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

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16 Scopus citations

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

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lu, Y., Planelles, V., Li, X., Palaniappan, C., Day, B., Challita-Eid, P., Amado, R., Stephens, D., Kohn, D. B., Bakker, A., Fay, P., Bambara, R. A., & 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