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J Virol. Jun 1997; 71(6): 4679–4693.
PMCID: PMC191690

Poliovirus infection and expression of the poliovirus protein 2B provoke the disassembly of the Golgi complex, the organelle target for the antipoliovirus drug Ro-090179.


Infection of Vero cells with poliovirus results in complete disassembly of the Golgi complex. Milestones of the process of disassembly are the release to the cytosol of the beta-COP bound to Golgi membranes, the disruption of the cis-Golgi network into fragments scattered throughout the cytoplasm, and the disassembly of the stacked cisternae by a process mediated by long tubular structures. Transient expression of the viral protein 2B in COS-7 cells also causes the disassembly of the Golgi complex by a process preceded by the accumulation of the protein in the Golgi area. Vero cells infected for 3 h show no recognizable Golgi complexes at the ultrastructural level and display an enormously swollen endoplasmic reticulum (ER) with extensive areas of its surface heavily coated. Ro-090179 (Ro), a flavonoid isolated from the herb Agastache rugosa, provokes the specific swelling and disruption of the Golgi complex and strongly inhibits poliovirus infection. Ro provokes the swelling and the disruption of the stacked cisternae and trans-Golgi elements without affecting the cis-most Golgi cisternae much. Moreover, Ro inhibits the fusion of the Golgi complex with the ER in cells treated with brefeldin A and provokes the accumulation of the intermediate compartment membrane protein p58 into ERD2-positive Golgi elements but has no effect on the anterograde transport involved in protein secretion. Our results indicate that the secretory pathway and specifically the Golgi complex are preferential targets of poliovirus.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alcalde J, Bonay P, Roa A, Vilaro S, Sandoval IV. Assembly and disassembly of the Golgi complex: two processes arranged in a cis-trans direction. J Cell Biol. 1992 Jan;116(1):69–83. [PMC free article] [PubMed]
  • Alcalde J, Egea G, Sandoval IV. gp74 a membrane glycoprotein of the cis-Golgi network that cycles through the endoplasmic reticulum and intermediate compartment. J Cell Biol. 1994 Mar;124(5):649–665. [PMC free article] [PubMed]
  • Barco A, Carrasco L. A human virus protein, poliovirus protein 2BC, induces membrane proliferation and blocks the exocytic pathway in the yeast Saccharomyces cerevisiae. EMBO J. 1995 Jul 17;14(14):3349–3364. [PMC free article] [PubMed]
  • Barriocanal JG, Bonifacino JS, Yuan L, Sandoval IV. Biosynthesis, glycosylation, movement through the Golgi system, and transport to lysosomes by an N-linked carbohydrate-independent mechanism of three lysosomal integral membrane proteins. J Biol Chem. 1986 Dec 15;261(35):16755–16763. [PubMed]
  • Bienz K, Egger D, Wolff DA. Virus replication, cytopathology, and lysosomal enzyme response of mitotic and interphase Hep-2 cells infected with poliovirus. J Virol. 1973 Apr;11(4):565–574. [PMC free article] [PubMed]
  • Bienz K, Egger D, Rasser Y, Bossart W. Intracellular distribution of poliovirus proteins and the induction of virus-specific cytoplasmic structures. Virology. 1983 Nov;131(1):39–48. [PubMed]
  • Bienz K, Egger D, Pasamontes L. Association of polioviral proteins of the P2 genomic region with the viral replication complex and virus-induced membrane synthesis as visualized by electron microscopic immunocytochemistry and autoradiography. Virology. 1987 Sep;160(1):220–226. [PubMed]
  • Bienz K, Egger D, Pfister T, Troxler M. Structural and functional characterization of the poliovirus replication complex. J Virol. 1992 May;66(5):2740–2747. [PMC free article] [PubMed]
  • Bienz K, Egger D, Pfister T. Characteristics of the poliovirus replication complex. Arch Virol Suppl. 1994;9:147–157. [PubMed]
  • Bonifacino JS, Perez P, Klausner RD, Sandoval IV. Study of the transit of an integral membrane protein from secretory granules through the plasma membrane of secreting rat basophilic leukemia cells using a specific monoclonal antibody. J Cell Biol. 1986 Feb;102(2):516–522. [PMC free article] [PubMed]
  • Bonifacino JS, Yuan L, Sandoval IV. Internalization and recycling to serotonin-containing granules of the 80K integral membrane protein exposed on the surface of secreting rat basophilic leukaemia cells. J Cell Sci. 1989 Apr;92(Pt 4):701–712. [PubMed]
