Specific initiation and switch to elongation of human immunodeficiency virus type 1 reverse transcription require the post-transcriptional modifications of primer tRNA3Lys.

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Specific initiation and switch to elongation of human immunodeficiency virus type 1 reverse transcription require the post-transcriptional modifications of primer tRNA3Lys.

EMBO J. 1996 Feb 15;15(4):917-24. Unique Identifier : AIDSLINE MED/96181369
Isel C; Lanchy JM; Le Grice SF; Ehresmann C; Ehresmann B; Marquet R; Unite Propre de Recherche 9002 du Centre National de la; Recherche Scientifique, Strasbourg, France.

Abstract: Initiation of RNA-dependent DNA synthesis by retroviral reverse transcriptases is generally considered as unspecific. In the case of human immunodeficiency virus type 1 (HIV-1), the natural primer is tRNA3Lys. We recently found evidence of complex interactions between tRNA3Lys and HIV-1 RNA that may be involved in the priming process. In this study, we compare the ability of natural and unmodified synthetic tRNA3Lys and 18mer oligoribo- and oligodeoxyribonucleotides complementary to the viral primer binding site to initiate replication of HIV-1 RNA using either homologous or heterologous reverse transcriptases. We show that HIV-1 RNA, HIV-1 reverse transcriptase and primer tRNA3Lys form a specific initiation complex that differs from the unspecific elongation complex formed when an oligodeoxyribonucleotide is used as primer. Modified nucleosides of tRNA3Lys are required for efficient initiation and transition to elongation. Transition from initiation to elongation, but not initiation of reverse transcription itself, is facilitated by extended primer-template interactions. Elongation, but not initiation of reverse transcription, is inhibited by Mn2+, which further differentiates these two different functional states of reverse transcriptase. These results define initiation of reverse transcription as a target to block viral replication.

Keywords: Cell-Free System Gene Expression Regulation, Viral HIV-1/*GENETICS RNA-Directed DNA Polymerase/*METABOLISM RNA, Transfer, Lys/*METABOLISM RNA, Viral/METABOLISM Support, Non-U.S. Gov't Templates *Virus Replication JOURNAL ARTICLE
960930
M9690917

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