1887

Abstract

Japanese encephalitis virus (JEV) is an enveloped flavivirus and the most common agent of viral encephalitis. It enters cells through receptor-mediated endocytosis and low pH-triggered membrane fusion. Although lipid rafts, cholesterol-enriched lipid-ordered membrane domains, have been shown to participate in JEV entry, the mechanisms of the early events of JEV infection, including the cellular receptors of JEV, remain largely unknown. In the current study, it was demonstrated that heat-shock protein 70 (HSP70), rather than other members of the HSP70 family, was required for JEV entry into a human cell line. Cell-surface expression of HSP70 and a direct interaction between JEV envelope (E) protein and HSP70 were observed. Biochemical fractionation showed that HSP70 clearly migrated into the raft fraction after virus infection and co-fractioned with E protein. Depletion of cholesterol shifted the E protein and HSP70 to a non-raft membrane and decreased JEV entry without affecting virus binding to host cells. Notably, recruitment of HSP70 into lipid rafts was required for activation of the phosphoinositide 3-kinase/Akt signalling pathway in the early stage of JEV infection. These results indicate that lipid rafts facilitate JEV entry, possibly by providing a convenient platform to concentrate JEV and its receptors on the host-cell membrane.

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2012-01-01
2019-10-18
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References

  1. Bender F. C. , Whitbeck J. C. , Ponce de Leon M. , Lou H. , Eisenberg R. J. , Cohen G. H. . ( 2003; ). Specific association of glycoprotein B with lipid rafts during herpes simplex virus entry. . J Virol 77:, 9542–9552. [CrossRef] [PubMed]
    [Google Scholar]
  2. Boonsanay V. , Smith D. R. . ( 2007; ). Entry into and production of the Japanese encephalitis virus from C6/36 cells. . Intervirology 50:, 85–92. [CrossRef] [PubMed]
    [Google Scholar]
  3. Brazzoli M. , Bianchi A. , Filippini S. , Weiner A. , Zhu Q. , Pizza M. , Crotta S. . ( 2008; ). CD81 is a central regulator of cellular events required for hepatitis C virus infection of human hepatocytes. . J Virol 82:, 8316–8329.[CrossRef]
    [Google Scholar]
  4. Broquet A. H. , Thomas G. , Masliah J. , Trugnan G. , Bachelet M. . ( 2003; ). Expression of the molecular chaperone Hsp70 in detergent-resistant microdomains correlates with its membrane delivery and release. . J Biol Chem 278:, 21601–21606. [CrossRef] [PubMed]
    [Google Scholar]
  5. Brown G. , Rixon H. W. , Steel J. , McDonald T. P. , Pitt A. R. , Graham S. , Sugrue R. J. . ( 2005; ). Evidence for an association between heat shock protein 70 and the respiratory syncytial virus polymerase complex within lipid-raft membranes during virus infection. . Virology 338:, 69–80. [CrossRef] [PubMed]
    [Google Scholar]
  6. Chazal N. , Gerlier D. . ( 2003; ). Virus entry, assembly, budding, and membrane rafts. . Microbiol Mol Biol Rev 67:, 226–237. [CrossRef] [PubMed]
    [Google Scholar]
  7. Chen S. , Bawa D. , Besshoh S. , Gurd J. W. , Brown I. R. . ( 2005; ). Association of heat shock proteins and neuronal membrane components with lipid rafts from the rat brain. . J Neurosci Res 81:, 522–529. [CrossRef] [PubMed]
    [Google Scholar]
