Virus Movements on the Plasma Membrane Support Infection and Transmission between Cells

How viruses are transmitted across the mucosal epithelia of the respiratory, digestive, or excretory tracts, and how they spread from cell to cell and cause systemic infections, is incompletely understood. Recent advances from single virus tracking experiments have revealed conserved patterns of virus movements on the plasma membrane, including diffusive motions, drifting motions depending on retrograde flow of actin filaments or actin tail formation by polymerization, and confinement to submicrometer areas. Here, we discuss how viruses take advantage of cellular mechanisms that normally drive the movements of proteins and lipids on the cell surface. A concept emerges where short periods of fast diffusive motions allow viruses to rapidly move over several micrometers. Coupling to actin flow supports directional transport of virus particles during entry and cell-cell transmission, and local confinement coincides with either nonproductive stalling or infectious endocytic uptake. These conserved features of virus–host interactions upstream of infectious entry offer new perspectives for anti-viral interference.

[1]  K. Mikoshiba,et al.  L1-dependent neuritogenesis involves ankyrinB that mediates L1-CAM coupling with retrograde actin flow , 2003, The Journal of cell biology.

[2]  Daniel Choquet,et al.  Extracellular Matrix Rigidity Causes Strengthening of Integrin–Cytoskeleton Linkages , 1997, Cell.

[3]  Phoebe L Stewart,et al.  Cell integrins: commonly used receptors for diverse viral pathogens. , 2007, Trends in microbiology.

[4]  L. Norkin,et al.  Bound simian virus 40 translocates to caveolin-enriched membrane domains, and its entry is inhibited by drugs that selectively disrupt caveolae. , 1996, Molecular biology of the cell.

[5]  Francesca Santini,et al.  Spatial control of coated-pit dynamics in living cells , 1999, Nature Cell Biology.

[6]  Thilo Stehle,et al.  Structural basis of GM1 ganglioside recognition by simian virus 40 , 2008, Proceedings of the National Academy of Sciences.

[7]  M. Way,et al.  Signaling During Pathogen Infection , 2006, Science's STKE.

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

[9]  H. Selinka,et al.  Analysis of the infectious entry pathway of human papillomavirus type 33 pseudovirions. , 2002, Virology.

[10]  Y. Wang,et al.  Exchange of actin subunits at the leading edge of living fibroblasts: possible role of treadmilling , 1985, The Journal of cell biology.

[11]  Vahid Sandoghdar,et al.  Label-free optical detection and tracking of single virions bound to their receptors in supported membrane bilayers. , 2007, Nano letters.

[12]  E. Ikonen,et al.  Functional rafts in cell membranes , 1997, Nature.

[13]  P. Uchil,et al.  Retroviruses Human Immunodeficiency Virus and Murine Leukemia Virus Are Enriched in Phosphoinositides , 2008, Journal of Virology.

[14]  P. Cossart,et al.  Actin-based motility of vaccinia virus , 1995, Nature.

[15]  F. W. Denny The clinical impact of human respiratory virus infections. , 1995, American journal of respiratory and critical care medicine.

[16]  A. Valencia,et al.  Filamin-A regulates actin-dependent clustering of HIV receptors , 2007, Nature Cell Biology.

[17]  L. Pantanowitz,et al.  Imatinib-induced regression of AIDS-related Kaposi's sarcoma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  J. Kartenbeck,et al.  Major histocompatibility complex class I molecules mediate association of SV40 with caveolae. , 1997, Molecular biology of the cell.

[19]  H. Ewers,et al.  Ankyrin-Dependent and -Independent Mechanisms Orchestrate Axonal Compartmentalization of L1 Family Members Neurofascin and L1/Neuron–Glia Cell Adhesion Molecule , 2007, The Journal of Neuroscience.

[20]  Mario Schelhaas,et al.  Simian Virus 40 Depends on ER Protein Folding and Quality Control Factors for Entry into Host Cells , 2007, Cell.

[21]  R. Liddington,et al.  Structure of simian virus 40 at 3.8-Å resolution , 1991, Nature.

[22]  Feng Zhang,et al.  Assembly of endocytic machinery around individual influenza viruses during viral entry , 2004, Nature Structural &Molecular Biology.

[23]  Anne Imberty,et al.  N-Glycolyl GM 1 Ganglioside as a Receptor for Simian Virus 40 † , 2007 .

[24]  Thilo Stehle,et al.  Gangliosides are receptors for murine polyoma virus and SV40 , 2003, The EMBO journal.

[25]  Q. Sattentau,et al.  Avoiding the void: cell-to-cell spread of human viruses , 2008, Nature Reviews Microbiology.

[26]  L. Machesky Lamellipodia and filopodia in metastasis and invasion , 2008, FEBS letters.

[27]  Q. Sattentau,et al.  Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission , 2008, Nature Cell Biology.

[28]  H. Gerdes,et al.  Intercellular transfer mediated by tunneling nanotubes. , 2008, Current opinion in cell biology.

[29]  Anne Imberty,et al.  N-Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40 , 2007, Journal of Virology.

[30]  Dylan T Burnette,et al.  Myosin II functions in actin-bundle turnover in neuronal growth cones , 2006, Nature Cell Biology.

[31]  S. Shorte,et al.  Quantitative four-dimensional tracking of cytoplasmic and nuclear HIV-1 complexes , 2006, Nature Methods.

[32]  U. Greber,et al.  Junctional gating: the achilles' heel of epithelial cells in pathogen infection. , 2007, Cell host & microbe.

[33]  Marko Lampe,et al.  HIV-1–cellular interactions analyzed by single virus tracing , 2008, European Biophysics Journal.

[34]  X. Zhuang,et al.  Virus trafficking – learning from single-virus tracking , 2007, Nature Reviews Microbiology.

[35]  Petros Koumoutsakos,et al.  Single-particle tracking of murine polyoma virus-like particles on live cells and artificial membranes. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[36]  A. Helenius,et al.  Ganglioside‐dependent cell attachment and endocytosis of murine polyomavirus‐like particles , 2003, FEBS letters.

[37]  Akihiro Kusumi,et al.  Single-molecule tracking of membrane molecules: plasma membrane compartmentalization and dynamic assembly of raft-philic signaling molecules. , 2005, Seminars in immunology.

[38]  J. Bergelson,et al.  Virus-Induced Abl and Fyn Kinase Signals Permit Coxsackievirus Entry through Epithelial Tight Junctions , 2006, Cell.

[39]  H. Klenk,et al.  Human and avian influenza viruses target different cell types in cultures of human airway epithelium. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Akihiro Kusumi,et al.  Phospholipids undergo hop diffusion in compartmentalized cell membrane , 2002, The Journal of cell biology.

[41]  G. Danuser,et al.  Quantitative fluorescent speckle microscopy of cytoskeleton dynamics. , 2006, Annual review of biophysics and biomolecular structure.

[42]  J. Hoefs,et al.  Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group. , 1998, The New England journal of medicine.

[43]  Richard G. W. Anderson,et al.  Lipid rafts: at a crossroad between cell biology and physics , 2007, Nature Cell Biology.

[44]  Thilo Stehle,et al.  Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment , 1994, Nature.

[45]  Junichi Nakai,et al.  Vaccinia Virus Uses Macropinocytosis and Apoptotic Mimicry to Enter Host Cells , 2008 .

[46]  A. Luini,et al.  The closure of Pak1‐dependent macropinosomes requires the phosphorylation of CtBP1/BARS , 2008, The EMBO journal.

[47]  H. McMahon,et al.  Interactions , 2019, Mathematical Models in Science.

[48]  K. Jacobson,et al.  Detection of temporary lateral confinement of membrane proteins using single-particle tracking analysis. , 1995, Biophysical journal.

[49]  G. McFadden,et al.  Poxviruses and immune evasion. , 2003, Annual review of immunology.

[50]  M. Humphries,et al.  Synergistic control of cell adhesion by integrins and syndecans , 2007, Nature Reviews Molecular Cell Biology.

[51]  L. Dong,et al.  HIV Envelope-CXCR4 Signaling Activates Cofilin to Overcome Cortical Actin Restriction in Resting CD4 T Cells , 2008, Cell.

[52]  D. Hammer,et al.  Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow , 1995, Nature.

[53]  O. Weiland,et al.  Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C. Meta-analysis of individual patient data from European centers. , 1997, Journal of hepatology.

[54]  Simon C Watkins,et al.  A single common portal for clathrin-mediated endocytosis of distinct cargo governed by cargo-selective adaptors. , 2006, Molecular biology of the cell.

