1887

Abstract

Infections with dengue virus (DENV) are a significant public health concern in tropical and subtropical regions. However, little detail is known about how DENV interacts with the host-cell machinery to facilitate its translation and replication. In DENV-infected HepG2 cells, an increase in the level of LC3-II (microtubule-associated protein 1 light chain 3 form II), the autophagosomal membrane-bound form of LC3, was observed, and LC3 was found to co-localize with dsRNA and DENV NS1 protein, as well as ribosomal protein L28, indicating the presence of at least some of the DENV translation/replication machinery on autophagic vacuoles. Inhibition of fusion of autophagic vacuoles with lysosomes resulted in an increase in both intracellular and extracellular virus, and co-localization observed between mannose-6-phosphate receptor (MPR) and dsRNA and between MPR and LC3 identified the autophagic vacuoles as amphisomes. Amphisomes are formed as a result of fusion between endosomal and autophagic vacuoles, and as such provide a direct link between virus entry and subsequent replication and translation.

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2009-02-01
2024-04-19
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References

  1. Abramoff M. D., Magelhaes P. J., Ram S. J. 2004; Image processing with ImageJ. Biophotonics International 11:36–42
    [Google Scholar]
  2. Allison S. L., Schalich J., Stiasny K., Mandl C. W., Kunz C., Heinz F. X. 1995; Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH. J Virol 69:695–700
    [Google Scholar]
  3. Bampton E. T., Goemans C. G., Niranjan D., Mizushima N., Tolkovsky A. M. 2005; The dynamics of autophagy visualized in live cells: from autophagosome formation to fusion with endo/lysosomes. Autophagy 1:23–36 [CrossRef]
    [Google Scholar]
  4. Boulton R. W., Westaway E. G. 1976; Replication of the flavivirus Kunjin: proteins, glycoproteins, and maturation associated with cell membranes. Virology 69:416–430 [CrossRef]
    [Google Scholar]
  5. Cahour A., Falgout B., Lai C. J. 1992; Cleavage of the dengue virus polyprotein at the NS3/NS4A and NS4B/NS5 junctions is mediated by viral protease NS2B–NS3, whereas NS4A/NS4B may be processed by a cellular protease. J Virol 66:1535–1542
    [Google Scholar]
  6. Chang G. J. 1997; Molecular biology of dengue viruses. In Dengue and Dengue Hemorrhagic Fever . pp 175–198Edited by Gubler D. J., Kuno G. Wallingford: CAB International;
  7. Clyde K., Kyle J. L., Harris E. 2006; Recent advances in deciphering viral and host determinants of dengue virus replication and pathogenesis. J Virol 80:11418–11431 [CrossRef]
    [Google Scholar]
  8. Dunn W. A. Jr 1990a; Studies on the mechanisms of autophagy: formation of the autophagic vacuole. J Cell Biol 110:1923–1933 [CrossRef]
    [Google Scholar]
  9. Dunn W. A. Jr 1990b; Studies on the mechanisms of autophagy: maturation of the autophagic vacuole. J Cell Biol 110:1935–1945 [CrossRef]
    [Google Scholar]
  10. French A. P., Mills S., Swarup R., Bennett M. J., Pridmore T. P. 2008; Colocalization of fluorescent markers in confocal microscope images of plant cells. Nat Protoc 3:619–628 [CrossRef]
    [Google Scholar]
  11. Gordon P. B., Seglen P. O. 1988; Prelysosomal convergence of autophagic and endocytic pathways. Biochem Biophys Res Commun 151:40–47 [CrossRef]
    [Google Scholar]
