title: Dynamics and restriction of murine leukemia virus cores in mitotic and interphase cells.
abstract: BACKGROUND
  Murine leukemia viruses (MLVs) naturally infect unsynchronized T and B lymphocytes, thus, the incoming virus encounters both interphase and mitotic cells. While it is well accepted that MLV requires cell division to complete its replication cycle, it is not known if ab initio infection of mitotic cells can result in productive infection. This question is highly relevant since the milieu of mitotic cells is markedly different from this of interphase cells; e.g. lacking radial microtubule network and intact nuclear envelope. To follow MLV infection in mitotic and interphase cells in real-time, we employed our recently developed infectious MLV particles with labeled cores, cellular models expressing fluorescence markers of different intracellular compartments and protocols for reversible mitotic arrest of MLV-susceptible cells.
  
  
  RESULTS
  Multi-wavelength live cell imaging was employed to simultaneously visualize GFP-labeled MLV cores, DiD-labeled viral or cellular membranes, and fluorescently-labeled microtubules or chromosomes. Cells were imaged either at interphase or upon mitotic arrest with microtubule poisons. Analysis of virus localization and trajectories revealed entry by endocytosis at interphase and mitosis, and correlation between viral mobility parameters and presence or absence of polymerized interphase microtubules. The success of infection of viruses that entered cells in mitosis was evidenced by their ability to reverse transcribe, their targeting to condensed chromosomes in the absence of radial microtubule network, and gene expression upon exit from mitosis. Comparison of infection by N, B or NB -tropic viruses in interphase and mitotic human cells revealed reduced restriction of the N-tropic virus, for infection initiated in mitosis.
  
  
  CONCLUSIONS
  The milieu of the mitotic cells supports all necessary requirements for early stages of MLV infection. Such milieu is suboptimal for restriction of N-tropic viruses, most likely by TRIM5α.
authors.affiliation: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. efi.elis@gmail.com.
authors.forename: Efrat
authors.initials: E
authors.lastname: Elis
authors.affiliation: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. marceloe@tauex.tau.ac.il.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ehrlich
authors.affiliation: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel. eranba@tauex.tau.ac.il.
authors.forename: Eran
authors.initials: E
authors.lastname: Bacharach
mesh_terms: D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002875:Chromosomes / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007399:Interphase; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008938:Mitosis; D041681:NIH 3T3 Cells; D009685:Nuclear Envelope / Q000821:virology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014771:Virion / Q000502:physiology* / Q000648:ultrastructure; D016662:Virus Integration; D014779:Virus Replication
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases