Vaccinia virus p37 interacts with host proteins associated with LE-derived transport vesicle biogenesis

Virol J. 2009 Apr 28;6:44. doi: 10.1186/1743-422X-6-44.

Abstract

Background: Proteins associated with the late endosome (LE) appear to play a central role in the envelopment of a number of taxonomically diverse viruses. How viral proteins interact with LE-associated proteins to facilitate envelopment is not well understood. LE-derived transport vesicles form through the interaction of Rab9 GTPase with cargo proteins, and TIP47, a Rab9-specific effector protein. Vaccinia virus (VV) induces a wrapping complex derived from intracellular host membranes to envelope intracellular mature virus particles producing egress-competent forms of virus.

Results: We show that VV p37 protein associates with TIP47-, Rab9-, and CI-MPR-containing membranes. Mutation of a di-aromatic motif in p37 blocks association with TIP47 and inhibits plaque formation. ST-246, a specific inhibitor of p37 function, inhibits these interactions and also blocks wrapped virus particle formation. Vaccinia virus expressing p37 variants with reduced ST-246 susceptibility associates with Rab9 and co-localizes with CI-MPR in the presence and absence of compound.

Conclusion: These results suggest that p37 localizes to the LE and interacts with proteins associated with LE-derived transport vesicle biogenesis to facilitate assembly of extracellular forms of virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • Endosomes / metabolism*
  • Endosomes / virology
  • Humans
  • Intracellular Membranes / metabolism
  • Intracellular Membranes / virology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Perilipin-3
  • Pregnancy Proteins / metabolism*
  • Protein Binding
  • Receptor, IGF Type 2
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Transport Vesicles / metabolism*
  • Transport Vesicles / virology
  • Vaccinia / metabolism*
  • Vaccinia / virology
  • Vaccinia virus / genetics
  • Vaccinia virus / metabolism*
  • Vesicular Transport Proteins
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • rab GTP-Binding Proteins / metabolism*

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • PLIN3 protein, human
  • Perilipin-3
  • Pregnancy Proteins
  • Receptor, IGF Type 2
  • Receptors, Cytoplasmic and Nuclear
  • Vesicular Transport Proteins
  • Viral Envelope Proteins
  • cation-dependent mannose-6-phosphate receptor
  • p37 protein, Vaccinia virus
  • RAB9A protein, human
  • rab GTP-Binding Proteins