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tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes

Zaitseva, L; Myers, R; Fassati, A; (2006) tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes. PLOS BIOL , 4 (10) , Article e332. 10.1371/journal.pbio.0040332. Green open access

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Abstract

Infection of non-dividing cells is a biological property of HIV-1 crucial for virus transmission and AIDS pathogenesis. This property depends on nuclear import of the intracellular reverse transcription and pre-integration complexes (RTCs/PICs). To identify cellular factors involved in nuclear import of HIV-1 RTCs, cytosolic extracts were fractionated by chromatography and import activity examined by the nuclear import assay. A near-homogeneous fraction was obtained, which was active in inducing nuclear import of purified and labeled RTCs. The active fraction contained tRNAs, mostly with defective 3' CCA ends. Such tRNAs promoted HIV-1 RTC nuclear import when synthesized in vitro. Active tRNAs were incorporated into and recovered from virus particles. Mutational analyses indicated that the anticodon loop mediated binding to the viral complex whereas the T-arm may interact with cellular factors involved in nuclear import. These tRNA species efficiently accumulated into the nucleus on their own in a energy- and temperature-dependent way. An HIV-1 mutant containing MLV gag did not incorporate tRNA species capable of inducing HIV-1 RTC nuclear import and failed to infect cell cycle-arrested cells. Here we provide evidence that at least some tRNA species can be imported into the nucleus of human cells and promote HIV-1 nuclear import.

Type: Article
Title: tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pbio.0040332
Publisher version: http://dx.doi.org/10.1371/journal.pbio.0040332
Additional information: © 2006 Zaitseva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: HUMAN-IMMUNODEFICIENCY-VIRUS, DIRECTED DNA-SYNTHESIS, CD4(+) T-CELLS, NONDIVIDING CELLS, MAMMALIAN-CELLS, PROTEIN IMPORT, INFECTION, TRANSPORT, TYPE-1, EXPORT
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/6990
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