The Rab11 Pathway Is Required for Influenza A Virus Budding and Filament Formation

被引:153
作者
Bruce, Emily A. [1 ]
Digard, Paul [1 ]
Stuart, Amanda D. [1 ]
机构
[1] Univ Cambridge, Div Virol, Dept Pathol, Cambridge CB2 1QP, England
关键词
RESPIRATORY SYNCYTIAL VIRUS; PLASMA-MEMBRANE; MATRIX PROTEIN; RECYCLING ENDOSOME; EPITHELIAL-CELLS; RAB11-INTERACTING PROTEINS; ACTIN CYTOSKELETON; VIRAL MORPHOLOGY; CLEAVAGE FURROW; NUCLEAR EXPORT;
D O I
10.1128/JVI.00307-10
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Influenza A virus buds through the apical plasma membrane, forming enveloped virus particles that can take the shape of pleomorphic spheres or vastly elongated filaments. For either type of virion, the factors responsible for separation of viral and cell membranes are not known. We find that cellular Rab11 (a small GTP-binding protein involved in endocytic recycling) and Rab11-family interacting protein 3 ([FIP3] which plays a role in membrane trafficking and regulation of actin dynamics) are both required to support the formation of filamentous virions, while Rab11 is additionally involved in the final budding step of spherical particles. Cells transfected with Rab11 GTP-cycling mutants or depleted of Rab11 or FIP3 content by small interfering RNA treatment lost the ability to form virus filaments. Depletion of Rab11 resulted in up to a 100-fold decrease in titer of spherical virus released from cells. Scanning electron microscopy of Rab11-depleted cells showed high densities of virus particles apparently stalled in the process of budding. Transmission electron microscopy of thin sections confirmed that Rab11 depletion resulted in significant numbers of abnormally formed virus particles that had failed to pinch off from the plasma membrane. Based on these findings, we see a clear role for a Rab11-mediated pathway in influenza virus morphogenesis and budding.
引用
收藏
页码:5848 / 5859
页数:12
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