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2014 | 61 | 1 | 171-177
Article title

Changes in the mitochondrial network during ectromelia virus infection of permissive L929 cells

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Mitochondria are extremely important organelles in the life of a cell. Recent studies indicate that mitochondria also play a fundamental role in the cellular innate immune mechanisms against viral infections. Moreover, mitochondria are able to alter their shape continuously through fusion and fission. These tightly regulated processes are activated or inhibited under physiological or pathological (e.g. viral infection) conditions to help restore homeostasis. However, many types of viruses, such as orthopoxviruses, have developed various strategies to evade the mitochondrial-mediated antiviral innate immune responses. Moreover, orthopoxviruses exploit the mitochondria for their survival. Such viral activity has been reported during vaccinia virus (VACV) infection. Our study shows that the Moscow strain of ectromelia virus (ECTV-MOS), an orthopoxvirus, alters the mitochondrial network in permissive L929 cells. Upon infection, the branching structure of the mitochondrial network collapses and becomes disorganized followed by destruction of mitochondrial tubules during the late stage of infection. Small, discrete mitochondria co-localize with progeny virions, close to the cell membrane. Furthermore, clustering of mitochondria is observed around viral factories, particularly between the nucleus and viroplasm. Our findings suggest that ECTV-MOS modulates mitochondrial cellular distribution during later stages of the replication cycle, probably enabling viral replication and/or assembly as well as transport of progeny virions inside the cell. However, this requires further investigation.
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  • Division of Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Warszawa, Poland
  • Division of Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Warszawa, Poland
  • Division of Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Warszawa, Poland
  • Division of Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Warszawa, Poland
  • Division of Immunology, Department of Preclinical Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences - SGGW, Warszawa, Poland
  • Ahmad T, Aggarwal K, Pattnaik B, Mukherjee S, Sethi T, Tiwari BK, Kumar M, Micheal A, Mabalirajan U, Ghosh B, Sinha Roy S, Agrawal A (2013) Computational classification of mitochondrial shapes reflects stress and redox state. Cell Death Dis 4: e461.
  • Arnoult D (2007) Mitochondrial fragmentation in apoptosis. Trends Cell Biol 17: 6-12.
  • Benard G, Bellance N, James D, Parrone P, Fernandez H, Letellier T, Rossignol R (2007) Mitochondrial bioenergetics and structural network organization. J Cell Sci 120: 838-848.
  • Bereiter-Hahn J, Voth M (1994) Dynamics of mitochondria in living cells: shape changes, dislocations, fusion, and fission of mitochondria. Microsc Res Tech 27: 198-219.
  • Boldogh IR, Pon LA (2006) Interactions of mitochondria with the actin cytoskeleton. Biochim Biophys Acta 1763: 450-462.
  • Boratyńska A, Martyniszyn L, Szulc L, Krzyżowska M, Szczepanowska J, Niemiałtowski MG (2010) Contribution of rearranged actin structures to the spread of Ectromelia virus infection in vitro. Acta Virol 54: 41-48.
  • Bossy-Wetzel E, Barsoum MJ, Godzik A, Schwarzenbacher R, Lipton SA (2003) Mitochondrial fission in apoptosis, neurodegeneration and aging. CurrOpin Cell Biol 15: 706-716.
  • Chen RA, Ryzhakov G, Cooray S, Randow F, Smith GL (2008) Inhibition of IkappaB kinase by vaccinia virus virulence factor B14. PLoS Pathog 4: e22.
  • Deng L, Dai P, Parikh T, Cao H, Bhoj V, Sun Q, Chen Z, Merghoub T, Houghton A, Shuman S (2008) Vaccinia virus subverts a mitochondrial antiviral signaling protein-dependent innate immune response in keratinocytes through its double-stranded RNA binding protein, E3. J Virol 82: 10735-10746.
  • Everett H, Barry M, Lee SF, Sun XJ, Graham K, Stone J, Bleackley RC, McFadden G (2000) M11L: A novel mitochondria-localized protein of myxoma virus that blocks apoptosis in infected leukocytes. J Exp Med 191: 1487-1498.
  • Fenner F (2000) Adventures with poxviruses of vertebrates. FEMS Microbiol Rev 24: 123-133.
  • Gomes LC, Di Benedetto G, Scorrano L (2011) During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol 13: 589-598.
  • Guzun R, Karu-Varikmaa M, Gonzalez-Granillo M, Kuznetsov AV, Michel L, Cottet-Rousselle C, Saaremäe M, Kaambre T, Metsis M, Grimm M, Auffray C, Saks V (2011) Mitochondria-cytoskeleton interaction: distribution of β-tubulins in cardiomyocytes and HL-1 cells. BiochimBiophys Acta 1807: 458-469.
