Viral stop-and-go along microtubules: taking a ride with dynein and kinesins.

Incoming viral particles move from the cell surface to sites of viral transcription and replication. By contrast, during assembly and egress, subviral nucleoprotein complexes and virions travel back to the plasma membrane. Because diffusion of large molecules is severely restricted in the cytoplasm, viruses use ATP-hydrolyzing molecular motors of the host for propelling along the microtubules, which are the intracellular highways. Recent studies have revealed that, besides travelling inside endocytic or exocytic vesicles, viral proteins interact directly with dynein or kinesin motors. Understanding the molecular mechanisms of cytoplasmic viral transport will aid in the construction of viral vectors for human gene therapy and the search for new antiviral targets.

[1]  Geoffrey L. Smith,et al.  The vaccinia virus A27L protein is needed for the microtubule-dependent transport of intracellular mature virus particles. , 2000, The Journal of general virology.

[2]  E. Bon,et al.  HIV-1 integrase interacts with yeast microtubule-associated proteins. , 2002, Biochimica et biophysica acta.

[3]  T. Newsome,et al.  Src Mediates a Switch from Microtubule- to Actin-Based Motility of Vaccinia Virus , 2004, Science.

[4]  R. Diefenbach,et al.  Herpes Simplex Virus Tegument Protein US11 Interacts with Conventional Kinesin Heavy Chain , 2002, Journal of Virology.

[5]  L. Enquist,et al.  Local modulation of plus-end transport targets herpesvirus entry and egress in sensory axons. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  B. Sodeik Unchain my heart, baby let me go—the entry and intracellular transport of HIV , 2002, The Journal of cell biology.

[7]  F. Grosveld,et al.  Baculovirus Infection of Nondividing Mammalian Cells: Mechanisms of Entry and Nuclear Transport of Capsids , 2001, Journal of Virology.

[8]  H. Raux,et al.  Interaction of the Rabies Virus P Protein with the LC8 Dynein Light Chain , 2000, Journal of Virology.

[9]  E. Réal,et al.  Targeting of incoming retroviral Gag to the centrosome involves a direct interaction with the dynein light chain 8 , 2003, Journal of Cell Science.

[10]  Elaine Fuchs,et al.  Coordinating cytoskeletal tracks to polarize cellular movements , 2004, The Journal of cell biology.

[11]  M. Vihinen-Ranta,et al.  Exploitation of Microtubule Cytoskeleton and Dynein during Parvoviral Traffic toward the Nucleus , 2003, Journal of Virology.

[12]  Mark J. Schnitzer,et al.  Kinesin hydrolyses one ATP per 8-nm step , 1997, Nature.

[13]  M. Fornerod,et al.  Nuclear import in viral infections. , 2005, Current topics in microbiology and immunology.

[14]  S. Deacon,et al.  Motor-cargo interactions: the key to transport specificity. , 2002, Trends in cell biology.

[15]  K. Kirkegaard,et al.  Cellular autophagy: surrender, avoidance and subversion by microorganisms , 2004, Nature Reviews Microbiology.

[16]  G. Kreitzer,et al.  Dynein- and microtubule-mediated translocation of adenovirus serotype 5 occurs after endosomal lysis. , 2000, Human gene therapy.

[17]  N. Jouvenet,et al.  African swine fever virus infection disrupts centrosome assembly and function. , 2005, The Journal of general virology.

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

[19]  M. Horwitz,et al.  An Adenovirus Inhibitor of Tumor Necrosis Factor Alpha-Induced Apoptosis Complexes with Dynein and a Small GTPase , 2000, Journal of Virology.

[20]  M. Law,et al.  Vaccinia virus cores are transported on microtubules. , 2003, The Journal of general virology.

[21]  L. Dixon,et al.  The African swine fever virus dynein‐binding protein p54 induces infected cell apoptosis , 2004, FEBS letters.

[22]  K. Oegema,et al.  The minus end in sight , 2003, Current Biology.

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

[24]  I. Mohr NEUTRALIZING INNATE HOST DEFENSES TO CONTROL VIRAL TRANSLATION IN HSV-1 INFECTED CELLS , 2004, International reviews of immunology.

[25]  B. Sodeik,et al.  The role of the cytoskeleton during viral infection. , 2005, Current topics in microbiology and immunology.

[26]  S. Kuge,et al.  Receptor (CD155)-Dependent Endocytosis of Poliovirus and Retrograde Axonal Transport of the Endosome , 2004, Journal of Virology.

