedCrossRef

van Rij RP, Andino R. The silent treatment: RNAi as a defense against virus infection in mammals. Trends Biotechnol 2006 Apr; 24(4): 186–93PubMedCrossRef

Zhu P, Winkler H, Chertova E, et al. 2008 Cryoelectron tomography of HIV-1 envelope spikes: further evidence for tripod-like legs. PLoS Pathog 2008 Nov; 4(11): e1000203PubMedCrossRef

10.

Sougrat R, Bartesaghi A, Lifson JD, et al. 2008 Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry. PLoS Pathog 2007 May 4; 3(5): e63PubMedCrossRef

11.

Dalgleish AG, Beverley PC, Clapham PR, et al. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984 Dec 20–1985 Jan 2; 312(5996): 763–7PubMedCrossRef

12.

Klatzmann D, Champagne E, Chamaret S, et al. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 1984 Dec 20–1985 Jan 2; 312(5996): 767–8PubMedCrossRef

13.

Bour S, Geleziunas R, Wainberg MA. The human immunodeficiency virus type 1 (HIV-1) CD4 receptor and its central role in promotion of HIV-1 infection. Microbiol Rev 1995 Mar; 59(1): 63–93PubMed

14.

Deng H, Liu R, Ellmeier W, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 1996 Jun 20; 381(6584): 661–6PubMedCrossRef

15.

Doranz BJ, Rucker J, Yi Y, et al. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 1996 Jun 28; 85(7): 1149–58PubMedCrossRef

16.

Feng Y, Broder CC, Kennedy PE, et al. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996 May 10; 272(5263): 872–7PubMedCrossRef

17.

Deng HK, Unutmaz D, KewalRamani VN, et al. Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature 1997 Jul 17; 388(6639): 296–300PubMedCrossRef

18.

Liao F, Alkhatib G, Peden KW, et al. STRL33, a novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1. J Exp Med 1997 Jun 2; 185(11): 2015–23PubMedCrossRef

19.

Cocchi F, DeVico AL, Garzino-Demo A, et al. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 1995 Dec 15; 270(5243): 1811–5PubMedCrossRef

20.

Wang QC, Nie QH, Feng ZH. RNA interference: antiviral weapon and beyond. World J Gastroenterol 2003 Aug; 9(8): 1657–61PubMed

21.

Song E, Zhu P, Lee SK, et al. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol 2005 Jun; 23(6): 709–17PubMedCrossRef

22.

Lee SK, Dykxhoorn DM, Kumar P, et al. Lentiviral delivery of short hairpin RNAs protects CD4 T cells from multiple clades and primary isolates of HIV. Blood 2005 Aug 1; 106(3): 818–26PubMedCrossRef

23.

Chang LJ, Liu X, He J. Lentiviral siRNAs targeting multiple highly conserved RNA sequences of human immunodeficiency virus type 1. Gene Ther 2005 Jul; 12(14): 1133–44PubMedCrossRef

24.

Hu WY, Myers CP, Kilzer JM, et al. Inhibition of retroviral pathogenesis by RNA interference. Curr Biol 2002 Aug 6; 12(15): 1301–11PubMedCrossRef

25.

Barnor JS, Miyano-Kurosaki N, Yamaguchi K, et al. Lentiviral-mediated delivery of combined HIV-1 decoy TAR and Vif siRNA as a single RNA molecule that cleaves to inhibit HIV-1 in transduced cells. Nucleosides Nucleotides Nucleic Acids 2005; 24(5–7): 431–4PubMedCrossRef

26.

Coburn GA, Cullen BR. Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference. J Virol 2002 Sep; 76(18): 9225–31PubMedCrossRef

27.

Lee MT, Coburn GA, McClure MO, et al. Inhibition of human immunodeficiency virus type 1 replication in primary macrophages by using Tat- or CCR5-specific small interfering RNAs expressed from a lentivirus vector. J Virol 2003 Nov; 77(22): 11964–72PubMedCrossRef

28.

Dave RS, Pomerantz RJ. Antiviral effects of human immunodeficiency virus type 1-specific small interfering RNAs against targets conserved in select neurotropic viral strains. J Virol 2004 Dec; 78(24): 13687–96PubMedCrossRef

29.

Li MJ, Kim J, Li S, et al. Long-term inhibition of HIV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme, and a nucleolar-localizing TAR decoy. Mol Ther 2005 Nov; 12(5): 900–9PubMedCrossRef

30.

