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J Virol. 2011 Apr 27. [Epub ahead of print]
RAB11A is Essential for Influenza Genome Transport to the Plasma Membrane.
Eisfeld AJ, Kawakami E, Watanabe T, Neumann G, Kawaoka Y.
Source
University of Wisconsin-Madison, School of Veterinary Medicine, Department of Pathobiological Sciences, Influenza Research Institute, 575 Science Drive, Madison, WI, 53711, USA.
Abstract
Influenza A virus assembly is a complex process that requires the intersection of pathways involved in transporting viral glycoproteins, the matrix protein and viral genomes, incorporated in the viral ribonucleoprotein (vRNP) complex, to plasma membrane sites of virion formation. Among these virion components, the mechanism of vRNP delivery is the most incompletely understood. Here, we reveal a functional relationship between the cellular Rab11 GTPase isoform, RAB11A, and vRNPs and show that RAB11A is indispensible for proper vRNP transport to the plasma membrane. Using an immunofluorescence-based assay with a monoclonal antibody that recognizes nucleoprotein in the form of vRNP, we demonstrate association between RAB11A and vRNPs at all stages of vRNP cytoplasmic transport. Abrogation of RAB11A expression through siRNA treatment or disruption of RAB11A function by overexpression of dominant negative or constitutively active proteins caused aberrant vRNP intracellular accumulation, retention in the perinuclear region, and lack of accumulation at the plasma membrane. Complex formation between RAB11A and vRNP was further established biochemically. Our results uncover a critical host factor with an essential contribution to influenza genome delivery, and reveal a potential role for RAB11A in the transport of ribonucleoprotein cargo.
PMID:
21525351
[PubMed - as supplied by publisher]
RAB11A is Essential for Influenza Genome Transport to the Plasma Membrane.
Eisfeld AJ, Kawakami E, Watanabe T, Neumann G, Kawaoka Y.
Source
University of Wisconsin-Madison, School of Veterinary Medicine, Department of Pathobiological Sciences, Influenza Research Institute, 575 Science Drive, Madison, WI, 53711, USA.
Abstract
Influenza A virus assembly is a complex process that requires the intersection of pathways involved in transporting viral glycoproteins, the matrix protein and viral genomes, incorporated in the viral ribonucleoprotein (vRNP) complex, to plasma membrane sites of virion formation. Among these virion components, the mechanism of vRNP delivery is the most incompletely understood. Here, we reveal a functional relationship between the cellular Rab11 GTPase isoform, RAB11A, and vRNPs and show that RAB11A is indispensible for proper vRNP transport to the plasma membrane. Using an immunofluorescence-based assay with a monoclonal antibody that recognizes nucleoprotein in the form of vRNP, we demonstrate association between RAB11A and vRNPs at all stages of vRNP cytoplasmic transport. Abrogation of RAB11A expression through siRNA treatment or disruption of RAB11A function by overexpression of dominant negative or constitutively active proteins caused aberrant vRNP intracellular accumulation, retention in the perinuclear region, and lack of accumulation at the plasma membrane. Complex formation between RAB11A and vRNP was further established biochemically. Our results uncover a critical host factor with an essential contribution to influenza genome delivery, and reveal a potential role for RAB11A in the transport of ribonucleoprotein cargo.
PMID:
21525351
[PubMed - as supplied by publisher]