[27]  J. Carson,et al.  RNA Trafficking Signals in Human Immunodeficiency Virus Type 1 , 2001, Molecular and Cellular Biology.

[28]  J. Krijnse Locker,et al.  Microtubule-dependent organization of vaccinia virus core-derived early mRNAs into distinct cytoplasmic structures. , 2001, Molecular biology of the cell.

[29]  K. Luby-Phelps,et al.  Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area. , 2000, International review of cytology.

[30]  I. Vernos,et al.  Dynactin is required for bidirectional organelle transport , 2003, The Journal of cell biology.

[31]  E. Wimmer,et al.  Interaction of the Poliovirus Receptor CD155 with the Dynein Light Chain Tctex-1 and Its Implication for Poliovirus Pathogenesis* , 2002, The Journal of Biological Chemistry.

[32]  E. Réal,et al.  Molecular basis for the interaction between rabies virus phosphoprotein P and the dynein light chain LC8: dissociation of dynein-binding properties and transcriptional functionality of P. , 2001, The Journal of general virology.

[33]  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.

[34]  R. Crystal,et al.  Cytoplasmic Dynein Mediates Adenovirus Binding to Microtubules , 2004, Journal of Virology.

[35]  C. Echeverri,et al.  Function of dynein and dynactin in herpes simplex virus capsid transport. , 2002, Molecular biology of the cell.

[36]  T. Wileman,et al.  Aggresomes Resemble Sites Specialized for Virus Assembly , 2001, The Journal of cell biology.

[37]  A. Strasser,et al.  Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more. , 2003, Annual review of immunology.

[38]  G. Kannourakis,et al.  A time to kill: viral manipulation of the cell death program. , 2002, The Journal of general virology.

[39]  K. Tanaka,et al.  Microtubule Network Facilitates Nuclear Targeting of Human Cytomegalovirus Capsid , 2003, Journal of Virology.

[40]  S. Pimplikar,et al.  PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[41]  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.

[42]  K. Verhey Motors and Membrane Trafficking , 2004 .

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

[44]  Brent J. Ryckman,et al.  Ultrastructural Localization of the Herpes Simplex Virus Type 1 UL31, UL34, and US3 Proteins Suggests Specific Roles in Primary Envelopment and Egress of Nucleocapsids , 2002, Journal of Virology.

[45]  M. Way,et al.  Transport of African Swine Fever Virus from Assembly Sites to the Plasma Membrane Is Dependent on Microtubules and Conventional Kinesin , 2004, Journal of Virology.

[46]  E. Hunter,et al.  M‐PMV Capsid Transport Is Mediated by Env/Gag Interactions at the Pericentriolar Recycling Endosome , 2003, Traffic.

[47]  M. Hallek,et al.  Real-Time Single-Molecule Imaging of the Infection Pathway of an Adeno-Associated Virus , 2001, Science.

[48]  H. Will,et al.  Itinerary of Hepatitis B Viruses: Delineation of Restriction Points Critical for Infectious Entry , 2004, Journal of Virology.

[49]  Nobutaka Hirokawa,et al.  Molecular motors and mechanisms of directional transport in neurons , 2005, Nature Reviews Neuroscience.

[50]  B. C. Carter,et al.  Cytoplasmic dynein functions as a gear in response to load , 2004, Nature.

[51]  I. Mohr,et al.  Association of the Herpes Simplex Virus Type 1 Us11 Gene Product with the Cellular Kinesin Light-Chain-Related Protein PAT1 Results in the Redistribution of Both Polypeptides , 2003, Journal of Virology.

[52]  P. Desai,et al.  Herpes simplex virus type 1 VP26 is not essential for replication in cell culture but influences production of infectious virus in the nervous system of infected mice. , 1998, Virology.

[53]  E. Sztul,et al.  Hassles with Taking Out the Garbage: Aggravating Aggresomes , 2002, Traffic.

[54]  Y. Stierhof,et al.  Human Cytomegalovirus Labeled with Green Fluorescent Protein for Live Analysis of Intracellular Particle Movements , 2005, Journal of Virology.

[55]  L. Enquist,et al.  Break ins and break outs: viral interactions with the cytoskeleton of Mammalian cells. , 2002, Annual review of cell and developmental biology.

[56]  E. Holzbaur,et al.  A Direct Interaction between Cytoplasmic Dynein and Kinesin I May Coordinate Motor Activity* , 2004, Journal of Biological Chemistry.

[57]  R. Kopito,et al.  Aggresomes, inclusion bodies and protein aggregation. , 2000, Trends in cell biology.

