1887

Abstract

(HCV) in cell culture has a density comparable to that of other members of the family , whereas infectious particles are found partially in low-density fractions, associated with triacylglycerol (TG)-rich lipoproteins (TRLs). In the blood of infected patients, HCV circulates as heterogeneous particles, among which are lipo-viroparticles (LVPs), globular particles rich in TG and containing viral capsid and RNA. The dual viral and lipoprotein nature of LVPs was addressed further with respect to apolipoprotein composition and post-prandial dynamic lipid changes. The TRLs exchangeable apoE, -CII and -CIII, but not the high-density lipoprotein apoA-II, were present on LVPs, as well as the viral envelope proteins. apoB100 and-B48, the two isoforms of the non-exchangeable apoB, were represented equally on LVPs, despite the fact that apoB48 was barely detectable in the plasma of these fasting patients. This indicates that a significant fraction of plasma HCV was associated with apoB48-containing LVPs. Furthermore, LVPs were enriched dramatically and rapidly in triglycerides after a fat meal. As apoB48 is synthesized exclusively by the intestine, these data highlight the preferential association of HCV with chylomicrons, the intestine-derived TRLs. These data raise the question of the contribution of the intestine to the viral load and suggest that the virus could take advantage of TRL assembly and secretion for its own production and of TRL fate to be delivered to the liver.

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2006-10-01
2019-10-19
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References