  • Caliguiri LA, Tamm I. Characterization of poliovirus-specific structures associated with cytoplasmic membranes. Virology. 1970 Sep;42(1):112–122. [PubMed]
  • Caliguiri LA, Tamm I. The role of cytoplasmic membranes in poliovirus biosynthesis. Virology. 1970 Sep;42(1):100–111. [PubMed]
  • Carrasco L. Picornavirus inhibitors. Pharmacol Ther. 1994;64(2):215–290. [PubMed]
  • Carrasco L. Modification of membrane permeability by animal viruses. Adv Virus Res. 1995;45:61–112. [PubMed]
  • Castrillo JL, Carrasco L. Action of 3-methylquercetin on poliovirus RNA replication. J Virol. 1987 Oct;61(10):3319–3321. [PMC free article] [PubMed]
  • Castrillo JL, Vanden Berghe D, Carrasco L. 3-Methylquercetin is a potent and selective inhibitor of poliovirus RNA synthesis. Virology. 1986 Jul 15;152(1):219–227. [PubMed]
  • Doedens JR, Kirkegaard K. Inhibition of cellular protein secretion by poliovirus proteins 2B and 3A. EMBO J. 1995 Mar 1;14(5):894–907. [PMC free article] [PubMed]
  • Donaldson JG, Lippincott-Schwartz J, Bloom GS, Kreis TE, Klausner RD. Dissociation of a 110-kD peripheral membrane protein from the Golgi apparatus is an early event in brefeldin A action. J Cell Biol. 1990 Dec;111(6 Pt 1):2295–2306. [PMC free article] [PubMed]
  • Donaldson JG, Finazzi D, Klausner RD. Brefeldin A inhibits Golgi membrane-catalysed exchange of guanine nucleotide onto ARF protein. Nature. 1992 Nov 26;360(6402):350–352. [PubMed]
  • Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7413–7417. [PMC free article] [PubMed]
  • Fujiwara T, Oda K, Yokota S, Takatsuki A, Ikehara Y. Brefeldin A causes disassembly of the Golgi complex and accumulation of secretory proteins in the endoplasmic reticulum. J Biol Chem. 1988 Dec 5;263(34):18545–18552. [PubMed]
  • Giachetti C, Hwang SS, Semler BL. cis-acting lesions targeted to the hydrophobic domain of a poliovirus membrane protein involved in RNA replication. J Virol. 1992 Oct;66(10):6045–6057. [PMC free article] [PubMed]
  • Giachetti C, Semler BL. Role of a viral membrane polypeptide in strand-specific initiation of poliovirus RNA synthesis. J Virol. 1991 May;65(5):2647–2654. [PMC free article] [PubMed]
  • Guinea R, Carrasco L. Phospholipid biosynthesis and poliovirus genome replication, two coupled phenomena. EMBO J. 1990 Jun;9(6):2011–2016. [PMC free article] [PubMed]
  • Helms JB, Rothman JE. Inhibition by brefeldin A of a Golgi membrane enzyme that catalyses exchange of guanine nucleotide bound to ARF. Nature. 1992 Nov 26;360(6402):352–354. [PubMed]
  • Irurzun A, Perez L, Carrasco L. Involvement of membrane traffic in the replication of poliovirus genomes: effects of brefeldin A. Virology. 1992 Nov;191(1):166–175. [PubMed]
  • Ishitsuka H, Ninomiya YT, Ohsawa C, Fujiu M, Suhara Y. Direct and specific inactivation of rhinovirus by chalcone Ro 09-0410. Antimicrob Agents Chemother. 1982 Oct;22(4):617–621. [PMC free article] [PubMed]
  • Ishitsuka H, Ohsawa C, Ohiwa T, Umeda I, Suhara Y. Antipicornavirus flavone Ro 09-0179. Antimicrob Agents Chemother. 1982 Oct;22(4):611–616. [PMC free article] [PubMed]
  • Johnson KL, Sarnow P. Three poliovirus 2B mutants exhibit noncomplementable defects in viral RNA amplification and display dosage-dependent dominance over wild-type poliovirus. J Virol. 1991 Aug;65(8):4341–4349. [PMC free article] [PubMed]
  • Lahtinen U, Dahllöf B, Saraste J. Characterization of a 58 kDa cis-Golgi protein in pancreatic exocrine cells. J Cell Sci. 1992 Oct;103(Pt 2):321–333. [PubMed]
  • Lenk R, Penman S. The cytoskeletal framework and poliovirus metabolism. Cell. 1979 Feb;16(2):289–301. [PubMed]
  • Lippincott-Schwartz J, Yuan LC, Bonifacino JS, Klausner RD. Rapid redistribution of Golgi proteins into the ER in cells treated with brefeldin A: evidence for membrane cycling from Golgi to ER. Cell. 1989 Mar 10;56(5):801–813. [PubMed]
  • Lippincott-Schwartz J, Donaldson JG, Schweizer A, Berger EG, Hauri HP, Yuan LC, Klausner RD. Microtubule-dependent retrograde transport of proteins into the ER in the presence of brefeldin A suggests an ER recycling pathway. Cell. 1990 Mar 9;60(5):821–836. [PubMed]
  • Maynell LA, Kirkegaard K, Klymkowsky MW. Inhibition of poliovirus RNA synthesis by brefeldin A. J Virol. 1992 Apr;66(4):1985–1994. [PMC free article] [PubMed]