Park J, Nadeau P, Zucali JR, et al. Inhibition of simian immunodeficiency virus by foamy virus vectors expressing siRNAs. Virology 2005 Dec 20; 343(2): 275–82PubMedCrossRef

31.

Park WS, Hayafune M, Miyano-Kurosaki N, et al. Specific HIV-1 env gene silencing by small interfering RNAs in human peripheral blood mononuclear cells. Gene Ther 2003 Nov; 10(24): 2046–50PubMedCrossRef

32.

Puerta-Fernandez E, Barroso-del Jesus A, Romero-Lopez C, et al. Inhibition of HIV-1 replication by RNA targeted against the LTR region. AIDS 2005 Jun 10; 19(9): 863–70PubMedCrossRef

33.

Novina CD, Murray MF, Dykxhoorn DM, et al. siRNA-directed inhibition of HIV-1 infection. Nat Med 2002 Jul; 8(7): 681–6PubMed

34.

Park WS, Miyano-Kurosaki N, Hayafune M, et al. Prevention of HIV-1 infection in human peripheral blood mononuclear cells by specific RNA interference. Nucleic Acids Res 2002 Nov 15; 30(22): 4830–5PubMedCrossRef

35.

Kitabwalla M, Ruprecht RM. RNA interference: a new weapon against HIV and beyond. N Engl J Med 2002 Oct 24; 347(17): 1364–7PubMedCrossRef

36.

Martinez MA, Gutierrez A, Armand-Ugon M, et al. Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication. AIDS 2002 Dec 6; 16(18): 2385–90PubMedCrossRef

37.

Qin XF, An DS, Chen IS, et al. Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci U S A 2003 Jan 7; 100(1): 183–8PubMedCrossRef

38.

Moore JP. Coreceptors: implications for HIV pathogenesis and therapy. Science 1997 Apr 4; 276(5309): 51–2PubMedCrossRef

39.

Nibbs RJ, Kriehuber E, Ponath PD, et al. The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors. Am J Pathol 2001 Mar; 158(3): 867–77PubMedCrossRef

40.

Neil SJ, Aasa-Chapman MM, Clapham PR, et al. The promiscuous CC chemokine receptor D6 is a functional coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and HIV-2 on astrocytes. J Virol 2005 Aug; 79(15): 9618–24PubMedCrossRef

41.

Jacque JM, Triques K, Stevenson M. Modulation of HIV-1 replication by RNA interference. Nature 2002 Jul 25; 418(6896): 435–8PubMedCrossRef

42.

Capodici J, Kariko K, Weissman D. Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J Immunol 2002 Nov 1; 169(9): 5196–201PubMed

43.

Nishitsuji H, Ikeda T, Miyoshi H, et al. Expression of small hairpin RNA by lentivirus-based vector confers efficient and stable gene-suppression of HIV-1 on human cells including primary non-dividing cells. Microbes Infect 2004 Jan; 6(1): 76–85PubMedCrossRef

44.

Surabhi RM, Gaynor RB. RNA interference directed against viral and cellular targets inhibits human immunodeficiency virus type 1 replication. J Virol 2002 Dec; 76(24): 12963–73PubMedCrossRef

45.

Westerhout EM, ter Brake O, Berkhout B. The virion-associated incoming HIV-1 RNA genome is not targeted by RNA interference. Retrovirology 2006; 3: 57PubMedCrossRef

46.

Li CJ. Therapeutic biology: checkpoint pathway activation therapy, HIV Tat, and transkingdom RNA interference. J Cell Physiol 2006 Dec; 209(3): 695–700PubMedCrossRef

47.

Komano J, Miyauchi K, Matsuda Z, et al. Inhibiting the Arp2/3 complex limits infection of both intracellular mature vaccinia virus and primate lentiviruses. Mol Biol Cell 2004 Dec; 15(12): 5197–207PubMedCrossRef

48.

Kameoka M, Nukuzuma S, Itaya A, et al. RNA interference directed against Poly(ADP-Ribose) polymerase 1 efficiently suppresses human immunodeficiency virus type 1 replication in human cells. J Virol 2004 Aug; 78(16): 8931–4PubMedCrossRef

49.

