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  • Review Article
  • Published:

The road to chromatin — nuclear entry of retroviruses

Nature Reviews Microbiology volume 5, pages 187–196 (2007)Cite this article

Key Points

  • Integration of viral DNA into the host genome is an essential step in the replication cycle of human immunodeficiency virus 1 (HIV-1) and other retroviruses.

  • The viral DNA, which is synthesized by reverse transcription in the cytoplasm, is part of a very large nucleoprotein complex, the pre-integration complex (PIC), that must be transported to the nucleus before the DNA can be integrated. Motor proteins transport the PIC to the nucleus using the cytoskeleton as a highway.

  • HIV-1 can infect non-dividing cells, so HIV-1 PICs must cross the nuclear envelope. This is a formidable challenge, because PICs are very large compared with nuclear pores. Some other retroviruses only replicate efficiently in dividing cells, and their PICs might require the breakdown of the nuclear envelope during cell division to enter the nucleus.

  • Several viral proteins have been proposed to contain signals that target HIV-1 PICs to the nucleus. There might be more than one signal in each protein.

  • Nuclear entry of HIV-1 PICs is probably mediated by the importin pathway, which targets many cellular proteins to the nucleus.

  • Studying the nuclear entry of retroviral PICs should advance our basic knowledge of intracellular trafficking and will also facilitate the identification of novel antiviral targets and the design of improved retroviral vectors.

Abstract

Human immunodeficiency virus 1 (HIV-1) and other retroviruses synthesize a DNA copy of their genome after entry into the host cell. Integration of this DNA into the host cell's genome is an essential step in the viral replication cycle. The viral DNA is synthesized in the cytoplasm and is associated with viral and cellular proteins in a large nucleoprotein complex. Before integration into the host genome can occur, this complex must be transported to the nucleus and must cross the nuclear envelope. This Review summarizes our current knowledge of how this journey is accomplished.

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Figure 1: From cell entry to DNA integration.
Figure 2: Nuclear import of pre-integration complexes and the cell cycle.
Figure 3: HIV-1 proteins and PIC nuclear import.
Figure 4: LEDGF/p75 and nuclear entry of PICs.
Figure 5: Nuclear-envelope-associated proteins and retroviral DNA integration.

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Acknowledgements

This work was supported in part by the Intramural Research Programme of the National Institute of Diabetes and Digestive and Kidney Diseases (US National Intitutes of Health).

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Authors and Affiliations

  1. Laboratory for Host Factors, Center for Emerging Virus Research, Institute for Virus Research, Kyoto University, 53 Shogoin-Kawara-cho, Sakyo-ku, 606-8507, Kyoto, Japan

    Youichi Suzuki

  2. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Robert Craigie

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  1. Youichi Suzuki
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DATABASES

Entrez Genome

ASV

FIV

FrMLV

HFV

HIV-1

HIV-2

HSV

HTLV

MoMLV

SIV

spleen necrosis virus

SV40

vaccinia virus

Glossary

Karyophilic proteins

Proteins carrying signals that cause them to accumulate in the nucleus. This signal is typically a short peptide sequence called a nuclear localization signal.

Pleiotropic

A gene or mutation that is responsible for several distinct and seemingly unrelated phenotypic effects.

Interphase

The period between two mitotic divisions.

Transferable nuclear localization signal

A 7–9 amino-acid residue sequence in a protein, rich in basic residues, which acts as a signal for localization of the protein within the nucleus.

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Suzuki, Y., Craigie, R. The road to chromatin — nuclear entry of retroviruses. Nat Rev Microbiol 5, 187–196 (2007). https://doi.org/10.1038/nrmicro1579

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