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The impact of host genetic variation on infection with HIV-1

Nature Immunology volume 16, pages 577–583 (2015)Cite this article

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Abstract

The outcome after infection with the human immunodeficiency virus type 1 (HIV-1) is a complex phenotype determined by interactions among the pathogen, the human host and the surrounding environment. An impact of host genetic variation on HIV-1 susceptibility was identified early in the pandemic, with a major role attributed to the genes encoding class I human leukocyte antigens (HLA) and the chemokine receptor CCR5. Studies using genome-wide data sets have underscored the strength of these associations relative to variants located throughout the rest of the genome. However, the extent to which additional polymorphisms influence HIV-1 disease progression, and how much of the variability in outcome can be attributed to host genetics, remain largely unclear. Here we discuss findings concerning the functional impact of associated variants, outline methods for quantifying the host genetic component and examine how available genome-wide data sets may be leveraged to discover gene variants that affect the outcome of HIV-1 infection.

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Figure 1: Opportunities and obstacles for human genetic studies of HIV-1 outcomes.
Figure 2: Approaches to supporting a direct functional impact of HLA-C expression on HIV-1 disease outcome.
Figure 3: HIV-1–dependency genes identified by genome-wide short interfering RNA (siRNA) screens are relatively conserved.

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Acknowledgements

We thank A. Bashirova and I. Bartha for helpful suggestions. This project was funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the National Institutes of Health, Frederick National Laboratory, Center for Cancer Research.

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  1. School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

    Paul J McLaren

  2. Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

    Mary Carrington

  3. The Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA

    Mary Carrington

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McLaren, P., Carrington, M. The impact of host genetic variation on infection with HIV-1. Nat Immunol 16, 577–583 (2015). https://doi.org/10.1038/ni.3147

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