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

Utley TJ, Ducharme NA, Varthakavi V, Shepherd BE, Santangelo PJ, Lindquist ME, Goldenring JR, Crowe JE
Proc Natl Acad Sci U S A. 2008 105 (29): 10209-14

PMID: 18621683 · PMCID: PMC2481327 · 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.

MeSH Terms (22)

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

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