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Cited by 130HIV Research and TreatmentNuclear Structure and FunctionVirus-based gene therapy research

Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration

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Zhou, Lihong, Sokolskaja, Elena, Jolly, Clare, James, William, Cowley, Sally A., Fassati, Ariberto·2011·PLoS Pathogens
DOI 10.1371/journal.ppat.1002194PMC PMC3161976
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Abstract

The HIV/AIDS pandemic is a major global health threat and understanding the detailed molecular mechanisms of HIV replication is critical for the development of novel therapeutics. To replicate, HIV-1 must access the nucleus of infected cells and integrate into host chromosomes, however little is known about the events occurring post-nuclear entry but before integration. Here we show that the karyopherin Transportin 3 (Tnp3) promotes HIV-1 integration in different cell types. Furthermore Tnp3 binds the viral capsid proteins and tRNAs incorporated into viral particles. Interaction between Tnp3, capsid and tRNAs is stronger in the presence of RanGTP, consistent with the possibility that Tnp3 is an export factor for these substrates. In agreement with this interpretation, we found that Tnp3 exports from the nuclei viral tRNAs in a RanGTP-dependent way. Tnp3 also binds and exports from the nuclei some species of cellular tRNAs with a defective 3'CCA end. Depletion of Tnp3 results in a re-distribution of HIV-1 capsid proteins between nucleus and cytoplasm however HIV-1 bearing the N74D mutation in capsid, which is insensitive to Tnp3 depletion, does not show nucleocytoplasmic redistribution of capsid proteins. We propose that Tnp3 promotes HIV-1 infection by displacing any capsid and tRNA that remain bound to the pre-integration complex after nuclear entry to facilitate integration. The results also provide evidence for a novel tRNA nucleocytoplasmic trafficking pathway in human cells.

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Crossref · 10.1371/journal.ppat.1002194

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  • It has been proposed that the nuclear export of CA and tRNAs displaces them from the viral DNA, exposing the DNA to IN and other factors necessary for integration.

    “It has been proposed that the nuclear export of CA and tRNAs displaces them from the viral DNA, exposing the DNA to IN and other factors necessary for integration (120).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [120]

    The Results section (‘Tnp3 is an export factor for CA’; page not available) proposes that Tnp3 promotes a maturation step by possibly displacing CA and tRNAs still bound to the pre-integration complex. The cited passages do not say that this exposes viral DNA to integrase (IN) or other factors, so that specific mechanism is not supported by our copy. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Tnp3 interacts with HIV-1 CA and tRNAs lacking 3' CCA ends in the nucleus and facilitates their nuclear export.

    “Indeed, Tnp3 interacts with HIV-1 CA and tRNAs lacking 3Ј CCA ends in the nucleus and facilitates their nuclear export (120).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [120]

  • Transportin 3 (Tnp3) is required for efficient HIV-1 integration.

    “Transportin 3 (Tnp3), a host RNA-binding protein that participates in nucleocytoplasmic transport of nucleic acids and proteins, is required for efficient HIV-1 integration (120).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [120]

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Research works printed but not linked: 74

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Authors
Zhou, L., Sokolskaja, E., Jolly, C., James, W., Cowley, S. A., & Fassati, A.
Affiliations
  • University College London (GB)
  • University of Oxford (GB)
Corresponding author
Fassati, Ariberto
ORCID
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2011-08-25
Volume
7
Issue
8
Pages
e1002194
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1002194
PMC
PMC3161976
OpenAlex
W2022159627
Cited by
130
References
4
Citations by year
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FWCI
5.70
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • 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 › Genetics › Virus-based gene therapy research
Keywords
HIV-1 integration, karyopherins, preintegration complex, capsid protein, tRNA export, RanGTP, nucleocytoplasmic trafficking, nuclear maturation, HIV replication
MeSH terms
Cell Line, Cell Nucleus, Cloning, Molecular, DNA, Viral, Humans, Mutation, Protein Binding, RNA, Transfer, HIV-1, Virus Integration, Active Transport, Cell Nucleus, beta Karyopherins, Capsid Proteins

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