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Volume 90, Issue 5

A role for autophagolysosomes in dengue virus 3 production in HepG2 cells Free

Abstract

We have recently proposed that amphisomes act as a site for translation and replication of dengue virus (DENV)-2 and that DENV-2 entry and replication are linked through an ongoing association with membranes of an endosomal–autophagosomal lineage. In this report, we present the results of an investigation into the interaction between DENV-3 and the autophagy machinery. Critically, treatment with the lysosomal fusion inhibitor -asparagine differentiated the interaction of DENV-3 from that of DENV-2. Inhibition of fusion of autophagosomes and amphisomes with lysosomes resulted in decreased DENV-3 production, implying a role for the autophagolysosome in the DENV-3 life cycle. Evidence based upon the co-localization of LC3 and cathepsin D with double stranded RNA and NS1 protein, as assessed by confocal microscopy, support a model in which DENV-3 interacts with both amphisomes and autophagolysosomes. These results demonstrate that the interactions between DENV and the host cell autophagy machinery are complex and may be determined in part by virus-encoded factors.

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2009-05-01
2024-04-23
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References

  1. Acosta E. G., Castilla V., Damonte E. B. 2008; Functional entry of dengue virus into Aedes albopictus mosquito cells is dependent on clathrin-mediated endocytosis. J Gen Virol 89:474–484 [CrossRef]
     [Google Scholar]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. Eskelinen E. L. 2005; Maturation of autophagic vacuoles in mammalian cells. Autophagy 1:1–10 [CrossRef]
     [Google Scholar]
  7. Eskelinen E. L., Illert A. L., Tanaka Y., Schwarzmann G., Blanz J., Von Figura K., Saftig P. 2002; Role of LAMP-2 in lysosome biogenesis and autophagy. Mol Biol Cell 13:3355–3368 [CrossRef]
     [Google Scholar]
  8. Espert L., Codogno P., Biard-Piechaczyk M. 2007; Involvement of autophagy in viral infections: antiviral function and subversion by viruses. J Mol Med 85:811–823 [CrossRef]
     [Google Scholar]
  9. Gordon P. B., Seglen P. O. 1988; Prelysosomal convergence of autophagic and endocytic pathways. Biochem Biophys Res Commun 151:40–47 [CrossRef]
     [Google Scholar]
  10. Guzman M. G., Kouri G. 2002; Dengue: an update. Lancet Infect Dis 2:33–42 [CrossRef]
     [Google Scholar]
  11. Halstead S. B. 1988; Pathogenesis of dengue: challenges to molecular biology. Science 239:476–481 [CrossRef]
     [Google Scholar]
  12. Heinz F. X., Stiasny K., Allison S. L. 2004; The entry machinery of flaviviruses. Arch Virol Suppl 18:133–137
     [Google Scholar]
  13. Holmes E. C., Twiddy S. S. 2003; The origin, emergence and evolutionary genetics of dengue virus. Infect Genet Evol 3:19–28 [CrossRef]
     [Google Scholar]
  14. 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]
  15. 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]
  16. 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]
  17. Ko K. K., Igarashi A., Fukai K. 1979; Electron microscopic observations on Aedes albopictus cells infected with dengue viruses. Arch Virol 62:41–52 [CrossRef]
     [Google Scholar]
  18. 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]
  19. Lee H. K., Iwasaki A. 2008; Autophagy and antiviral immunity. Curr Opin Immunol 20:23–29 [CrossRef]
     [Google Scholar]
  20. 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]
  21. 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]
  22. 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]
  23. Malavige G. N., Fernando S., Fernando D. J., Seneviratne S. L. 2004; Dengue viral infections. Postgrad Med J 80:588–601 [CrossRef]
     [Google Scholar]
  24. Meijer A. J., Codogno P. 2006; Signalling and autophagy regulation in health, aging and disease. Mol Aspects Med 27:411–425 [CrossRef]
     [Google Scholar]
  25. Miller S., Krijnse-Locker J. 2008; Modification of intracellular membrane structures for virus replication. Nat Rev Microbiol 6:363–374 [CrossRef]
     [Google Scholar]
  26. Mizushima N., Yoshimori T. 2007; How to interpret LC3 immunoblotting. Autophagy 3:542–545 [CrossRef]
     [Google Scholar]
  27. 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]
  28. 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]
  29. 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]
  30. 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]
  31. 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]
  32. Noda T., Ohsumi Y. 1998; Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 273:3963–3966 [CrossRef]
     [Google Scholar]
  33. Ohsumi Y. 2001; Molecular dissection of autophagy: two ubiquitin-like systems. Nat Rev Mol Cell Biol 2:211–216 [CrossRef]
     [Google Scholar]
  34. Panyasrivanit M., Khakpoor A., Wikan N., Smith D. R. 2009; Co-localization of constituents of the dengue virus translation and replication machinery with amphisomes. J Gen Virol 90:448–456 [CrossRef]
     [Google Scholar]
  35. 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]
  36. Salonen A., Ahola T., Kääriäinen L. 2005; Viral RNA replication in association with cellular membranes. Curr Top Microbiol Immunol 285:139–173
     [Google Scholar]
  37. 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]
  38. Seglen P. O., Berg T. O., Blankson H., Fengsrud M., Holen I., Strømhaug P. E. 1996; Structural aspects of autophagy. Adv Exp Med Biol 389:103–111
     [Google Scholar]
  39. Seneviratne S. L., Malavige G. N., de Silva H. J. 2006; Pathogenesis of liver involvement during dengue viral infections. Trans R Soc Trop Med Hyg 100:608–614 [CrossRef]
     [Google Scholar]
  40. 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]
  41. Suksanpaisan L., Cabrera-Hernandez A., Smith D. R. 2007; Infection of human primary hepatocytes with dengue virus serotype 2. J Med Virol 79:300–307 [CrossRef]
     [Google Scholar]
  42. Taylor P. R., Gordon S., Martinez-Pomares L. 2005; The mannose receptor: linking homeostasis and immunity through sugar recognition. Trends Immunol 26:104–110 [CrossRef]
     [Google Scholar]
  43. 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]
  44. Thepparit C., Phoolcharoen W., Suksanpaisan L., Smith D. R. 2004; Internalization and propagation of the dengue virus in human hepatoma (HepG2) cells. Intervirology 47:78–86 [CrossRef]
     [Google Scholar]
  45. 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]
  46. Xie Z., Klionsky D. J. 2007; Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9:1102–1109 [CrossRef]
     [Google Scholar]
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A role for autophagolysosomes in dengue virus 3 production in HepG2 cells
J. Gen. Virol. 90, 1093 (2009); https://doi.org/10.1099/vir.0.007914-0
/content/journal/jgv/10.1099/vir.0.007914-0
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