News Release

How HIV DNA is blocked from entering the cell nucleus

Peer-Reviewed Publication

PLOS

How HIV DNA is Blocked from Entering the Cell Nucleus

image: Antibody staining and light microscopy demonstrate the accumulation and co-localization (yellow) of MX2 (red) and NUP214 (green) at the nuclear envelope. Image provided by Dr Gilberto Betancor; created by the superimposition of two images from Figure 6A view more 

Credit: Gilberto Betancor <em>et al</em>. (2018)

Multiple components of the nuclear pore complex and nuclear import machinery enable a protein called human myxovirus resistance 2 (MX2) to inhibit HIV-1 infection, according to a study published November 29 in the open-access journal PLOS Pathogens by Michael Malim of King's College London, and colleagues.

In eukaryotic cells, a membrane barrier called the nuclear envelope separates the nucleus from the cytoplasm. The movement of large molecules through the nuclear envelope and into the cell nucleus is regulated by large protein structures called nuclear pore complexes. To infect cells productively, HIV-1 must traverse the nuclear envelope to enable integration of the viral DNA into the genomic DNA of host cells. MX2, which is localized at the cytoplasmic face of the nuclear envelope, inhibits infection by blocking the nuclear import of HIV-1 DNA and preventing its accumulation within the nucleus. However, the precise mechanism of viral inhibition has not been clear.

In the new study, Malim and colleagues show that MX2 interacts with multiple protein components of the nuclear pore complex, as well as the nuclear transport receptor transportin-1 - a component of the nuclear import pathway. The findings suggest that TNPO1 and nucleoporins (particularly NUP214) help position MX2 at the nuclear envelope to promote MX2-mediated restriction of HIV-1. According to the authors, these new insights could lead to the development of more effective therapies for HIV-infected patients.

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Research Article

Peer-reviewed; Experimental study; Cells; People

Funding: The work was supported by the U.K. Medical Research Council (G1000196), the Wellcome Trust (106223/Z/14/Z), the National Institutes of Health (DA033773 and GM103368), a Long-Term Fellowship (ALTF 663-2016) of the European Molecular Biology Organization (EMBO) (to JMJG), the European Commission's Seventh Framework Programme (FP7/2007-2013) under grant agreement PIEF-GA-2009-237501 (to CG), the Guy's and St Thomas Charity, and the Department of Health via a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Dicks MDJ, Betancor G, Jimenez-Guardeño JM, Pessel-Vivares L, Apolonia L, Goujon C, et al. (2018) Multiple components of the nuclear pore complex interact with the amino-terminus of MX2 to facilitate HIV-1 restriction. PLoS Pathog 14(11): e1007408. https://doi.org/10.1371/journal.ppat.1007408

Author Affiliations:

Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, United Kingdom

In your coverage please use this URL to provide access to the freely available paper: http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat. 1007408


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