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Intrinsic host restrictions to HIV-1 and mechanisms of viral escape

Nature Immunology volume 16, pages 546–553 (2015)Cite this article

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Abstract

To replicate in their hosts, viruses have to navigate the complexities of the mammalian cell, co-opting mechanisms of cellular physiology while defeating restriction factors that are dedicated to halting their progression. Primate lentiviruses devote a relatively large portion of their coding capacity to counteracting restriction factors by encoding accessory proteins dedicated to neutralizing the antiviral function of these intracellular inhibitors. Research into the roles of the accessory proteins has revealed the existence of previously undetected intrinsic defenses, provided insight into the evolution of primate lentiviruses as they adapt to new species and uncovered new targets for the development of therapeutics. This Review discusses the biology of the restriction factors APOBEC3, SAMHD1 and tetherin and the viral accessory proteins that counteract them.

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Figure 1: The host restriction factors SAMHD1, APOBEC3 and tetherin, and the lentiviral accessory proteins that counteract them in the context of virus replication.
Figure 2: Overview of the mode of APOBEC3 (A3) restriction and the implications of suboptimal Vif activity on HIV transmission and diversification.
Figure 3: Proposed models for SAMHD1-mediated restriction.
Figure 4: Tetherin blocks virus release, activates an innate immune response and is counteracted by Vpu or Nef.

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Acknowledgements

We thank M. Ooms and L.C.F. Mulder for critical reading of the manuscript. The work was supported by US National Institutes of Health/National Institute of Allergy and Infectious Disease grants to V.S. (AI064001, AI090935) and N.R.L. (AI067059, AI058864), the Vilcek Fellowship Endowment Fund to N.B. and the American Foundation for AIDS Research.

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  1. Department of Microbiology, The Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA

    Viviana Simon

  2. Department of Microbiology, NYU School of Medicine, New York, New York, USA

    Nicolin Bloch & Nathaniel R Landau

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  1. Viviana Simon
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Correspondence to Nathaniel R Landau.

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Simon, V., Bloch, N. & Landau, N. Intrinsic host restrictions to HIV-1 and mechanisms of viral escape. Nat Immunol 16, 546–553 (2015). https://doi.org/10.1038/ni.3156

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