A Herpesvirus Protein Selectively Inhibits Cellular mRNA Nuclear Export

Cell Host Microbe. 2016 Nov 9;20(5):642-653. doi: 10.1016/j.chom.2016.10.004.


Nuclear mRNA export is highly regulated to ensure accurate cellular gene expression. Viral inhibition of cellular mRNA export can enhance viral access to the cellular translation machinery and prevent anti-viral protein production but is generally thought to be nonselective. We report that ORF10 of Kaposi's sarcoma-associated herpesvirus (KSHV), a nuclear DNA virus, inhibits mRNA export in a transcript-selective manner to control cellular gene expression. Nuclear export inhibition by ORF10 requires an interaction with an RNA export factor, Rae1. Genome-wide analysis reveals a subset of cellular mRNAs whose nuclear export is blocked by ORF10 with the 3' UTRs of ORF10-targeted transcripts conferring sensitivity to export inhibition. The ORF10-Rae1 interaction is important for the virus to express viral genes and produce infectious virions. These results suggest that a nuclear DNA virus can selectively interfere with RNA export to restrict host gene expression for optimal replication.

Keywords: 3′ UTR; KSHV; Nup98; ORF10; Rae1; herpesvirus; late gene; mRNA nuclear export.

MeSH terms

  • Active Transport, Cell Nucleus*
  • Animals
  • Cell Line
  • Gene Expression Regulation
  • Herpesvirus 8, Human / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Models, Biological
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Protein Binding
  • RNA, Messenger / metabolism*
  • Viral Proteins / metabolism*
  • Virus Replication*


  • Nuclear Matrix-Associated Proteins
  • Nucleocytoplasmic Transport Proteins
  • RAE1 protein, human
  • RNA, Messenger
  • Viral Proteins