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The inner-nuclear-envelope protein emerin regulates HIV-1 infectivity

Nature volume 441, pages 641645 (01 June 2006) | Download Citation

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Abstract

Primate lentiviruses such as human immunodeficiency type 1 (HIV-1) have the capacity to infect non-dividing cells such as tissue macrophages1. In the process, viral complementary DNA traverses the nuclear envelope to integrate within chromatin2. Given the intimate association between chromatin and the nuclear envelope3, we examined whether HIV-1 appropriates nuclear envelope components during infection. Here we show that emerin, an integral inner-nuclear-envelope protein, is necessary for HIV-1 infection. Infection of primary macrophages lacking emerin was abortive in that viral cDNA localized to the nucleus but integration into chromatin was inefficient, and conversion of viral cDNA to non-functional episomal cDNA increased. HIV-1 cDNA associated with emerin in vivo, and the interaction of viral cDNA with chromatin was dependent on emerin. Barrier-to-autointegration factor (BAF), the LEM (LAP, emerin, MAN) binding partner of emerin, was required for the association of viral cDNA with emerin and for the ability of emerin to support virus infection. Therefore emerin, which bridges the interface between the inner nuclear envelope and chromatin, may be necessary for chromatin engagement by viral cDNA before integration.

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Acknowledgements

We thank A. Dauphin and J. Zhou for research support, B. Mellor for preparation of the figures, K. Departie and L. Smith for manuscript preparation, and A. Engelman for providing HIV-1 integrase mutants. The University of Massachusetts Center for AIDS Research and the AIDS Research Reference Reagent Program, Division of AIDS, NIAID, National Institutes of Health (NIH), provided assay support and reagents. This study was supported by grants from the NIH to M.S.

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    • Jean-Marc Jacque

    †Present address: Centre for Research in Infectious Diseases, University College Dublin, Belfield, Dublin 4, Ireland

Affiliations

  1. Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Suite 319, Worcester, Massachusetts 01605, USA

    • Jean-Marc Jacque
    •  & Mario Stevenson

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Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Corresponding author

Correspondence to Mario Stevenson.

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    Supplementary Methods

    This file contains additional information on the methods used in this study, including Cells and siRNA transfections, PCR analysis and Western blotting. This file also contains additional references.

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https://doi.org/10.1038/nature04682

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