  8. Chung C.-S. , Huang C.-Y. , Chang W. . ( 2005; ). Vaccinia virus penetration requires cholesterol and results in specific viral envelope proteins associated with lipid rafts. . J Virol 79:, 1623–1634. [CrossRef] [PubMed]
    [Google Scholar]
  9. Crill W. D. , Roehrig J. T. . ( 2001; ). Monoclonal antibodies that bind to domain III of dengue virus E glycoprotein are the most efficient blockers of virus adsorption to Vero cells. . J Virol 75:, 7769–7773. [CrossRef] [PubMed]
    [Google Scholar]
  10. Das S. , Laxminarayana S. V. , Chandra N. , Ravi V. , Desai A. . ( 2009; ). Heat shock protein 70 on Neuro2a cells is a putative receptor for Japanese encephalitis virus. . Virology 385:, 47–57. [CrossRef] [PubMed]
    [Google Scholar]
  11. Das S. , Chakraborty S. , Basu A. . ( 2010; ). Critical role of lipid rafts in virus entry and activation of phosphoinositide 3′ kinase/Akt signaling during early stages of Japanese encephalitis virus infection in neural stem/progenitor cells. . J Neurochem 115:, 537–549. [CrossRef] [PubMed]
    [Google Scholar]
  12. Gehrmann M. , Liebisch G. , Schmitz G. , Anderson R. , Steinem C. , De Maio A. , Pockley G. , Multhoff G. . ( 2008; ). Tumor-specific Hsp70 plasma membrane localization is enabled by the glycosphingolipid Gb3. . PLoS One 3:, e1925.[CrossRef]
    [Google Scholar]
  13. Guerrero C. A. , Bouyssounade D. , Zárate S. , Isa P. , López T. , Espinosa R. , Romero P. , Méndez E. , López S. , Arias C. F. . ( 2002; ). Heat shock cognate protein 70 is involved in rotavirus cell entry. . J Virol 76:, 4096–4102. [CrossRef] [PubMed]
    [Google Scholar]
  14. Ikeda M. , Abe K. , Yamada M. , Dansako H. , Naka K. , Kato N. . ( 2006; ). Different anti-HCV profiles of statins and their potential for combination therapy with interferon. . Hepatology 44:, 117–125. [CrossRef] [PubMed]
    [Google Scholar]
  15. Ilangumaran S. , Hoessli D. C. . ( 1998; ). Effects of cholesterol depletion by cyclodextrin on the sphingolipid microdomains of the plasma membrane. . Biochem J 335:, 433–440.[PubMed]
    [Google Scholar]
  16. Kapadia S. B. , Barth H. , Baumert T. , McKeating J. A. , Chisari F. V. . ( 2007; ). Initiation of HCV infection is dependent on cholesterol and cooperativity between CD81 and scavenger receptor B type I. . J Virol 81:, 374–383.[CrossRef]
    [Google Scholar]
  17. Kimura T. , Kimura-Kuroda J. , Nagashima K. , Yasui K. . ( 1994; ). Analysis of virus–cell binding characteristics on the determination of Japanese encephalitis virus susceptibility. . Arch Virol 139:, 239–251. [CrossRef] [PubMed]
    [Google Scholar]
  18. Lee E. , Lobigs M. . ( 2002; ). Mechanism of virulence attenuation of glycosaminoglycan-binding variants of Japanese encephalitis virus and Murray Valley encephalitis virus. . J Virol 76:, 4901–4911. [CrossRef] [PubMed]
    [Google Scholar]
  19. Lee C.-J. , Liao C.-L. , Lin Y.-L. . ( 2005; ). Flavivirus activates phosphatidylinositol 3-kinase signaling to block caspase-dependent apoptotic cell death at the early stage of virus infection. . J Virol 79:, 8388–8399. [CrossRef] [PubMed]
    [Google Scholar]
  20. Lee C.-J. , Lin H.-R. , Liao C.-L. , Lin Y.-L. . ( 2008; ). Cholesterol effectively blocks entry of flavivirus. . J Virol 82:, 6470–6480. [CrossRef] [PubMed]
    [Google Scholar]
