title: An Intrinsically Disordered Region of the DNA Repair Protein Nbs1 Is a Species-Specific Barrier to Herpes Simplex Virus 1 in Primates.
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.
authors: Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
authors: Dianne I
authors: DI
authors: Lou
authors: 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.
authors: Eui Tae
authors: ET
authors: Kim
authors: BioFrontiers Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO 80303, USA.
authors: Nicholas R
authors: NR
authors: Meyerson
authors: 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.
authors: Neha J
authors: NJ
authors: Pancholi
authors: Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Kareem N
authors: KN
authors: Mohni
authors: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors: David
authors: D
authors: Enard
authors: Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors: Dmitri A
authors: DA
authors: Petrov
authors: Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Sandra K
authors: SK
authors: Weller
authors: 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.
authors: Matthew D
authors: MD
authors: Weitzman
authors: 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.
authors: Sara L
authors: SL
authors: Sawyer
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011323:Primates; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D017386:Sequence Homology, Amino Acid; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D045643:DNA Repair Enzymes