Apical Transport of Influenza A Virus Ribonucleoprotein Requires Rab11-positive Recycling Endosome

Influenza A virus RNA genome exists as eight-segmented ribonucleoprotein complexes containing viral RNA polymerase and nucleoprotein (vRNPs). Packaging of vRNPs and virus budding take place at the apical plasma membrane (APM). However, little is known about the molecular mechanisms of apical transport of newly synthesized vRNP. Transfection of fluorescent-labeled antibody and subsequent live cell imaging revealed that punctate vRNP signals moved along microtubules rapidly but intermittently in both directions, suggestive of vesicle trafficking. Using a series of Rab family protein, we demonstrated that progeny vRNP localized to recycling endosome (RE) in an active/GTP-bound Rab11-dependent manner. The vRNP interacted with Rab11 through viral RNA polymerase. The localization of vRNP to RE and subsequent accumulation to the APM were impaired by overexpression of Rab binding domains (RBD) of Rab11 family interacting proteins (Rab11-FIPs). Similarly, no APM accumulation was observed by overexpression of class II Rab11-FIP mutants lacking RBD. These results suggest that the progeny vRNP makes use of Rab11-dependent RE machinery for APM trafficking.

[1]  Andrew J. Lindsay,et al.  Rab Coupling Protein (RCP), a Novel Rab4 and Rab11 Effector Protein* , 2002, The Journal of Biological Chemistry.

[2]  Zhi-ping Zhang,et al.  Visualizing the dynamic behavior of poliovirus plus-strand RNA in living host cells , 2005, Nucleic acids research.

[3]  M. Amorim,et al.  A Rab11- and Microtubule-Dependent Mechanism for Cytoplasmic Transport of Influenza A Virus Viral RNA , 2011, Journal of Virology.

[4]  Giovanni Cardone,et al.  Influenza virus pleiomorphy characterized by cryoelectron tomography , 2006, Proceedings of the National Academy of Sciences.

[5]  A Helenius,et al.  Infectious entry pathway of influenza virus in a canine kidney cell line , 1981, The Journal of cell biology.

[6]  N. Dimmock,et al.  Defective segment 1 RNAs that interfere with production of infectious influenza A virus require at least 150 nucleotides of 5' sequence: evidence from a plasmid-driven system. , 2002, The Journal of general virology.

[7]  U. Greber,et al.  A Superhighway to Virus Infection , 2006, Cell.

[8]  R. Webster,et al.  Localization of RNA polymerases on influenza viral ribonucleoproteins by immunogold labeling. , 1988, Virology.

[9]  B. Moss,et al.  Vaccinia Virus Intracellular Movement Is Associated with Microtubules and Independent of Actin Tails , 2001, Journal of Virology.

[10]  A. Pekosz,et al.  Roles for the recycling endosome, Rab8, and Rab11 in hantavirus release from epithelial cells , 2008, Virology.

[11]  M. Marsh,et al.  SFV infection in CHO cells: cell-type specific restrictions to productive virus entry at the cell surface. , 1997, Journal of cell science.

[12]  Nicole A. Ducharme,et al.  Respiratory syncytial virus uses a Vps4-independent budding mechanism controlled by Rab11-FIP2 , 2008, Proceedings of the National Academy of Sciences.

[13]  J. McCauley,et al.  Defective RNAs inhibit the assembly of influenza virus genome segments in a segment-specific manner. , 1996, Virology.

[14]  B. Sodeik,et al.  Mechanisms of viral transport in the cytoplasm. , 2000, Trends in microbiology.

[15]  Subrata Barman,et al.  Assembly and budding of influenza virus , 2004, Virus Research.

[16]  C. Horgan,et al.  The dynamic Rab11-FIPs. , 2009, Biochemical Society transactions.

[17]  Eunjoon Kim,et al.  Characterization of the Movement of the Kinesin Motor KIF1A in Living Cultured Neurons* 210 , 2003, The Journal of Biological Chemistry.

[18]  N. Tommerup,et al.  Human rab11a: transcription, chromosome mapping and effect on the expression levels of host GTP‐binding proteins , 1998, FEBS letters.