[58]  M. Koltzenburg,et al.  Axoplasmic Importins Enable Retrograde Injury Signaling in Lesioned Nerve , 2003, Neuron.

[59]  J. Lavail,et al.  Retrograde axonal transport of herpes simplex virus: evidence for a single mechanism and a role for tegument. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[60]  E. Nogales Structural insights into microtubule function. , 2000, Annual review of biochemistry.

[61]  N. Tordo,et al.  Cytoplasmic Dynein LC8 Interacts with Lyssavirus Phosphoprotein , 2000, Journal of Virology.

[62]  U. Greber,et al.  Adenovirus‐activated PKA and p38/MAPK pathways boost microtubule‐mediated nuclear targeting of virus , 2001, The EMBO journal.

[63]  M. Welte,et al.  Bidirectional Transport along Microtubules , 2004, Current Biology.

[64]  K. Byth,et al.  Herpes Simplex Virus Type 1 Capsid Protein VP26 Interacts with Dynein Light Chains RP3 and Tctex1 and Plays a Role in Retrograde Cellular Transport* , 2004, Journal of Biological Chemistry.

[65]  D. McDonald,et al.  Visualization of the intracellular behavior of HIV in living cells , 2002, The Journal of cell biology.

[66]  P. Ortiz de Montellano,et al.  Identification of novel cellular proteins that bind to the LC8 dynein light chain using a pepscan technique , 2001, FEBS letters.

[67]  M. Way,et al.  Viral transport and the cytoskeleton , 2001, Current Opinion in Cell Biology.

[68]  Y. Kawaguchi,et al.  Herpes simplex virus type 2 membrane protein UL56 associates with the kinesin motor protein KIF1A. , 2005, The Journal of general virology.

[69]  C. Amici,et al.  NEW EMBO MEMBER’S REVIEW: NF-κB and virus infection: who controls whom , 2003 .

[70]  V. Allan,et al.  Apoptotic Cleavage of Cytoplasmic Dynein Intermediate Chain and P150GluedStops Dynein-Dependent Membrane Motility , 2001, The Journal of cell biology.

[71]  N. Hirokawa,et al.  Binding of Murine Leukemia Virus Gag Polyproteins to KIF4, a Microtubule-Based Motor Protein , 1998, Journal of Virology.

[72]  J. Albar,et al.  Recognition of novel viral sequences that associate with the dynein light chain LC8 identified through a pepscan technique , 2003, FEBS letters.

[73]  S. Goff,et al.  Cellular Motor Protein KIF-4 Associates with Retroviral Gag , 1999, Journal of Virology.

[74]  Anthony A. Hyman,et al.  Dynamics and mechanics of the microtubule plus end , 2022 .

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

[76]  R. Vallee,et al.  Dynein: An ancient motor protein involved in multiple modes of transport. , 2004, Journal of neurobiology.

[77]  B. Moss,et al.  Vaccinia Virus A36R Membrane Protein Provides a Direct Link between Intracellular Enveloped Virions and the Microtubule Motor Kinesin , 2004, Journal of Virology.

[78]  L. Pomeranz,et al.  Microtubule Reorganization during Herpes Simplex Virus Type 1 Infection Facilitates the Nuclear Localization of VP22, a Major Virion Tegument Protein , 2001, Journal of Virology.

[79]  M. Willard Rapid Directional Translocations in Virus Replication , 2002, Journal of Virology.

[80]  Steven P. Gross,et al.  Herpesviruses use bidirectional fast-axonal transport to spread in sensory neurons , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[81]  R. Vallee,et al.  The Herpes Simplex Virus 1 UL34 Protein Interacts with a Cytoplasmic Dynein Intermediate Chain and Targets Nuclear Membrane , 2000, Journal of Virology.

[82]  Steven P. Gross,et al.  Molecular Motors: Strategies to Get Along , 2004, Current Biology.

[83]  Anne Müsch,et al.  Microtubule Organization and Function in Epithelial Cells , 2004, Traffic.

[84]  L. Dixon,et al.  African Swine Fever Virus Protein p54 Interacts with the Microtubular Motor Complex through Direct Binding to Light-Chain Dynein , 2001, Journal of Virology.

[85]  Hongwei Wu,et al.  Solution structure of the Tctex1 dimer reveals a mechanism for dynein-cargo interactions. , 2005, Structure.

[86]  Masahide Kikkawa,et al.  Dynein and kinesin share an overlapping microtubule‐binding site , 2004, The EMBO journal.

[87]  Lucas Pelkmans,et al.  Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER , 2001, Nature Cell Biology.