  21. Mackenzie J. M. , Khromykh A. A. , Parton R. G. . ( 2007; ). Cholesterol manipulation by West Nile virus perturbs the cellular immune response. . Cell Host Microbe 2:, 229–239. [CrossRef] [PubMed]
    [Google Scholar]
  22. Mandl C. W. , Allison S. L. , Holzmann H. , Meixner T. , Heinz F. X. . ( 2000; ). Attenuation of tick-borne encephalitis virus by structure-based site-specific mutagenesis of a putative flavivirus receptor binding site. . J Virol 74:, 9601–9609. [CrossRef] [PubMed]
    [Google Scholar]
  23. Mañes S. , del Real G. , Martínez-A C. . ( 2003; ). Pathogens: raft hijackers. . Nat Rev Immunol 3:, 557–568. [CrossRef] [PubMed]
    [Google Scholar]
  24. Matsushima-Nishiwaki R. , Adachi S. , Yoshioka T. , Yasuda E. , Yamagishi Y. , Matsuura J. , Muko M. , Iwamura R. , Noda T. . & other authors ( 2011; ). Suppression by heat shock protein 20 of hepatocellular carcinoma cell proliferation via inhibition of the mitogen-activated protein kinases and AKT pathways. . J Cell Biochem 112:, 3430–3439.[CrossRef]
    [Google Scholar]
  25. Mayer M. P. . ( 2005; ). Recruitment of Hsp70 chaperones: a crucial part of viral survival strategies. . Rev Physiol Biochem Pharmacol 153:, 1–46. [CrossRef] [PubMed]
    [Google Scholar]
  26. McMinn P. C. . ( 1997; ). The molecular basis of virulence of the encephalitogenic flaviviruses. . J Gen Virol 78:, 2711–2722.[PubMed]
    [Google Scholar]
  27. Medigeshi G. R. , Hirsch A. J. , Streblow D. N. , Nikolich-Zugich J. , Nelson J. A. . ( 2008; ). West Nile virus entry requires cholesterol-rich membrane microdomains and is independent of αvβ3 integrin. . J Virol 82:, 5212–5219. [CrossRef] [PubMed]
    [Google Scholar]
  28. Misra U. K. , Kalita J. . ( 2010; ). Overview: Japanese encephalitis. . Prog Neurobiol 91:, 108–120. [CrossRef] [PubMed]
    [Google Scholar]
  29. Nadeau S. I. , Landry J. . ( 2007; ). Mechanisms of activation and regulation of the heat shock-sensitive signaling pathways. . Adv Exp Med Biol 594:, 100–113. [CrossRef] [PubMed]
    [Google Scholar]
  30. Popik W. , Alce T. M. , Au W. C. . ( 2002; ). Human immunodeficiency virus type 1 uses lipid raft-colocalized CD4 and chemokine receptors for productive entry into CD4+ T cells. . J Virol 76:, 4709–4722. [CrossRef] [PubMed]
    [Google Scholar]
  31. Rafiee P. , Ogawa H. , Heidemann J. , Li M. S. , Aslam M. , Lamirand T. H. , Fisher P. J. , Graewin S. J. , Dwinell M. B. . & other authors ( 2003; ). Isolation and characterization of human esophageal microvascular endothelial cells: mechanisms of inflammatory activation. . Am J Physiol Gastrointest Liver Physiol 285:, G1277–G1292.[PubMed] [CrossRef]
    [Google Scholar]
  32. Rawat S. S. , Viard M. , Gallo S. A. , Rein A. , Blumenthal R. , Puri A. . ( 2003; ). Modulation of entry of enveloped viruses by cholesterol and sphingolipids. . Mol Membr Biol 20:, 243–254. [CrossRef] [PubMed]
    [Google Scholar]
  33. Ren J. , Ding T. , Zhang W. , Song J. , Ma W. . ( 2007; ). Does Japanese encephalitis virus share the same cellular receptor with other mosquito-borne flaviviruses on the C6/36 mosquito cells. ? Virol J 4:, 83–89. [CrossRef] [PubMed]
    [Google Scholar]
  34. Reyes-Del Valle J. , Chávez-Salinas S. , Medina F. , Del Angel R. M. . ( 2005; ). Heat shock protein 90 and heat shock protein 70 are components of dengue virus receptor complex in human cells. . J Virol 79:, 4557–4567. [CrossRef] [PubMed]
