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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 29; pp. 10209 - 10214
• Main Authors: Utley, Thomas J, Ducharme, Nicole A, Varthakavi, Vasundhara, Shepherd, Bryan E, Santangelo, Philip J, Lindquist, Michael E, Goldenring, James R, Crowe, James E. Jr
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 22.07.2008; National Acad Sciences
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - physiology; Animals; ATPases Associated with Diverse Cellular Activities; Biological Sciences; Budding; Carrier Proteins - genetics; Carrier Proteins - physiology; Cell Line; Cell lines; Cells; Dogs; Endosomal Sorting Complexes Required for Transport; Endosomes - physiology; Endosomes - virology; Epithelial cells; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Host-Pathogen Interactions; Human respiratory syncytial virus; Humans; Inclusion bodies; Kidney cells; Membrane Proteins - genetics; Membrane Proteins - physiology; Membranes; Mutation; Protein folding; Proteins; rab GTP-Binding Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Recycling; Respiratory syncytial virus; Respiratory Syncytial Virus, Human - genetics; Respiratory Syncytial Virus, Human - growth & development; Respiratory Syncytial Virus, Human - pathogenicity; Respiratory Syncytial Virus, Human - physiology; Respiratory syncytial viruses; Ribonucleic acid; RNA; 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; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0712144105

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.