[19]  H. Inoue,et al.  Arf GTPase-activating protein ASAP1 interacts with Rab11 effector FIP3 and regulates pericentrosomal localization of transferrin receptor-positive recycling endosome. , 2008, Molecular biology of the cell.

[20]  S. Fuller,et al.  Vesicular stomatitis virus infects and matures only through the basolateral surface of the polarized epithelial cell line, MDCK , 1984, Cell.

[21]  N. Daigle,et al.  Nuclear Import and Assembly of Influenza A Virus RNA Polymerase Studied in Live Cells by Fluorescence Cross-Correlation Spectroscopy , 2009, Journal of Virology.

[22]  J. Salamero,et al.  Rab11 Regulates the Compartmentalization of Early Endosomes Required for Efficient Transport from Early Endosomes to the Trans-Golgi Network , 2000, The Journal of cell biology.

[23]  Kenneth W Dunn,et al.  Rab10 regulates membrane transport through early endosomes of polarized Madin-Darby canine kidney cells. , 2006, Molecular biology of the cell.

[24]  P. Peters,et al.  Rab17 Localizes to Recycling Endosomes and Regulates Receptor-mediated Transcytosis in Epithelial Cells* , 1998, The Journal of Biological Chemistry.

[25]  Soichi Wakatsuki,et al.  Structural basis for Rab11-dependent membrane recruitment of a family of Rab11-interacting protein 3 (FIP3)/Arfophilin-1 , 2006, Proceedings of the National Academy of Sciences.

[26]  P. Digard,et al.  The Rab11 Pathway Is Required for Influenza A Virus Budding and Filament Formation , 2010, Journal of Virology.

[27]  Benjamin Thomas,et al.  Role of Ran Binding Protein 5 in Nuclear Import and Assembly of the Influenza Virus RNA Polymerase Complex , 2006, Journal of Virology.

[28]  H. Zentgraf,et al.  Characterization of Prototype Foamy Virus Gag Late Assembly Domain Motifs and Their Role in Particle Egress and Infectivity , 2005, Journal of Virology.

[29]  W. Doerfler,et al.  Structure and composition of the adenovirus type 2 core , 1975, Journal of virology.

[30]  A. Kawaguchi,et al.  Involvement of Hsp90 in Assembly and Nuclear Import of Influenza Virus RNA Polymerase Subunits , 2006, Journal of Virology.

[31]  G. Bao,et al.  Dynamics of filamentous viral RNPs prior to egress , 2007, Nucleic acids research.

[32]  R. Krug,et al.  Influenza virus gene expression: control mechanisms at early and late times of infection and nuclear-cytoplasmic transport of virus-specific RNAs , 1987, Journal of virology.

[33]  Julia R Gog,et al.  Genome packaging in influenza A virus. , 2010, The Journal of general virology.

[34]  Andrew J. Lindsay,et al.  Rab11-FIP4 interacts with Rab11 in a GTP-dependent manner and its overexpression condenses the Rab11 positive compartment in HeLa cells. , 2002, Biochemical and biophysical research communications.

[35]  D. Sabatini,et al.  Asymmetric budding of viruses in epithelial monlayers: a model system for study of epithelial polarity. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[36]  M. Zerial,et al.  Rab17 Regulates Membrane Trafficking through Apical Recycling Endosomes in Polarized Epithelial Cells , 1998, The Journal of cell biology.

[37]  R. Scheller,et al.  A Rab11/Rip11 protein complex regulates apical membrane trafficking via recycling endosomes. , 2000, Molecular cell.

[38]  Yuko Morikawa,et al.  Visualization of microtubule-mediated transport of influenza viral progeny ribonucleoprotein. , 2007, Microbes and infection.

[39]  M. Zerial,et al.  Rab11 regulates recycling through the pericentriolar recycling endosome , 1996, The Journal of cell biology.

[40]  P. Palese,et al.  The 3' and 5'-terminal sequences of influenza A, B and C virus RNA segments are highly conserved and show partial inverted complementarity. , 1980, Gene.

[41]  Z. Ye,et al.  Association of Influenza Virus Matrix Protein with Ribonucleoproteins , 1999, Journal of Virology.

[42]  Michael D. Abràmoff,et al.  Image processing with ImageJ , 2004 .

