Respiratory syncytial virus uses a Vps4-independent budding mechanism controlled by Rab11-FIP2

Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):10209-14. doi: 10.1073/pnas.0712144105. Epub 2008 Jul 9.


Respiratory syncytial virus (RSV) infects polarized epithelia, which have tightly regulated trafficking because of the separation and maintenance of the apical and basolateral membranes. Previously we established a link between the apical recycling endosome (ARE) and the assembly of RSV. The current studies tested the role of a major ARE-associated protein, Rab11 family interacting protein 2 (FIP2) in the virus life cycle. A dominant-negative form of FIP2 lacking its N-terminal C2 domain reduced the supernatant-associated RSV titer 1,000-fold and also caused the cell-associated virus titer to increase. These data suggested that the FIP2 C2 mutant caused a failure at the final budding step in the virus life cycle. Additionally, truncation of the Rab-binding domain from FIP2 caused its accumulation into mature filamentous virions. RSV budding was independent of the ESCRT machinery, the only well-defined budding mechanism for enveloped RNA viruses. Therefore, RSV uses a virus budding mechanism that is controlled by FIP2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / physiology
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Line
  • Dogs
  • Endosomal Sorting Complexes Required for Transport
  • Endosomes / physiology
  • Endosomes / virology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mutation
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Respiratory Syncytial Virus, Human / genetics
  • Respiratory Syncytial Virus, Human / growth & development*
  • Respiratory Syncytial Virus, Human / pathogenicity
  • Respiratory Syncytial Virus, Human / physiology*
  • Transfection
  • Vacuolar Proton-Translocating ATPases
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / physiology
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / physiology
  • Virus Assembly
  • Virus Shedding
  • rab GTP-Binding Proteins


  • Carrier Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • Vesicular Transport Proteins
  • Viral Matrix Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Adenosine Triphosphatases
  • Vacuolar Proton-Translocating ATPases
  • ATPases Associated with Diverse Cellular Activities
  • VPS4A protein, human
  • RAB11FIP2 protein, human
  • rab GTP-Binding Proteins