Inhibition of HIV-1 replication using a mutated tRNA(Lys-3) primer

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, Joseph D Rosenblatt

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 vital 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.

Original languageEnglish
Pages (from-to)14523-14531
Number of pages9
JournalJournal of Biological Chemistry
Volume272
Issue number23
DOIs
StatePublished - Jun 6 1997
Externally publishedYes

Fingerprint

RNA, Transfer, Lys
Transcription
Virus Replication
Viruses
HIV-1
Binding Sites
Transfer RNA
Reverse Transcription
T-cells
Antiviral Agents
Genes
Derivatives
Giant Cells
Genome
T-Lymphocytes
Mutation
Human immunodeficiency virus 1 reverse transcriptase

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lu, Y., Planelles, V., Li, X., Palaniappan, C., Day, B., Challita-Eid, P., ... Rosenblatt, J. D. (1997). Inhibition of HIV-1 replication using a mutated tRNA(Lys-3) primer. Journal of Biological Chemistry, 272(23), 14523-14531. https://doi.org/10.1074/jbc.272.23.14523

Inhibition of HIV-1 replication using a mutated tRNA(Lys-3) primer. / Lu, Yuanan; Planelles, Vicente; Li, Xinqiang; Palaniappan, Chockalingam; Day, Brian; Challita-Eid, Pia; Amado, Rafael; Stephens, Dennis; Kohn, Donald B.; Bakker, Andreas; Fay, Philip; Bambara, Robert A.; Rosenblatt, Joseph D.

In: Journal of Biological Chemistry, Vol. 272, No. 23, 06.06.1997, p. 14523-14531.

Research output: Contribution to journalArticle

Lu, Y, Planelles, V, Li, X, Palaniappan, C, Day, B, Challita-Eid, P, Amado, R, Stephens, D, Kohn, DB, Bakker, A, Fay, P, Bambara, RA & Rosenblatt, JD 1997, 'Inhibition of HIV-1 replication using a mutated tRNA(Lys-3) primer', Journal of Biological Chemistry, vol. 272, no. 23, pp. 14523-14531. https://doi.org/10.1074/jbc.272.23.14523
Lu Y, Planelles V, Li X, Palaniappan C, Day B, Challita-Eid P et al. Inhibition of HIV-1 replication using a mutated tRNA(Lys-3) primer. Journal of Biological Chemistry. 1997 Jun 6;272(23):14523-14531. https://doi.org/10.1074/jbc.272.23.14523
Lu, Yuanan ; Planelles, Vicente ; Li, Xinqiang ; Palaniappan, Chockalingam ; Day, Brian ; Challita-Eid, Pia ; Amado, Rafael ; Stephens, Dennis ; Kohn, Donald B. ; Bakker, Andreas ; Fay, Philip ; Bambara, Robert A. ; Rosenblatt, Joseph D. / Inhibition of HIV-1 replication using a mutated tRNA(Lys-3) primer. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 23. pp. 14523-14531.
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