  • Heath CM, Windsor M, Wileman T (2001) Aggresomes resemble sites specialized for virus assembly. J Cell Biol 153: 449-455.
  • Hollenbeck PJ, Saxton WM (2005) The axonal transport of mitochondria. J Cell Sci 118: 5411-5419.
  • Ishikawa H, Barber GN (2008) STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455: 674-678.
  • Kim S, Kim HY, Lee S, Kim SW, Sohn S, Kim K, Cho H (2007) Hepatitis B virus x protein induces perinuclear mitochondrial clustering in microtubule- and dynein-dependent manners. J Virol 81: 1714-1726.
  • Krzyżowska M, Schollenberger A, Skierski J, Niemiałtowski M (2002) Apoptosis during ectromelia orthopoxvirus infection is DEVDase dependent: in vitro and in vivo studies. Microbes Infect 4: 599-611.
  • Ligon LA, Steward O (2000) Role of microtubules and actin filaments in the movement of mitochondria in the axons and dendrites of cultured hippocampal neurons. J Comp Neurol 427: 351-361.
  • Liu X, Hajnóczky G (2011) Altered fusion dynamics underlie unique morphological changes in mitochondria during hypoxia-reoxygenation stress. Cell Death Differ 18: 1561-1572.
  • Lynn H, Horsington J, Ter LK, Han S, Chew YL, Diefenbach RJ, Way M, Chaudhri G, Karupiah G, Newsome TP (2012) Loss of cytoskeletal transport during egress critically attenuates ectromelia virus infection in vivo. J Virol 86: 7427-7443.
  • Mazzon M, Peters NE, Loenarz C, Krysztofinska EM, Ember SW, Ferguson BJ, Smith GL (2013) A mechanism for induction of a hypoxic response by vaccinia virus. Proc Natl Acad Sci USA 110: 12444-12449.
  • McFadden G (2005) Poxvirus tropism. Nat Rev Microbiol 3: 201-213.
  • Melo-Silva CR, Tscharke DC, Lobigs M, Koskinen A, Wong YC, Buller RM, Müllbacher A, Regner M (2011) The ectromelia virus SPI-2 protein causes lethal mousepox by preventing NK cell responses. J Virol 85: 11170-11182.
  • Morris RL, Hollenbeck PJ (1995) Axonal transport of mitochondria along microtubules and Factin in living vertebrate neurons. J Cell Biol 131: 1315-1326.
  • Nomura-Takigawa Y, Nagano-Fujii M, Deng L, Kitazawa S, Ishido S, Sada K, Hotta H (2006) Non-structural protein 4A of hepatitis C virus accumulates on mitochondria and renders the cells prone to undergoing mitochondria-mediated apoptosis. J Gen Virol 87: 1935-1945.
  • Risco C, Rodríguez JR, López-Iglesias C, Carrascosa JL, Esteban M, Rodríguez D (2002) Endoplasmic reticulum-Golgi intermediate compartment membranes and vimentin filaments participate in vaccinia virus assembly. J Virol 76: 1839-1855.
  • Rojo G, Chamorro M, Salas ML, Vinuela E, Cuezva JM, Salas J (1998) Migration of mitochondria to viral assembly sites in african swine fever virus-infected cells. J Virol 72: 7583-7588.
  • Schepis A, Schramm B, de Haan CA, Locker JK (2006) Vaccinia virus-induced microtubule-dependent cellular rearrangements. Traffic 7: 308-323.
  • Seth RB, Sun L, Chen ZJ (2006) Antiviral innate immunity pathways.Cell Res 16: 141-147.
  • Tait SW, Green DR (2010) Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol 11: 621-632.
  • Tolonen N, Doglio L, Schleich S, Krijnse Locker J (2001) Vaccinia virus DNA replication occurs in endoplasmic reticulum-enclosed cytoplasmic mini-nuclei. Mol Biol Cell 12: 2031-2046.
  • Wasilenko ST, Stewart TL, Meyers AF, Barry M (2003) Vaccinia virus encodes a previously uncharacterized mitochondrial-associated inhibitor of apoptosis. Proc Natl Acad Sci 100: 14345-14350.
  • Wasilewski M, Scorrano L (2009) The changing shape of mitochondrial apoptosis. Trends Endocrinol Metab 20: 287-294.
  • Varadi A, Johnson-Cadwell LI, Cirulli V, Yoon Y, Allan VJ, Rutter GA (2004) Cytoplasmic dynein regulates the subcellular distribution of mitochondria by controlling the recruitment of the fission factor dynamin-related protein-1. J Cell Sci 117: 4389-4400.
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