Chiu YL, Cao H, Jacque JM, et al. Inhibition of human immunodeficiency virus type 1 replication by RNA interference directed against human transcription elongation factor P-TEFb (CDK9/CyclinT1). J Virol 2004 Mar; 78(5): 2517–29PubMedCrossRef

50.

Price DH. P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II. Mol Cell Biol 2000 Apr; 20(8): 2629–34PubMedCrossRef

51.

Garrus JE, von Schwedler UK, Pornillos OW, et al. Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 2001 Oct 5; 107(1): 55–65PubMedCrossRef

52.

Stevenson M. Dissecting HIV-1 through RNA interference. Nat Rev Immunol 2003 Nov; 3(11): 851–8PubMedCrossRef

53.

Yu Z, Sanchez-Velar N, Catrina IE, et al. The cellular HIV-1 Rev cofactor hRIP is required for viral replication. Proc Natl Acad Sci U S A 2005 Mar 15; 102(11): 4027–32PubMedCrossRef

54.

Modem S, Badri KR, Holland TC, et al. Sam68 is absolutely required for Rev function and HIV-1 production. Nucleic Acids Res 2005; 33(3): 873–9PubMedCrossRef

55.

Liu S, Asparuhova M, Brondani V, et al. Inhibition of HIV-1 multiplication by antisense U7 snRNAs and siRNAs targeting cyclophilin A. Nucleic Acids Res 2004; 32(12): 3752–9PubMedCrossRef

56.

Thomas CE, Ehrhardt A, Kay MA. Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet 2003 May; 4(5): 346–58PubMedCrossRef

57.

Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells. Science 2002 Apr 19; 296(5567): 550–3PubMedCrossRef

58.

Paddison PJ, Caudy AA, Bernstein E, et al. Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev 2002 Apr 15; 16(8): 948–58PubMedCrossRef

59.

Morrissey DV, Lockridge JA, Shaw L, et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 2005 Aug; 23(8): 1002–7PubMedCrossRef

60.

Soutschek J, Akinc A, Bramlage B, et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 2004 Nov 11; 432(7014): 173–8PubMedCrossRef

61.

Zimmermann TS, Lee AC, Akinc A, et al. RNAi-mediated gene silencing in non-human primates. Nature 2006 May 4; 441(7089): 111–4PubMedCrossRef

62.

Kim DH, Rossi JJ. Strategies for silencing human disease using RNA interference. Nat Rev Genet 2007 Mar; 8(3): 173–84PubMedCrossRef

63.

McNamara II JO, Andrechek ER, Wang Y, et al. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 2006 Aug; 24(8): 1005–15PubMedCrossRef

64.

Hu-Lieskovan S, Heidel JD, Bartlett DW, et al. Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma. Cancer Res 2005 Oct 1; 65(19): 8984–92PubMedCrossRef

65.

Zhou J, Swiderski P, Li H, et al. Selection, characterization and application of new RNA HIV gp 120 aptamers for facile delivery of Dicer substrate siRNAs into HIV infected cells. Nucleic Acids Res 2009; 37(9): 3094–109PubMedCrossRef

66.

Anderson J, Banerjea A, Akkina R. Bispecific short hairpin siRNA constructs targeted to CD4, CXCR4, and CCR5 confer HIV-1 resistance. Oligonucleotides 2003; 13(5): 303–12PubMedCrossRef

67.

Anderson J, Akkina R. HIV-1 resistance conferred by siRNA cosuppression of CXCR4 and CCR5 coreceptors by a bispecific lentiviral vector. AIDS Res Ther 2005 Jan 13; 2(1): 1PubMedCrossRef

68.

Anderson J, Akkina R. CXCR4 and CCR5 shRNA transgenic CD34+ cell derived macrophages are functionally normal and resist HIV-1 infection. Retrovirology 2005; 2: 53PubMedCrossRef

69.

Kumar P, Ban HS, Kim SS, et al. T cell-specific siRNA delivery suppresses HIV-1 infection in humanized mice. Cell 2008 Aug 22; 134(4): 577–86PubMedCrossRef

70.

Gitlin L, Karelsky S, Andino R. Short interfering RNA confers intracellular antiviral immunity in human cells. Nature 2002 Jul 25; 418(6896): 430–4PubMedCrossRef

71.

Michienzi A, Castanotto D, Lee N, et al. RNA-mediated inhibition of HIV in a gene therapy setting. Ann N Y Acad Sci 2003 Dec; 1002: 63–71PubMedCrossRef

72.