[55]  B. Druker,et al.  Kaposi's Sarcoma-Associated Herpesvirus-Induced Upregulation of the c-kit Proto-Oncogene, as Identified by Gene Expression Profiling, Is Essential for the Transformation of Endothelial Cells , 2002, Journal of Virology.

[56]  Ari Helenius,et al.  Human Papillomavirus Type 16 Entry: Retrograde Cell Surface Transport along Actin-Rich Protrusions , 2008, PLoS pathogens.

[57]  Michelle S. Longworth,et al.  Pathogenesis of Human Papillomaviruses in Differentiating Epithelia , 2004, Microbiology and Molecular Biology Reviews.

[58]  M. Kaksonen,et al.  Harnessing actin dynamics for clathrin-mediated endocytosis , 2006, Nature Reviews Molecular Cell Biology.

[59]  E. Reinherz,et al.  Antiviral chemotherapy facilitates control of poxvirus infections through inhibition of cellular signal transduction. , 2005, The Journal of clinical investigation.

[60]  R. Rueckert Picornaviridae: The viruses and their replication , 1996 .

[61]  P. Forscher,et al.  The Ig Superfamily Cell Adhesion Molecule, apCAM, Mediates Growth Cone Steering by Substrate–Cytoskeletal Coupling , 1998, The Journal of cell biology.

[62]  Akihiro Kusumi,et al.  Relationship of lipid rafts to transient confinement zones detected by single particle tracking. , 2002, Biophysical journal.

[63]  S. J. Smith,et al.  Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone , 1988, The Journal of cell biology.

[64]  P. Choyke,et al.  Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan , 2007, Nature Medicine.

[65]  M. Sheetz,et al.  Axonal transport: beyond kinesin and cytoplasmic dynein , 1991, Current Opinion in Neurobiology.

[66]  J. Bergelson,et al.  Coxsackievirus entry across epithelial tight junctions requires occludin and the small GTPases Rab34 and Rab5. , 2007, Cell host & microbe.

[67]  Urs F. Greber,et al.  Microtubule-dependent Plus- and Minus End–directed Motilities Are Competing Processes for Nuclear Targeting of Adenovirus , 1999, The Journal of cell biology.

[68]  M. Rao,et al.  Nanoclusters of GPI-Anchored Proteins Are Formed by Cortical Actin-Driven Activity , 2008, Cell.

[69]  M. Feinberg,et al.  Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases , 2005, Nature Medicine.

[70]  E. Kriehuber,et al.  Different Heparan Sulfate Proteoglycans Serve asCellular Receptors for HumanPapillomaviruses , 2003, Journal of Virology.

[71]  W. Greene,et al.  The Achilles Heel of the Trojan Horse Model of HIV-1 trans-Infection , 2008, PLoS pathogens.

[72]  Michael J Rust,et al.  Ligands for Clathrin-Mediated Endocytosis Are Differentially Sorted into Distinct Populations of Early Endosomes , 2006, Cell.

[73]  Clare Jolly,et al.  HIV-1 Cell to Cell Transfer across an Env-induced, Actin-dependent Synapse , 2004, The Journal of experimental medicine.

[74]  S Schleich,et al.  Entry of the two infectious forms of vaccinia virus at the plasma membane is signaling-dependent for the IMV but not the EEV. , 2000, Molecular biology of the cell.

[75]  F. Frischknecht,et al.  A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization , 2000, Nature Cell Biology.

[76]  Lucas Pelkmans,et al.  Local Actin Polymerization and Dynamin Recruitment in SV40-Induced Internalization of Caveolae , 2002, Science.

[77]  P. Koumoutsakos,et al.  Feature point tracking and trajectory analysis for video imaging in cell biology. , 2005, Journal of structural biology.

[78]  Michael J Rust,et al.  Dissecting the Cell Entry Pathway of Dengue Virus by Single-Particle Tracking in Living Cells , 2008, PLoS pathogens.

[79]  A L Pearlman,et al.  Extension of filopodia by motor-dependent actin assembly. , 1992, Cell motility and the cytoskeleton.

[80]  P. Liberali,et al.  Protein kinases: starting a molecular systems view of endocytosis. , 2008, Annual review of cell and developmental biology.

[81]  M. Kirschner,et al.  Cytoskeletal dynamics and nerve growth , 1988, Neuron.