  12. Gordon P. B., Hoyvik H., Seglen P. O. 1992; Prelysosomal and lysosomal connections between autophagy and endocytosis. Biochem J 283:361–369
    [Google Scholar]
  13. Guzman M. G., Kouri G. 2002; Dengue: an update. Lancet Infect Dis 2:33–42 [CrossRef]
    [Google Scholar]
  14. Hanada T., Noda N. N., Satomi Y., Ichimura Y., Fujioka Y., Takao T., Inagaki F., Ohsumi Y. 2007; The Atg12–Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem 282:37298–37302 [CrossRef]
    [Google Scholar]
  15. Heinz F. X., Stiasny K., Allison S. L. 2004; The entry machinery of flaviviruses. Arch Virol Suppl 18:133–137
    [Google Scholar]
  16. Jackson W. T., Giddings T. H. Jr, Taylor M. P., Mulinyawe S., Rabinovitch M., Kopito R. R., Kirkegaard K. 2005; Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol 3:e156 [CrossRef]
    [Google Scholar]
  17. Kabeya Y., Mizushima N., Ueno T., Yamamoto A., Kirisako T., Noda T., Kominami E., Ohsumi Y., Yoshimori T. 2000; LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728 [CrossRef]
    [Google Scholar]
  18. Kihara A., Kabeya Y., Ohsumi Y., Yoshimori T. 2001; Beclin–phosphatidylinositol 3-kinase complex functions at the trans -Golgi network. EMBO Rep 2:330–335 [CrossRef]
    [Google Scholar]
  19. Kim J., Huang W. P., Stromhaug P. E., Klionsky D. J. 2002; Convergence of multiple autophagy and cytoplasm to vacuole targeting components to a perivacuolar membrane compartment prior to de novo vesicle formation. J Biol Chem 277:763–773 [CrossRef]
    [Google Scholar]
  20. Kimura S., Noda T., Yoshimori T. 2007; Dissection of the autophagosome maturation process by a novel reporter protein, tandem fluorescent-tagged LC3. Autophagy 3:452–460 [CrossRef]
    [Google Scholar]
  21. Krishnan M. N., Sukumaran B., Pal U., Agaisse H., Murray J. L., Hodge T. W., Fikrig E. 2007; Rab 5 is required for the cellular entry of dengue and West Nile viruses. J Virol 81:4881–4885 [CrossRef]
    [Google Scholar]
  22. Lee H. K., Iwasaki A. 2008; Autophagy and antiviral immunity. Curr Opin Immunol 20:23–29 [CrossRef]
    [Google Scholar]
  23. Lee Y. R., Lei H. Y., Liu M. T., Wang J. R., Chen S. H., Jiang-Shieh Y. F., Lin Y. S., Yeh T. M., Liu C. C., Liu H. S. 2008; Autophagic machinery activated by dengue virus enhances virus replication. Virology 374:240–248 [CrossRef]
    [Google Scholar]
  24. Lerena C., Calligaris S. D., Colombo M. I. 2008; Autophagy: for better or for worse, in good times or in bad times. Curr Mol Med 8:92–101 [CrossRef]
    [Google Scholar]
  25. Levine B., Klionsky D. J. 2004; Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6:463–477 [CrossRef]
    [Google Scholar]
  26. Mackenzie J. M., Jones M. K., Young P. R. 1996; Immunolocalization of the dengue virus nonstructural glycoprotein NS1 suggests a role in viral RNA replication. Virology 220:232–240 [CrossRef]
    [Google Scholar]
  27. Malavige G. N., Fernando S., Fernando D. J., Seneviratne S. L. 2004; Dengue viral infections. Postgrad Med J 80:588–601 [CrossRef]
    [Google Scholar]
  28. Meijer A. J., Codogno P. 2006; Signalling and autophagy regulation in health, aging and disease. Mol Aspects Med 27:411–425 [CrossRef]
    [Google Scholar]
  29. Miller S., Krijnse-Locker J. 2008; Modification of intracellular membrane structures for virus replication. Nat Rev Microbiol 6:363–374 [CrossRef]
    [Google Scholar]