Singh SK. RNA interference and its therapeutic potential against HIV infection. Expert Opin Biol Ther 2008 Apr; 8(4): 449–61PubMedCrossRef

73.

Bennasser Y, Le SY, Benkirane M, et al. Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing. Immunity 2005 May; 22(5): 607–19PubMedCrossRef

74.

Williams BR. PKR: a sentinel kinase for cellular stress. Oncogene 1999 Nov 1; 18(45): 6112–20PubMedCrossRef

75.

Nekhai S, Jerebtsova M. Therapies for HIV with RNAi. Curr Opin Mol Ther 2006 Feb; 8(1): 52–61PubMed

76.

Haasnoot J, de Vries W, Geutjes EJ, et al. The Ebola virus VP35 protein is a suppressor of RNA silencing. PLoS Pathog 2007 Jun; 3(6): e86PubMedCrossRef

77.

Li WX, Li H, Lu R, et al. Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing. Proc Natl Acad Sci U S A 2004 Feb 3; 101(5): 1350–5PubMedCrossRef

78.

Xu N, Segerman B, Zhou X, et al. Adenovirus virus-associated RNAII-derived small RNAs are efficiently incorporated into the RNA-induced silencing complex and associate with polyribosomes. J Virol 2007 Oct; 81(19): 10540–9PubMedCrossRef

79.

Boden D, Pusch O, Lee F, et al. Human immunodeficiency virus type 1 escape from RNA interference. J Virol 2003 Nov; 77(21): 11531–5PubMedCrossRef

80.

Das AT, Brummelkamp TR, Westerhout EM, et al. Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition. J Virol 2004 Mar; 78(5): 2601–5PubMedCrossRef

81.

Jackson AL, Burchard J, Schelter J, et al. Widespread siRNA ‘off-target’ transcript silencing mediated by seed region sequence complementarity. RNA 2006 Jul; 12(7): 1179–87PubMedCrossRef

82.

Birmingham A, Anderson EM, Reynolds A, et al. 3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets. Nat Methods 2006 Mar; 3(3): 199–204PubMedCrossRef

83.

Manche L, Green SR, Schmedt C, et al. Interactions between double-stranded RNA regulators and the protein kinase DAI. Mol Cell Biol 1992 Nov; 12(11): 5238–48PubMed

84.

Singh SK, Girschick HJ. Toll-like receptors in Borrelia burgdorferi-induced inflammation. Clin Microbiol Infect 2006 Aug; 12(8): 705–17PubMed

85.

Hornung V, Guenthner-Biller M, Bourquin C, et al. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat Med 2005 Mar; 11(3): 263–70PubMedCrossRef

86.

Kim DH, Longo M, Han Y, et al. Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase. Nat Biotechnol 2004 Mar; 22(3): 321–5PubMedCrossRef

87.

Marques JT, Devosse T, Wang D, et al. A structural basis for discriminating between self and nonself double-stranded RNAs in mammalian cells. Nat Biotechnol 2006 May; 24(5): 559–65PubMedCrossRef

88.

Robbins MA, Li M, Leung I, et al. Stable expression of shRNAs in human CD34+ progenitor cells can avoid induction of interferon responses to siRNAs in vitro. Nat Biotechnol 2006 May; 24(5): 566–71PubMedCrossRef

89.

Grimm D, Streetz KL, Jopling CL, et al. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature 2006 May 25; 441(7092): 537–41PubMedCrossRef

90.

An DS, Qin FX, Auyeung VC, et al. Optimization and functional effects of stable short hairpin RNA expression in primary human lymphocytes via lentiviral vectors. Mol Ther 2006 Oct; 14(4): 494–504PubMedCrossRef

Title: Progress towards Therapeutic Application of RNA Interference for HIV Infection
Authors: Sunit K. Singh
Dr Rajesh K. Gaur
Publication date: 01-10-2009
Publisher: Springer International Publishing
Published in: BioDrugs / Issue 5/2009
Print ISSN: 1173-8804
Electronic ISSN: 1179-190X
DOI: https://doi.org/10.2165/11317120-000000000-00000

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Progress towards Therapeutic Application of RNA Interference for HIV Infection

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2009

RNA Interference Technologies and Therapeutics

Recombinant Human Thrombin

Therapeutic Breast Cancer Vaccines

Monoclonal Antibodies Targeting Vascular Endothelial Growth Factor