[43]  R. Prekeris,et al.  Polarized endocytic transport: the roles of Rab11 and Rab11-FIPs in regulating cell polarity. , 2009, Histology and histopathology.

[44]  G. Nemerow,et al.  Adenovirus Internalization and Infection Require Dynamin , 1998, Journal of Virology.

[45]  R. Lamb,et al.  Evidence for a New Viral Late-Domain Core Sequence, FPIV, Necessary for Budding of a Paramyxovirus , 2005, Journal of Virology.

[46]  D. Sabatini,et al.  Hydrolysis of GTP on rab11 is required for the direct delivery of transferrin from the pericentriolar recycling compartment to the cell surface but not from sorting endosomes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[47]  J. Goldenring,et al.  Regulation of Vesicle Trafficking in Madin-Darby Canine Kidney Cells by Rab11a and Rab25* , 2000, The Journal of Biological Chemistry.

[48]  M. Law,et al.  Vaccinia virus utilizes microtubules for movement to the cell surface , 2001, The Journal of cell biology.

[49]  F. Baudin,et al.  Influenza virus M1 protein binds to RNA through its nuclear localization signal. , 1997, The Journal of general virology.

[50]  M. Center,et al.  DNA-binding properties of the major core protein of adenovirus 2. , 1979, Nucleic acids research.

[51]  Wesley I. Sundquist,et al.  Tsg101 and the Vacuolar Protein Sorting Pathway Are Essential for HIV-1 Budding , 2001, Cell.

[52]  G. Nemerow,et al.  Adenovirus Endocytosis Requires Actin Cytoskeleton Reorganization Mediated by Rho Family GTPases , 1998, Journal of Virology.

[53]  P. Digard,et al.  The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. , 2002, The Journal of general virology.

[54]  T. Noda,et al.  Architecture of ribonucleoprotein complexes in influenza A virus particles , 2006, Nature.

[55]  Chadwick M. Hales,et al.  Identification and Characterization of a Family of Rab11-interacting Proteins* , 2001, The Journal of Biological Chemistry.

[56]  B. Klupp,et al.  Herpesvirus assembly: an update. , 2009, Virus research.

[57]  J. Parvin,et al.  Genomic RNAs of influenza viruses are held in a circular conformation in virions and in infected cells by a terminal panhandle. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[58]  J. McCauley,et al.  Edinburgh Research Explorer Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway , 2022 .

[59]  Hideo Goto,et al.  Selective incorporation of influenza virus RNA segments into virions , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[60]  S. Cusack,et al.  Three-dimensional model for the isolated recombinant influenza virus polymerase heterotrimer , 2007, Nucleic acids research.

[61]  T. Zimmermann,et al.  Kinesin-dependent movement on microtubules precedes actin-based motility of vaccinia virus , 2001, Nature Cell Biology.

[62]  M. Tashiro,et al.  Segment-specific noncoding sequences of the influenza virus genome RNA are involved in the specific competition between defective interfering RNA and its progenitor RNA segment at the virion assembly step , 1997, Journal of virology.

[63]  A. Wandinger-Ness,et al.  Rab GTPases at a glance , 2007, Journal of Cell Science.

[64]  Y. Altschuler,et al.  Association of Rab25 and Rab11a with the apical recycling system of polarized Madin-Darby canine kidney cells. , 1999, Molecular biology of the cell.

[65]  Alexander V. Zhdanov,et al.  Rab11‐FIP3 Is Critical for the Structural Integrity of the Endosomal Recycling Compartment , 2007, Traffic.

[66]  F. Baudin,et al.  Roles of the influenza virus polymerase and nucleoprotein in forming a functional RNP structure , 1997, The EMBO journal.

[67]  J. Goldenring,et al.  The Rab11-FIP1/RCP gene codes for multiple protein transcripts related to the plasma membrane recycling system. , 2006, Biochimica et biophysica acta.

[68]  R. Lamb,et al.  Mechanisms for enveloped virus budding: can some viruses do without an ESCRT? , 2008, Virology.

[69]  H. Stenmark Rab GTPases as coordinators of vesicle traffic , 2009, Nature Reviews Molecular Cell Biology.

