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Cell Host Microbe. 2016 Aug 10;20(2):178-88. doi: 10.1016/j.chom.2016.07.003.

An Intrinsically Disordered Region of the DNA Repair Protein Nbs1 Is a Species-Specific Barrier to Herpes Simplex Virus 1 in Primates.

Author information

1
Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
2
Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania and the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
3
BioFrontiers Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO 80303, USA.
4
Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania and the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Program, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
5
Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT 06030, USA.
6
Department of Biology, Stanford University, Stanford, CA 94305, USA.
7
Division of Cancer Pathobiology, Department of Pathology and Laboratory Medicine, The Perelman School of Medicine at the University of Pennsylvania and the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address: weitzmanm@email.chop.edu.
8
Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA; BioFrontiers Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO 80303, USA. Electronic address: ssawyer@colorado.edu.

Abstract

Humans occasionally transmit herpes simplex virus 1 (HSV-1) to captive primates, who reciprocally harbor alphaherpesviruses poised for zoonotic transmission to humans. To understand the basis for the species-specific restriction of HSV-1 in primates, we simulated what might happen during the cross-species transmission of HSV-1 and found that the DNA repair protein Nbs1 from only some primate species is able to promote HSV-1 infection. The Nbs1 homologs that promote HSV-1 infection also interact with the HSV-1 ICP0 protein. ICP0 interaction mapped to a region of structural disorder in the Nbs1 protein. Chimeras reversing patterns of disorder in Nbs1 reversed titers of HSV-1 produced in the cell. By extending this analysis to 1,237 virus-interacting mammalian proteins, we show that proteins that interact with viruses are highly enriched in disorder, suggesting that viruses commonly interact with host proteins through intrinsically disordered domains.

PMID:
27512903
PMCID:
PMC4982468
DOI:
10.1016/j.chom.2016.07.003
[Indexed for MEDLINE]
Free PMC Article

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