  30. Mizushima N., Noda T., Yoshimori T., Tanaka Y., Ishii T., George M. D., Klionsky D. J., Ohsumi M., Ohsumi Y. 1998; A protein conjugation system essential for autophagy. Nature 395:395–398 [CrossRef]
    [Google Scholar]
  31. Mizushima N., Yoshimori T., Ohsumi Y. 2002; Mouse Apg10 as an Apg12-conjugating enzyme: analysis by the conjugation-mediated yeast two-hybrid method. FEBS Lett 532:450–454 [CrossRef]
    [Google Scholar]
  32. Mizushima N., Levine B., Cuervo A. M., Klionsky D. J. 2008; Autophagy fights disease through cellular self-digestion. Nature 451:1069–1075 [CrossRef]
    [Google Scholar]
  33. Modis Y., Ogata S., Clements D., Harrison S. C. 2004; Structure of the dengue virus envelope protein after membrane fusion. Nature 427:313–319 [CrossRef]
    [Google Scholar]
  34. Mukhopadhyay S., Kuhn R. J., Rossmann M. G. 2005; A structural perspective of the flavivirus life cycle. Nat Rev Microbiol 3:13–22 [CrossRef]
    [Google Scholar]
  35. Noda T., Ohsumi Y. 1998; Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 273:3963–3966 [CrossRef]
    [Google Scholar]
  36. Ohsumi Y. 2001; Molecular dissection of autophagy: two ubiquitin-like systems. Nat Rev Mol Cell Biol 2:211–216 [CrossRef]
    [Google Scholar]
  37. Pedersen K. W., van der Meer Y., Roos N., Snijder E. J. 1999; Open reading frame 1a-encoded subunits of the arterivirus replicase induce endoplasmic reticulum-derived double-membrane vesicles which carry the viral replication complex. J Virol 73:2016–2026
    [Google Scholar]
  38. Puttikhunt C., Kasinrerk W., Srisa-ad S., Duangchinda T., Silakate W., Moonsom S., Sittisombut N., Malasit P. 2003; Production of anti-dengue NS1 monoclonal antibodies by DNA immunization. J Virol Methods 109:55–61 [CrossRef]
    [Google Scholar]
  39. Salonen A., Ahola T., Kaariainen L. 2005; Viral RNA replication in association with cellular membranes. Curr Top Microbiol Immunol 285:139–173
    [Google Scholar]
  40. Seglen P. O., Gordon P. B. 1982; 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci U S A 79:1889–1892 [CrossRef]
    [Google Scholar]
  41. Sithisarn P., Suksanpaisan L., Thepparit C., Smith D. R. 2003; Behavior of the dengue virus in solution. J Med Virol 71:532–539 [CrossRef]
    [Google Scholar]
  42. Thepparit C., Smith D. R. 2004; Serotype-specific entry of dengue virus into liver cells: identification of the 37-kilodalton/67-kilodalton high-affinity laminin receptor as a dengue virus serotype 1 receptor. J Virol 78:12647–12656 [CrossRef]
    [Google Scholar]
  43. van der Schaar H. M., Rust M. J., Waarts B. L., van der Ende-Metselaar H., Kuhn R. J., Wilschut J., Zhuang X., Smit J. M. 2007; Characterization of the early events in dengue virus cell entry by biochemical assays and single-virus tracking. J Virol 81:12019–12028 [CrossRef]
    [Google Scholar]
  44. Weber F., Wagner V., Rasmussen S. B., Hartmann R., Paludan S. R. 2006; Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses. J Virol 80:5059–5064 [CrossRef]
    [Google Scholar]
  45. Xie Z., Klionsky D. J. 2007; Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9:1102–1109 [CrossRef]
    [Google Scholar]
  46. Yoshii K., Konno A., Goto A., Nio J., Obara M., Ueki T., Hayasaka D., Mizutani T., Kariwa H., Takashima I. 2004; Single point mutation in tick-borne encephalitis virus prM protein induces a reduction of virus particle secretion. J Gen Virol 85:3049–3058 [CrossRef]
    [Google Scholar]
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