[70]  G. Apodaca,et al.  Differential involvement of endocytic compartments in the biosynthetic traffic of apical proteins , 2007, The EMBO journal.

[71]  R. Lamb,et al.  Influenza Virus Hemagglutinin and Neuraminidase, but Not the Matrix Protein, Are Required for Assembly and Budding of Plasmid-Derived Virus-Like Particles , 2007, Journal of Virology.

[72]  H. Handa,et al.  Mechanism for inhibition of influenza virus RNA polymerase activity by matrix protein , 1996, Journal of virology.

[73]  J. Carrascosa,et al.  The Structure of a Biologically Active Influenza Virus Ribonucleoprotein Complex , 2009, PLoS pathogens.

[74]  B. Sodeik,et al.  Viral interactions with the cytoskeleton: a hitchhiker's guide to the cell , 2006, Cellular microbiology.

[75]  P. D’Eustachio,et al.  Identification and characterization of a human homolog of the Schizosaccharomyces pombe ras-like gene YPT-3. , 1991, Oncogene.

[76]  R. Gorelick,et al.  Nucleocapsid protein function in early infection processes. , 2008, Virus research.

[77]  M. Stevenson,et al.  Establishment of a Functional Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcription Complex Involves the Cytoskeleton , 1998, The Journal of experimental medicine.

[78]  P. Duesberg,et al.  Structure of the Ribonucleoprotein of Influenza Virus , 1972, Journal of virology.

[79]  O. Llorca,et al.  Structural and Functional Characterization of an Influenza Virus RNA Polymerase-Genomic RNA Complex , 2010, Journal of Virology.

[80]  T. Takimoto,et al.  Trafficking of Sendai Virus Nucleocapsids Is Mediated by Intracellular Vesicles , 2010, PloS one.

[81]  A. Kawaguchi,et al.  Involvement of vesicular trafficking system in membrane targeting of the progeny influenza virus genome. , 2010, Microbes and infection.

[82]  R. Compans,et al.  Respiratory syncytial virus matures at the apical surfaces of polarized epithelial cells , 1995, Journal of virology.

[83]  W. Britt,et al.  HCMV‐Encoded Glycoprotein M (UL100) Interacts with Rab11 Effector Protein FIP4 , 2009, Traffic.

[84]  P. Digard,et al.  Budding of filamentous and non-filamentous influenza A virus occurs via a VPS4 and VPS28-independent pathway. , 2009, Virology.

[85]  G. Blobel,et al.  Nuclear Import of Influenza Virus RNA Can Be Mediated by Viral Nucleoprotein and Transport Factors Required for Protein Import (*) , 1995, The Journal of Biological Chemistry.

[86]  K. Nakajima,et al.  Origin of small RNA in von Magnus particles of influenza virus , 1979, Journal of virology.

[87]  A. Helenius,et al.  Microtubule-mediated Transport of Incoming Herpes Simplex Virus 1 Capsids to the Nucleus , 1997, The Journal of cell biology.

[88]  J. Crowe,et al.  Apical recycling systems regulate directional budding of respiratory syncytial virus from polarized epithelial cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[89]  G. Hobom,et al.  The packaging signal of influenza viral RNA molecules. , 2001, RNA.

[90]  Andrew J. Lindsay,et al.  Crystal structure of rab11 in complex with rab11 family interacting protein 2. , 2006, Structure.

[91]  A. Cunningham,et al.  Axonal transport of herpes simplex virions to epidermal cells: evidence for a specialized mode of virus transport and assembly. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[92]  Michael J Rust,et al.  Visualizing infection of individual influenza viruses , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[93]  P. Bieniasz,et al.  Identification of Domains in Gag Important for Prototypic Foamy Virus Egress , 2005, Journal of Virology.

[94]  Grace E. Lee,et al.  Reconstitution of Herpes Simplex Virus Microtubule-Dependent Trafficking In Vitro , 2006, Journal of Virology.

[95]  Xianghong Jing,et al.  Influenza Virus M2 Protein Mediates ESCRT-Independent Membrane Scission , 2010, Cell.

[96]  D. Lambright,et al.  Structural basis for Rab11-mediated recruitment of FIP3 to recycling endosomes. , 2006, Journal of molecular biology.