Cited by 104HIV Research and TreatmentNuclear Structure and FunctionRNA and protein synthesis mechanisms

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

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Zaitseva, Lyubov, Myers, Richard, Fassati, Ariberto·2006·PLoS Biology

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.

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  1. Freed EO Martin MA 2001 HIVs and their replication Knipe DM Howley PM Fields virology.Lippincott Williams & Wilkins 1971 2041
  2. Cohen OJ Fauci AS 2001 Pathogenesis and medical aspects of HIV-1 infection Knipe DM Howley PM Fields virology. Lippincott Williams & Wilkins 2043 2094

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Authors
Zaitseva, L., Myers, R., & Fassati, A.
Affiliations
University College London (GB)
Corresponding author
Fassati, Ariberto
Venue
PLoS Biology
Published
2006-10-03
Volume
4
Issue
10
Pages
e332
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
OpenAlex
W2048324943
Cited by
104
References
59
Citations by year
2026: 1 · 2025: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 4 · 2019: 6 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 9 · 2014: 2 · 2013: 10 · 2012: 8
FWCI
3.47
Type
journal article
Language
en
Open access
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
Wellcome Trust
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
HIV-1, tRNA, nuclear import, preintegration complex, anticodon loop, cell cycle arrest, non-dividing cells, cellular factors
MeSH terms
Anticodon, Cell Nucleus, Cells, Cultured, DNA, Viral, Humans, RNA, Transfer, HIV-1, Gene Products, gag, Jurkat Cells, Active Transport, Cell Nucleus, RNA, Small Interfering, Reverse Transcription, HIV Reverse Transcriptase

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