HIV-1 inactivation by nucleic acid aptamers.
Although developments in small-molecule therapeutics for HIV-1 have been dramatic in recent years, the rapid selection of drug-resistant viral strains and the adverse side effects associated with long-term exposure to current treatments propel continued exploration of alternative anti-HIV-1 agents. Non-coding nucleic acids have emerged as potent inhibitors that dramatically suppress viral function both in vitro and in cell culture. In particular, RNA and DNA aptamers inhibit HIV-1 function by directly interfering with essential proteins at critical stages in the viral replication cycle (Figure 1). Their antiviral efficacy is expected to be a function, in part, of the biochemical properties of the aptamer-target interaction. Accordingly, we present an overview of biochemical and cell culture analyses of the expanding list of aptamers targeting HIV-1. Our discussion focuses on the inhibition of viral enzymes (reverse transcription, proteolytic processing, and chromosomal integration), viral expression (Rev/RRE and Tat/TAR), viral packaging (p55Gag, matrix and nucleocapsid), and viral entry (gp120) (Table 1). Additional nucleic acid-based strategies for inactivation of HIV-1 function (including RNAi, antisense, and ribozymes) have also demonstrated their utility. These approaches are reviewed in other chapters of this volume and elsewhere.
Held
Daniel M
DM
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Kissel
Jay D
JD
Patterson
James T
JT
Nickens
David G
DG
Burke
Donald H
DH
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000821:virology; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry; D001483:Base Sequence; D004277:DNA, Single-Stranded / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D015683:Gene Products, gag / Q000378:metabolism; D015694:Gene Products, rev / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism; D015752:Genes, env; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D019427:HIV Integrase / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009696:Nucleic Acids / Q000737:chemistry*; D019251:Nucleocapsid; D010447:Peptide Hydrolases / Q000737:chemistry; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism; D019065:Virus Assembly; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D004277:DNA, Single-Stranded; D015683:Gene Products, gag; D015694:Gene Products, rev; D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D009696:Nucleic Acids; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D019427:HIV Integrase; D054303:HIV Reverse Transcriptase; D010447:Peptide Hydrolases