title: Respiratory syncytial virus uses a Vps4-independent budding mechanism controlled by Rab11-FIP2.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Utley
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Ducharme
authors.forename: Vasundhara
authors.initials: V
authors.lastname: Varthakavi
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Shepherd
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Santangelo
authors.forename: Michael E
authors.initials: ME
authors.lastname: Lindquist
authors.forename: James R
authors.initials: JR
authors.lastname: Goldenring
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004285:Dogs; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000502:physiology / Q000821:virology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity / Q000502:physiology*; D014162:Transfection; D025262:Vacuolar Proton-Translocating ATPases; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000502:physiology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology; D019065:Virus Assembly; D017201:Virus Shedding; D020691:rab GTP-Binding Proteins
chemical_list: D002352:Carrier Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; D014763:Viral Matrix Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000251:Adenosine Triphosphatases; D025262:Vacuolar Proton-Translocating ATPases; D000074183:ATPases Associated with Diverse Cellular Activities; C490305:VPS4A protein, human; C463963:RAB11FIP2 protein, human; D020691:rab GTP-Binding Proteins