  1. Agnello, V., Ábel, G., Elfahal, M., Knight, G. B. & Zhang, Q.-X. ( 1999; ). Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci U S A 96, 12766–12771.[CrossRef]
    [Google Scholar]
  2. André, P., Komurian-Pradel, F., Deforges, S. & 7 other authors ( 2002; ). Characterization of low- and very-low-density hepatitis C virus RNA-containing particles. J Virol 76, 6919–6928.[CrossRef]
    [Google Scholar]
  3. Besnard, N. C. & Andre, P. M. ( 1994; ). Automated quantitative determination of hepatitis C virus viremia by reverse transcription-PCR. J Clin Microbiol 32, 1887–1893.
    [Google Scholar]
  4. Bradley, D., McCaustland, K., Krawczynski, K., Spelbring, J., Humphrey, C. & Cook, E. H. ( 1991; ). Hepatitis C virus: buoyant density of the factor VIII-derived isolate in sucrose. J Med Virol 34, 206–208.[CrossRef]
    [Google Scholar]
  5. Carrick, R. J., Schlauder, G. G., Peterson, D. A. & Mushahwar, I. K. ( 1992; ). Examination of the buoyant density of hepatitis C virus by the polymerase chain reaction. J Virol Methods 39, 279–289.[CrossRef]
    [Google Scholar]
  6. Charloteaux, B., Lins, L., Moereels, H. & Brasseur, R. ( 2002; ). Analysis of the C-terminal membrane anchor domains of hepatitis C virus glycoproteins E1 and E2: toward a topological model. J Virol 76, 1944–1958.[CrossRef]
    [Google Scholar]
  7. Deforges, S., Evlashev, A., Perret, M. & 8 other authors ( 2004; ). Expression of hepatitis C virus proteins in epithelial intestinal cells in vivo. J Gen Virol 85, 2515–2523.[CrossRef]
    [Google Scholar]
  8. Field, F. J. & Mathur, S. N. ( 1995; ). Intestinal lipoprotein synthesis and secretion. Prog Lipid Res 34, 185–198.[CrossRef]
    [Google Scholar]
  9. Fisher, E. A. & Ginsberg, H. N. ( 2002; ). Complexity in the secretory pathway: the assembly and secretion of apolipoprotein B-containing lipoproteins. J Biol Chem 277, 17377–17380.[CrossRef]
    [Google Scholar]
  10. Hijikata, M., Shimizu, Y. K., Kato, H., Iwamoto, A., Shih, J. W., Alter, H. J., Purcell, R. H. & Yoshikura, H. ( 1993; ). Equilibrium centrifugation studies of hepatitis C virus: evidence for circulating immune complexes. J Virol 67, 1953–1958.
    [Google Scholar]
  11. Hope, R. G. & McLauchlan, J. ( 2000; ). Sequence motifs required for lipid droplet association and protein stability are unique to the hepatitis C virus core protein. J Gen Virol 81, 1913–1925.
    [Google Scholar]
  12. Jacobs, J. M., Diamond, D. L., Chan, E. Y. & 8 other authors ( 2005; ). Proteome analysis of liver cells expressing a full-length hepatitis C virus (HCV) replicon and biopsy specimens of posttransplantation liver from HCV-infected patients. J Virol 79, 7558–7569.[CrossRef]
    [Google Scholar]
  13. Kaito, M., Watanabe, S., Tsukiyama-Kohara, K. & 7 other authors ( 1994; ). Hepatitis C virus particle detected by immunoelectron microscopic study. J Gen Virol 75, 1755–1760.[CrossRef]
    [Google Scholar]
  14. Kanto, T., Hayashi, N., Takehara, T., Hagiwara, H., Mita, E., Naito, M., Kasahara, A., Fusamoto, H. & Kamada, T. ( 1994; ). Buoyant density of hepatitis C virus recovered from infected hosts: two different features in sucrose equilibrium density-gradient centrifugation related to degree of liver inflammation. Hepatology 19, 296–302.[CrossRef]
    [Google Scholar]
  15. Komurian-Pradel, F., Paranhos-Baccalà, G., Sodoyer, M., Chevallier, P., Mandrand, B., Lotteau, V. & André, P. ( 2001; ). Quantitation of HCV RNA using real-time PCR and fluorimetry. J Virol Methods 95, 111–119.[CrossRef]
    [Google Scholar]
  16. Lindenbach, B. D., Evans, M. J., Syder, A. J. & 8 other authors ( 2005; ). Complete replication of hepatitis C virus in cell culture. Science 309, 623–626.[CrossRef]
    [Google Scholar]
  17. Lindenbach, B. D., Meuleman, P., Ploss, A. & 8 other authors ( 2006; ). Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc Natl Acad Sci U S A 103, 3805–3809.[CrossRef]
    [Google Scholar]
  18. Mahley, R. W. & Rall, S. C., Jr ( 2000; ). Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1, 507–537.[CrossRef]
    [Google Scholar]
  19. McLauchlan, J., Lemberg, M. K., Hope, G. & Martoglio, B. ( 2002; ). Intramembrane proteolysis promotes trafficking of hepatitis C virus core protein to lipid droplets. EMBO J 21, 3980–3988.[CrossRef]
    [Google Scholar]
  20. Miyamoto, H., Okamoto, H., Sato, K., Tanaka, T. & Mishiro, S. ( 1992; ). Extraordinarily low density of hepatitis C virus estimated by sucrose density gradient centrifugation and the polymerase chain reaction. J Gen Virol 73, 715–718.[CrossRef]
    [Google Scholar]
  21. Nielsen, S. U., Bassendine, M. F., Burt, A. D., Bevitt, D. J. & Toms, G. L. ( 2004; ). Characterization of the genome and structural proteins of hepatitis C virus resolved from infected human liver. J Gen Virol 85, 1497–1507.[CrossRef]
    [Google Scholar]
  22. Nielsen, S. U., Bassendine, M. F., Burt, A. D., Martin, C., Pumeechockchai, W. & Toms, G. L. ( 2006; ). Association between hepatitis C virus and very-low-density lipoprotein (VLDL)/LDL analyzed in iodixanol density gradients. J Virol 80, 2418–2428.[CrossRef]
    [Google Scholar]
  23. Patterson, A. P., Chen, Z., Rubin, D. C., Moucadel, V., Iovanna, J. L., Brewer, H. B., Jr & Eggerman, T. L. ( 2003; ). Developmental regulation of apolipoprotein B mRNA editing is an autonomous function of small intestine involving homeobox gene Cdx1. J Biol Chem 278, 7600–7606.[CrossRef]
    [Google Scholar]
  24. Petit, M.-A., Lièvre, M., Peyrol, S., De Sequeira, S., Berthillon, P., Ruigrok, R. W. H. & Trépo, C. ( 2005; ). Enveloped particles in the serum of chronic hepatitis C patients. Virology 336, 144–153.[CrossRef]
    [Google Scholar]
  25. Price, D. A., Bassendine, M. F., Norris, S. M., Golding, C., Toms, G. L., Schmid, M. L., Morris, C. M., Burt, A. D. & Donaldson, P. T. ( 2006; ). Apolipoprotein ε3 allele is associated with persistent hepatitis C virus infection. Gut 55, 715–718.[CrossRef]
    [Google Scholar]
  26. Prince, A. M., Huima-Byron, T., Parker, T. S. & Levine, D. M. ( 1996; ). Visualization of hepatitis C virions and putative defective interfering particles isolated from low-density lipoproteins. J Viral Hepat 3, 11–17.[CrossRef]
    [Google Scholar]
  27. Pringle, C. R. ( 1999; ). Virus taxonomy – 1999. The universal system of virus taxonomy, updated to include the new proposals ratified by the International Committee on Taxonomy of Viruses during 1998. Arch Virol 144, 421–429.[CrossRef]
    [Google Scholar]
  28. Sato, K., Tanaka, T., Okamoto, H., Miyakawa, Y. & Mayumi, M. ( 1996; ). Association of circulating hepatitis G virus with lipoproteins for a lack of binding with antibodies. Biochem Biophys Res Commun 229, 719–725.[CrossRef]
    [Google Scholar]
  29. Smith, M. W., Yue, Z. N., Korth, M. J., Do, H. A., Boix, L., Fausto, N., Bruix, J., Carithers, R. L., Jr & Katze, M. G. ( 2003; ). Hepatitis C virus and liver disease: global transcriptional profiling and identification of potential markers. Hepatology 38, 1458–1467.[CrossRef]
    [Google Scholar]
  30. Su, A. I., Pezacki, J. P., Wodicka, L. & 8 other authors ( 2002; ). Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci U S A 99, 15669–15674.[CrossRef]
    [Google Scholar]
  31. Takahashi, K., Kishimoto, S., Yoshizawa, H., Okamoto, H., Yoshikawa, A. & Mishiro, S. ( 1992; ). p26 protein and 33-nm particle associated with nucleocapsid of hepatitis C virus recovered from the circulation of infected hosts. Virology 191, 431–434.[CrossRef]
    [Google Scholar]
  32. Thomssen, R., Bonk, S., Propfe, C., Heermann, K. H., Kochel, H. G. & Uy, A. ( 1992; ). Association of hepatitis C virus in human sera with beta-lipoprotein. Med Microbiol Immunol (Berl) 181, 293–300.[CrossRef]
    [Google Scholar]
  33. Thomssen, R., Bonk, S. & Thiele, A. ( 1993; ). Density heterogeneities of hepatitis C virus in human sera due to the binding of beta-lipoproteins and immunoglobulins. Med Microbiol Immunol (Berl) 182, 329–334.
    [Google Scholar]
  34. Wakita, T., Pietschmann, T., Kato, T. & 9 other authors ( 2005; ). Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat Med 11, 791–796.[CrossRef]
    [Google Scholar]
  35. Zhong, J., Gastaminza, P., Cheng, G. & 7 other authors ( 2005; ). Robust hepatitis C virus infection in vitro. Proc Natl Acad Sci U S A 102, 9294–9299.[CrossRef]
    [Google Scholar]
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