  • Misumi Y, Misumi Y, Miki K, Takatsuki A, Tamura G, Ikehara Y. Novel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes. J Biol Chem. 1986 Aug 25;261(24):11398–11403. [PubMed]
  • Molla A, Paul AV, Wimmer E. Cell-free, de novo synthesis of poliovirus. Science. 1991 Dec 13;254(5038):1647–1651. [PubMed]
  • Orci L, Tagaya M, Amherdt M, Perrelet A, Donaldson JG, Lippincott-Schwartz J, Klausner RD, Rothman JE. Brefeldin A, a drug that blocks secretion, prevents the assembly of non-clathrin-coated buds on Golgi cisternae. Cell. 1991 Mar 22;64(6):1183–1195. [PubMed]
  • Pfister T, Pasamontes L, Troxler M, Egger D, Bienz K. Immunocytochemical localization of capsid-related particles in subcellular fractions of poliovirus-infected cells. Virology. 1992 Jun;188(2):676–684. [PubMed]
  • Rodríguez PL, Carrasco L. Poliovirus protein 2C has ATPase and GTPase activities. J Biol Chem. 1993 Apr 15;268(11):8105–8110. [PubMed]
  • Rothman JE. Mechanisms of intracellular protein transport. Nature. 1994 Nov 3;372(6501):55–63. [PubMed]
  • Saraste J, Palade GE, Farquhar MG. Temperature-sensitive steps in the transport of secretory proteins through the Golgi complex in exocrine pancreatic cells. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6425–6429. [PMC free article] [PubMed]
  • Saraste J, Svensson K. Distribution of the intermediate elements operating in ER to Golgi transport. J Cell Sci. 1991 Nov;100(Pt 3):415–430. [PubMed]
  • Schekman R, Orci L. Coat proteins and vesicle budding. Science. 1996 Mar 15;271(5255):1526–1533. [PubMed]
  • Schlegel A, Giddings TH, Jr, Ladinsky MS, Kirkegaard K. Cellular origin and ultrastructure of membranes induced during poliovirus infection. J Virol. 1996 Oct;70(10):6576–6588. [PMC free article] [PubMed]
  • Schweizer A, Fransen JA, Matter K, Kreis TE, Ginsel L, Hauri HP. Identification of an intermediate compartment involved in protein transport from endoplasmic reticulum to Golgi apparatus. Eur J Cell Biol. 1990 Dec;53(2):185–196. [PubMed]
  • Takegami T, Kuhn RJ, Anderson CW, Wimmer E. Membrane-dependent uridylylation of the genome-linked protein VPg of poliovirus. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7447–7451. [PMC free article] [PubMed]
  • Tang BL, Wong SH, Qi XL, Low SH, Hong W. Molecular cloning, characterization, subcellular localization and dynamics of p23, the mammalian KDEL receptor. J Cell Biol. 1993 Jan;120(2):325–338. [PMC free article] [PubMed]
  • Troxler M, Egger D, Pfister T, Bienz K. Intracellular localization of poliovirus RNA by in situ hybridization at the ultrastructural level using single-stranded riboprobes. Virology. 1992 Dec;191(2):687–697. [PubMed]
  • Turner JR, Tartakoff AM. The response of the Golgi complex to microtubule alterations: the roles of metabolic energy and membrane traffic in Golgi complex organization. J Cell Biol. 1989 Nov;109(5):2081–2088. [PMC free article] [PubMed]
  • Vega MA, Rodriguez F, Seguí B, Calés C, Alcalde J, Sandoval IV. Targeting of lysosomal integral membrane protein LIMP II. The tyrosine-lacking carboxyl cytoplasmic tail of LIMP II is sufficient for direct targeting to lysosomes. J Biol Chem. 1991 Sep 5;266(25):16269–16272. [PubMed]
  • Wehland J, Henkart M, Klausner R, Sandoval IV. Role of microtubules in the distribution of the Golgi apparatus: effect of taxol and microinjected anti-alpha-tubulin antibodies. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4286–4290. [PMC free article] [PubMed]
  • Wehland J, Sandoval IV. Cells injected with guanosine 5'-[alpha, beta-methylene]triphosphate, an alpha, beta-nonhydrolyzable analog of GTP, show anomalous patterns of tubulin polymerization affecting cell translocation, intracellular movement, and the organization of Golgi elements. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1938–1941. [PMC free article] [PubMed]
  • Wimmer E, Kuhn RJ, Pincus S, Yang CF, Toyoda H, Nicklin MJ, Takeda N. Molecular events leading to picornavirus genome replication. J Cell Sci Suppl. 1987;7:251–276. [PubMed]
  • Yuan L, Barriocanal JG, Bonifacino JS, Sandoval IV. Two integral membrane proteins located in the cis-middle and trans-part of the Golgi system acquire sialylated N-linked carbohydrates and display different turnovers and sensitivity to cAMP-dependent phosphorylation. J Cell Biol. 1987 Jul;105(1):215–227. [PMC free article] [PubMed]

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