HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, Y. Articles by Rosenblatt, J. D. Search for Related Content PubMed PubMed Citation Articles by Lu, Y. Articles by Rosenblatt, J. D. Social Bookmarking                      What's this?

Volume 272, Number 23, Issue of June 6, 1997 pp. 14523-14531
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Inhibition of HIV-1 Replication Using a Mutated tRNA^Lys-3 Primer

(Received for publication, September 19, 1996, and in revised form, February 25, 1997)

Yuanan Lu , Vicente Planelles ^§¶¶¶ , Xinqiang Li , Chockalingam Palaniappan ^§** , Brian Day ^§ , Pia Challita-Eid ^§¶¶ , Rafael Amado , Dennis Stephens , Donald B. Kohn , Andreas Bakker , Philip Fay ^§** , Robert A. Bambara ^§**¶ and Joseph D. Rosenblatt ^¶¶¶

From the  UCLA Department of Medicine, Division of Hematology-Oncology, UCLA AIDS Institute, Los Angeles, California 90095, the  Children's Hospital Los Angeles, University of Southern California School of Medicine, Los Angeles, California 90027, and the ^¶¶ University of Rochester Cancer Center and Departments of ^§ Medicine, ^¶ Microbiology, ^¶ Immunology, and ^** Biochemistry, University of Rochester, Rochester, New York 14642

Cellular tRNA^Lys-3 serves as the primer for reverse transcription of human immunodeficiency virus, type 1 (HIV-1). tRNA^Lys-3 interacts directly with HIV-1 reverse transcriptase, is packaged into viral particles and anneals to the primer-binding site (PBS) of the HIV-1 genome to initiate reverse transcription. Therefore, the priming step of reverse transcription is a potential target for antiviral strategies. We have developed a mutant tRNA^Lys-3 derivative with mutations in the PBS-binding region such that priming specificity was re-directed to the highly conserved TAR stem-loop region. This mutant tRNA retains high-affinity binding to HIV-1 reverse transcriptase, viral encapsidation, and is able to prime at both the targeted TAR sequence and at the viral PBS. Constitutive expression of mutant tRNA in T-cells results in marked inhibition of HIV-1 replication, as determined by measurements of viral infectivity, syncytium formation, and p24 production. Inhibition of retroviral replication through interference with the normal process of priming constitutes a new anti-retroviral approach and also provides a novel tool for dissecting molecular aspects of priming.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. Joshi and V. R. Prasad Potent Inhibition of Human Immunodeficiency Virus Type 1 Replication by Template Analog Reverse Transcriptase Inhibitors Derived by SELEX (Systematic Evolution of Ligands by Exponential Enrichment) J. Virol., June 5, 2002; 76(13): 6545 - 6557. [Abstract] [Full Text] [PDF]

				T. S. Fisher, P. Joshi, and V. R. Prasad Mutations That Confer Resistance to Template-Analog Inhibitors of Human Immunodeficiency Virus (HIV) Type 1 Reverse Transcriptase Lead to Severe Defects in HIV Replication J. Virol., March 19, 2002; 76(8): 4068 - 4072. [Abstract] [Full Text] [PDF]

				M. J. Renda, J. D. Rosenblatt, E. Klimatcheva, L. M. Demeter, R. A. Bambara, and V. Planelles Mutation of the Methylated tRNA3Lys Residue A58 Disrupts Reverse Transcription and Inhibits Replication of Human Immunodeficiency Virus Type 1 J. Virol., October 15, 2001; 75(20): 9671 - 9678. [Abstract] [Full Text] [PDF]

				M. Kameoka, L. Rong, M. Götte, C. Liang, R. S. Russell, and M. A. Wainberg Role for Human Immunodeficiency Virus Type 1 Tat Protein in Suppression of Viral Reverse Transcriptase Activity during Late Stages of Viral Replication J. Virol., March 15, 2001; 75(6): 2675 - 2683. [Abstract] [Full Text]

				X. Wei, M. Gotte, and M. A. Wainberg Human immunodeficiency virus type-1 reverse transcription can be inhibited in vitro by oligonucleotides that target both natural and synthetic tRNA primers Nucleic Acids Res., August 15, 2000; 28(16): 3065 - 3074. [Abstract] [Full Text] [PDF]

				P. Gerondelis, R. H. Archer, C. Palaniappan, R. C. Reichman, P. J. Fay, R. A. Bambara, and L. M. Demeter The P236L Delavirdine-Resistant Human Immunodeficiency Virus Type 1 Mutant Is Replication Defective and Demonstrates Alterations in both RNA 5'-End- and DNA 3'-End-Directed RNase H Activities J. Virol., July 1, 1999; 73(7): 5803 - 5813. [Abstract] [Full Text]

				C. Palaniappan, J. K. Kim, M. Wisniewski, P. J. Fay, and R. A. Bambara Control of Initiation of Viral Plus Strand DNA Synthesis by HIV Reverse Transcriptase J. Biol. Chem., February 13, 1998; 273(7): 3808 - 3816. [Abstract] [Full Text] [PDF]

				B. Chan and K. Musier-Forsyth The nucleocapsid protein specifically anneals tRNALys-3 onto a noncomplementary primer binding site within the HIV-1 RNA genome vitro PNAS, December 9, 1997; 94(25): 13530 - 13535. [Abstract] [Full Text] [PDF]