Cellular Determinants of Hepatitis C Virus Assembly, Maturation, Degradation, and Secretion
TLDR
The 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.Abstract:
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.read more
Citations
More filters
Journal ArticleDOI
Replication of hepatitis C virus
TL;DR: The development of complete cell-culture systems should now enable the systematic dissection of the entire viral lifecycle, providing insights into the hitherto difficult-to-study early and late steps.
Journal ArticleDOI
Understanding the hepatitis C virus life cycle paves the way for highly effective therapies
TL;DR: Ongoing and future trials will determine the best antiviral combinations and whether the current seemingly rich pipeline is sufficient for successful treatment of all patients in the face of major challenges, such as HCV diversity, viral resistance, the influence of host genetics, advanced liver disease and other co-morbidities.
Journal ArticleDOI
Identification of the Niemann-Pick C1–like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor
Bruno Sainz,Naina Barretto,Danyelle N. Martin,Nobuhiko Hiraga,Michio Imamura,Snawar Hussain,Katherine A. Marsh,Xuemei Yu,Kazuaki Chayama,Waddah A. Alrefai,Susan L. Uprichard +10 more
TL;DR: It is shown that the cellular Niemann-Pick C1–like 1 (NPC1L1) cholesterol uptake receptor is an HCV entry factor amendable to therapeutic intervention and discovered a new antiviral target and potential therapeutic agent.
Journal ArticleDOI
The autophagy machinery is required to initiate hepatitis C virus replication
TL;DR: Autophagy proteins are proviral factors required for translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but they are not required once infection is established, suggesting that different host factors regulate thetranslation of incoming viral genome and translation of progeny HCV RNA once replication is established.
Journal ArticleDOI
A Functional Genomic Screen Identifies Cellular Cofactors of Hepatitis C Virus Replication
Andrew W. Tai,Yair Benita,Lee F. Peng,Sun Suk Kim,Naoya Sakamoto,Ramnik J. Xavier,Raymond T. Chung +6 more
TL;DR: Using a genome-wide siRNA library, 96 human genes that support HCV replication were identified, with a significant number of them being involved in vesicle organization and biogenesis andPhosphatidylinositol 4-kinase PI4KA and multiple subunits of the COPI vesicles coat complex were among the genes identified.
References
More filters
Journal ArticleDOI
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
TL;DR: A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described, providing a pure preparation of undegraded RNA in high yield and can be completed within 4 h.
Journal ArticleDOI
Replication of Subgenomic Hepatitis C Virus RNAs in a Hepatoma Cell Line
TL;DR: This work defines the structure of HCV replicons functional in cell culture and provides the basis for a long-sought cellular system that should allow detailed molecular studies ofHCV and the development of antiviral drugs.
Flaviviridae :T he Viruses and Their Replication
TL;DR: The present research attacked the Flavivirus infection through two mechanisms: Membrane Reorganization and the Compartmentalization and Assembly and Release of Particles from Flaviv virus-infected Cells and Host Resistance to Flaviviral Infection.
Journal ArticleDOI
Robust hepatitis C virus infection in vitro
Jin Zhong,Pablo Gastaminza,Guofeng Cheng,Sharookh B. Kapadia,Takanobu Kato,Dennis R. Burton,Stefan Wieland,Susan L. Uprichard,Takaji Wakita,Francis V. Chisari +9 more
TL;DR: A simple yet robust HCV cell culture infection system based on the HCV JFH-1 molecular clone and Huh-7-derived cell lines that allows the production of virus that can be efficiently propagated in tissue culture is reported.
Journal ArticleDOI
Efficient initiation of HCV RNA replication in cell culture.
TL;DR: This work establishes a robust, cell-based system for genetic and functional analyses of HCV replication and identifies multiple independent adaptive mutations that cluster in the HCV nonstructural protein NS5A and confer increased replicative ability in vitro.
Related Papers (5)
Complete Replication of Hepatitis C Virus in Cell Culture
Brett D. Lindenbach,Brett D. Lindenbach,Brett D. Lindenbach,Matthew J. Evans,Matthew J. Evans,Matthew J. Evans,Andrew J. Syder,Andrew J. Syder,Andrew J. Syder,Benno Wölk,Benno Wölk,Benno Wölk,Timothy L. Tellinghuisen,Timothy L. Tellinghuisen,Timothy L. Tellinghuisen,Christopher C. Liu,Christopher C. Liu,Christopher C. Liu,Toshiaki Maruyama,Toshiaki Maruyama,Toshiaki Maruyama,Richard O. Hynes,Richard O. Hynes,Richard O. Hynes,Dennis R. Burton,Dennis R. Burton,Dennis R. Burton,Jane A. McKeating,Jane A. McKeating,Jane A. McKeating,Charles M. Rice,Charles M. Rice,Charles M. Rice +32 more