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Cellular Determinants of Hepatitis C Virus Assembly, Maturation, Degradation, and Secretion
Open accessAbstract
Intracellular infectious hepatitis C virus (HCV) particles display a distinctly higher buoyant density than do secreted virus particles, suggesting that the characteristic low density of extracellular HCV particles is acquired during viral egress. We took advantage of this difference to examine the determinants of assembly, maturation, degradation, and egress of infectious HCV particles. The results demonstrate that HCV assembly and maturation occur in the endoplasmic reticulum (ER) and post-ER compartments, respectively, and that both depend on microsomal transfer protein and apolipoprotein B, in a manner that parallels the formation of very-low-density lipoproteins (VLDL). In addition, they illustrate that only low-density particles are efficiently secreted and that immature particles are actively degraded, in a proteasome-independent manner, in a post-ER compartment of the cell. These results suggest that by coopting the VLDL assembly, maturation, degradation, and secretory machinery of the cell, HCV acquires its hepatocyte tropism and, by mimicry, its tendency to persist.
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Cites
RNAi-mediated gene silencing in non-human primates
Zimmermann, T. S., Lee, A. C. H., Akinc, A., Bramlage, B., Bumcrot, D., Fedoruk, M. N., Harborth, J., Heyes, J. A., Jeffs, L. B., John, M., et al. (2006) · Nature · doi:10.1038/nature04688 · Cited by 1,357
Cited by
The HCV Life Cycle: In vitro Tissue Culture Systems and Therapeutic Targets
Gerold, G., & Pietschmann, T. (2014) · Digestive Diseases · doi:10.1159/000360830 · Cited by 4,854
Understanding the hepatitis C virus life cycle paves the way for highly effective therapies
Scheel, T. K. H., & Rice, C. M. (2013) · Nature Medicine · doi:10.1038/nm.3248 · Cited by 554
Abnormalities of lipid metabolism in hepatitis C virus infection
Negro, F. (2010) · Gut · doi:10.1136/gut.2009.192732 · Cited by 162
Metabolic dysfunction and cancer in HCV: Shared pathways and mutual interactions
Leslie, J., Geh, D., Elsharkawy, A. M., Mann, D. A., & Vacca, M. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.01.029 · Cited by 61
Metadata
- Authors
- Gastaminza, P., Cheng, G., Wieland, S., Zhong, J., Liao, W., & Chisari, F. V.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2008-03
- Volume
- 82
- Issue
- 5
- Pages
- 2120-2129
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- OpenAlex
- W2127274349
- Cited by
- 463
- References
- 1
- FWCI
- 21.07
- Type
- journal article
- Language
- en
- Open access
- green
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- Gastaminza, P., Cheng, G., Wieland, S., Zhong, J., Liao, W., & Chisari, F. V. (2008). Cellular Determinants of Hepatitis C Virus Assembly, Maturation, Degradation, and Secretion. Journal of Virology. https://doi.org/10.1128/jvi.02053-07
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
