HSV-1 nucleocapsid egress mediated by UL31 in association with UL34 is impeded by cellular transmembrane protein 140

Virology. 2014 Sep:464-465:1-10. doi: 10.1016/j.virol.2014.06.034. Epub 2014 Jul 16.

Abstract

During HSV-1 infection, the viral UL31 protein forms a complex with the UL34 protein at the cellular nuclear membrane, where both proteins play important roles in the envelopment of viral nucleocapsids and their egress into the cytoplasm. To characterize the mechanism of HSV-1 nucleocapsid egress, we screened host proteins to identify proteins that interacted with UL31 via yeast two-hybrid analysis. Transmembrane protein 140 (TMEM140), was identified and confirmed to bind to and co-localize with UL31 during viral infection. Further studies indicated that TMEM140 inhibits HSV-1 proliferation through selectively blocking viral nucleocapsid egress during the viral assembly process. The blockage function of TMEM140 is mediated by impeding the formation of the UL31-UL34 complex due to competitive binding to UL31. Collectively, these data suggest the essentiality of the UL31-UL34 interaction in the viral nucleocapsid egress process and provide a new anti-HSV-1 strategy in viral assembly process of nucleocapsid egress.

Keywords: Herpes simplex virus 1 (HSV-1); Nucleocapsid egress; Transmembrane protein 140 (TMEM140); UL31; UL34.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Herpes Simplex / genetics
  • Herpes Simplex / metabolism*
  • Herpes Simplex / virology*
  • Herpesvirus 1, Human / chemistry
  • Herpesvirus 1, Human / genetics
  • Herpesvirus 1, Human / physiology*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleocapsid / genetics
  • Nucleocapsid / metabolism*
  • Protein Binding
  • Sequence Alignment
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Virus Assembly
  • Virus Release*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Nuclear Proteins
  • TMEM140 protein, human
  • UL31 protein, Human herpesvirus 1
  • UL34 protein, Human herpesvirus 1
  • Viral Proteins