    [Google Scholar]
  35. Rohde M. , Daugaard M. , Jensen M. H. , Helin K. , Nylandsted J. , Jäättelä M. . ( 2005; ). Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms. . Genes Dev 19:, 570–582. [CrossRef] [PubMed]
    [Google Scholar]
  36. Rosa D. , Campagnoli S. , Moretto C. , Guenzi E. , Cousens L. , Chin M. , Dong C. , Weiner A. J. , Lau J. Y. . & other authors ( 1996; ). A quantitative test to estimate neutralizing antibodies to the hepatitis C virus: cytofluorimetric assessment of envelope glycoprotein 2 binding to target cells. . Proc Natl Acad Sci U S A 93:, 1759–1763. [CrossRef] [PubMed]
    [Google Scholar]
  37. Rothwell C. , Lebreton A. , Young Ng C. , Lim J. Y. , Liu W. , Vasudevan S. , Labow M. , Gu F. , Gaither L. A. . ( 2009; ). Cholesterol biosynthesis modulation regulates dengue viral replication. . Virology 389:, 8–19. [CrossRef] [PubMed]
    [Google Scholar]
  38. Sagara Y. , Ishida C. , Inoue Y. , Shiraki H. , Maeda Y. . ( 1998; ). 71-kilodalton heat shock cognate protein acts as a cellular receptor for syncytium formation induced by human T-cell lymphotropic virus type 1. . J Virol 72:, 535–541.[PubMed]
    [Google Scholar]
  39. Stiasny K. , Koessl C. , Heinz F. X. . ( 2003; ). Involvement of lipids in different steps of the flavivirus fusion mechanism. . J Virol 77:, 7856–7862. [CrossRef] [PubMed]
    [Google Scholar]
  40. Su C.-M. , Liao C.-L. , Lee Y.-L. , Lin Y.-L. . ( 2001; ). Highly sulfated forms of heparin sulfate are involved in Japanese encephalitis virus infection. . Virology 286:, 206–215. [CrossRef] [PubMed]
    [Google Scholar]
  41. Tani H. , Komoda Y. , Matsuo E. , Suzuki K. , Hamamoto I. , Yamashita T. , Moriishi K. , Fujiyama K. , Kanto T. . & other authors ( 2007; ). Replication-competent recombinant vesicular stomatitis virus encoding hepatitis C virus envelope proteins. . J Virol 81:, 8601–8612. [CrossRef] [PubMed]
    [Google Scholar]
  42. Tani H. , Shiokawa M. , Kaname Y. , Kambara H. , Mori Y. , Abe T. , Moriishi K. , Matsuura Y. . ( 2010; ). Involvement of ceramide in the propagation of Japanese encephalitis virus. . J Virol 84:, 2798–2807. [CrossRef] [PubMed]
    [Google Scholar]
  43. Triantafilou K. , Fradelizi D. , Wilson K. , Triantafilou M. . ( 2002; ). GRP78, a coreceptor for coxsackievirus A9, interacts with major histocompatibility complex class I molecules which mediate virus internalization. . J Virol 76:, 633–643. [CrossRef] [PubMed]
    [Google Scholar]
  44. Wu S.-C. , Chiang J.-R. , Lin C.-W. . ( 2004; ). Novel cell adhesive glycosaminoglycan-binding proteins of Japanese encephalitis virus. . Biomacromolecules 5:, 2160–2164. [CrossRef] [PubMed]
    [Google Scholar]
  45. Wu Y.-P. , Chang C.-M. , Hung C.-Y. , Tsai M.-C. , Schuyler S. C. , Wang R. Y. . ( 2011; ). Japanese encephalitis virus co-opts the ER-stress response protein GRP78 for viral infectivity. . Virol J 8:, 128–137. [CrossRef] [PubMed]
    [Google Scholar]
  46. Zárate S. , Cuadras M. A. , Espinosa R. , Romero P. , Juárez K. O. , Camacho-Nuez M. , Arias C. F. , López S. . ( 2003; ). Interaction of rotaviruses with Hsc70 during cell entry is mediated by VP5. . J Virol 77:, 7254–7260. [CrossRef] [PubMed]
    [Google Scholar]
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