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

Dianne I. Lou, Eui Tae Kim, Nicholas R. Meyerson, Neha J. Pancholi, Kareem N. Mohni, David Enard, Dmitri A. Petrov, Sandra K. Weller, Matthew D. Weitzman, Sara L. Sawyer

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)178-188
Number of pages11
JournalCell Host and Microbe
Volume20
Issue number2
DOIs
StatePublished - Aug 10 2016
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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