[82]  T. Sakurai,et al.  MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site regulates neuronal growth. , 2006, Molecular biology of the cell.

[83]  P. Mattila,et al.  Filopodia: molecular architecture and cellular functions , 2008, Nature Reviews Molecular Cell Biology.

[84]  J. Heuser Deep-etch EM reveals that the early poxvirus envelope is a single membrane bilayer stabilized by a geodetic “honeycomb” surface coat , 2005, The Journal of cell biology.

[85]  J. Mercer,et al.  Subversion of CtBP1‐controlled macropinocytosis by human adenovirus serotype 3 , 2008, The EMBO journal.

[86]  Petros Koumoutsakos,et al.  A novel supervised trajectory segmentation algorithm identifies distinct types of human adenovirus motion in host cells. , 2007, Journal of structural biology.

[87]  F. Maxfield,et al.  Role of cholesterol and lipid organization in disease , 2005, Nature.

[88]  D. Hammer,et al.  Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow , 1995, Nature.

[89]  Akihiro Kusumi,et al.  Three-dimensional reconstruction of the membrane skeleton at the plasma membrane interface by electron tomography , 2006, The Journal of cell biology.

[90]  M. Zastrow,et al.  Cargo Regulates Clathrin-Coated Pit Dynamics , 2006, Cell.

[91]  R. Dwek,et al.  The Mannose Receptor Mediates Dengue Virus Infection of Macrophages , 2008, PLoS pathogens.

[92]  Mitsuhiro Osame,et al.  Spread of HTLV-I Between Lymphocytes by Virus-Induced Polarization of the Cytoskeleton , 2003, Science.

[93]  A. Helenius,et al.  Rab7 Associates with Early Endosomes to Mediate Sorting and Transport of Semliki Forest Virus to Late Endosomes , 2005, PLoS biology.

[94]  Lucas Pelkmans,et al.  Kinase-regulated quantal assemblies and kiss-and-run recycling of caveolae , 2005, Nature.

[95]  Nathan M Sherer,et al.  Cytonemes and tunneling nanotubules in cell-cell communication and viral pathogenesis. , 2008, Trends in cell biology.

[96]  J. Gilbert,et al.  Uptake Pathway of Polyomavirus via Ganglioside GD1a , 2004, Journal of Virology.

[97]  Gaudenz Danuser,et al.  Differential Transmission of Actin Motion Within Focal Adhesions , 2007, Science.

[98]  Kartik Chandran,et al.  Endocytosis by Random Initiation and Stabilization of Clathrin-Coated Pits , 2004, Cell.

[99]  T. Sakurai,et al.  Ankyrin binding mediates L1CAM interactions with static components of the cytoskeleton and inhibits retrograde movement of L1CAM on the cell surface , 2003, The Journal of cell biology.

[100]  H. Faden,et al.  Outbreak of adenovirus type 30 in a neonatal intensive care unit. , 2005, The Journal of pediatrics.

[101]  W. Mothes,et al.  Retroviruses can establish filopodial bridges for efficient cell-to-cell transmission , 2007, Nature Cell Biology.

[102]  Hans-Georg Kräusslich,et al.  The HIV lipidome: a raft with an unusual composition. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[103]  Christoph Peters,et al.  Cathepsin L and Cathepsin B Mediate Reovirus Disassembly in Murine Fibroblast Cells* , 2002, The Journal of Biological Chemistry.

[104]  Urs F. Greber,et al.  Infectious Adenovirus Type 2 Transport Through Early but not Late Endosomes , 2008, Traffic.

[105]  M. Bomsel,et al.  Entry of viruses through the epithelial barrier: pathogenic trickery , 2003, Nature Reviews Molecular Cell Biology.

[106]  Lucas Pelkmans,et al.  Clathrin- and caveolin-1–independent endocytosis , 2005, The Journal of cell biology.

[107]  Nathan M. Sherer,et al.  Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells , 2005, The Journal of cell biology.

[108]  L. Pelkmans,et al.  Assembly and trafficking of caveolar domains in the cell , 2005, The Journal of cell biology.

[109]  T. Schacker,et al.  HIV binding, penetration, and primary infection in human cervicovaginal tissue. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[110]  William R. Young,et al.  Strongly and weakly self-similar diffusion , 2001 .