The heat shock cognate protein 70 is associated with hepatitis C virus particles and modulates virus infectivity†

Parent, Romain; Qu, Xiaoyu; Petit, Marie; Beretta, Laura

doi:10.1002/hep.22852

Cited by 77 publications

(72 citation statements)

References 37 publications

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“…82 In the last few years, several host cell factors required for infectious HCV particle production have been described, including OSBP, Annexin AII and the heat shock cognate protein 70 (Hsc70). 157 The latter has been identified as a component of virus particles produced in cell culture. Surprisingly, Hsc70-specific antibodies can neutralize infectivity arguing that at least a fraction of this protein is accessible on the surface of virus particles.…”

Section: Discussionmentioning

confidence: 99%

“…Surprisingly, Hsc70-specific antibodies can neutralize infectivity arguing that at least a fraction of this protein is accessible on the surface of virus particles. 157 In addition, Hsc70 appears to be required for LDs integrity because their volume was reduced upon silencing of Hsc70 expression. 157 It is well established that apolipoproteins (Apo) play a key role in HCV assembly and release.…”

Section: Discussionmentioning

confidence: 99%

“…157 In addition, Hsc70 appears to be required for LDs integrity because their volume was reduced upon silencing of Hsc70 expression. 157 It is well established that apolipoproteins (Apo) play a key role in HCV assembly and release. RNAi-mediated knockdown of ApoB and ApoE as well as pharmacological inhibition of microsomal triglyceride transfer protein (MTP), an enzyme crucial for ApoB maturation and VLDL secretion, have been proven effective in inhibiting HCV production in Huh7 cells, suggesting that secretion of HCV relies on the VLDL pathway.…”

Section: Discussionmentioning

confidence: 99%

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Hepatitis c virus and host cell lipids: An intimate connection

Alvisi¹,

Madan²,

2011

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Hepatitis c virus and host cell lipids: An intimate connection

Alvisi¹,

Madan²,

2011

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“…HSC70 is a constitutively expressed chaperon protein whereas Hsp72 is a stress-inducible protein and can be induced by various stresses, such as heat shock, UV radiation and osmotic stress. HSC70 has previously been demonstrated to be part of the HCV viral particles and plays roles in the budding and entry processes of the HCV lifecycle, but has no effects on intracellular HCV RNA replication (34). Hsp72 (or Hsp70 -1) is a general name for Hsp70 -1a and Hsp70 -1b which are encoded by two cross-linked genes, HSPA1A and HSPA1B, respectively (35,36).…”

Section: Hsc70 and Hsp72 Are Ns5a-interacting Cellular Proteins-mentioning

confidence: 99%

Heat Shock Protein 72 Is Associated with the Hepatitis C Virus Replicase Complex and Enhances Viral RNA Replication

Chen¹,

Chen²,

Chow

et al. 2010

Journal of Biological Chemistry

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The NS5A protein of the hepatitis C virus (HCV) is an integral component of the viral replicase. It also modulates cellular signaling and perturbs host interferon responses. The multifunctional characteristics of NS5A are mostly attributed to its ability to interact with various cellular proteins. This study aimed to identify the novel cellular factors that interact with NS5A and decipher the significance of this interaction in viral replication. The NS5A-interacting proteins were purified by the tandem affinity purification (TAP) procedure from cells expressing NS5A and identified by mass spectrometry. The chaperone protein Hsp72 was identified herein. In vivo protein-protein interaction was verified by co-immunoprecipitation and an in situ proximity ligation assay. In addition to NS5A, Hsp72 was also associated with other members of the replicase complex, NS3 and NS5B, suggesting that it might be directly involved in the HCV replication complex. Hsp72 plays a positive regulatory role in HCV RNA replication by increasing levels of the replicase complex, which was attributed either to the increased stability of the viral proteins in the replicase complex or to the enhanced translational activity of the internal ribosome entry site of HCV. The fact that the host chaperone protein Hsp72 is involved in HCV RNA replication may represent a therapeutic target for controlling virus production. The hepatitis C virus (HCV),3 a hepacivirus in the Flaviviridae family, is the leading cause of acute and chronic hepatitis worldwide (1, 2). Currently, around 170 million individuals are chronically infected with HCV. HCV infection often leads to liver cirrhosis and hepatocellular carcinoma (1-3).The replication of HCV is entirely cytoplasmic. The HCV lifecycle starts when enveloped virus particles attach to the cell membrane and interact with specific surface receptor(s). After internalization and membrane fusion in an endosome, the HCV genome is released into the cytoplasm. This genome serves not only as the messenger RNA for the translation of viral proteins but also as the template for viral RNA replication. All viral proteins are directly or indirectly associated with the endoplasmic reticulum (ER) membrane, where replication and assembly take place. The HCV non-structural proteins, NS3/NS4A, NS4B, NS5A, and NS5B, and likely several host-derived factors function as a replicase complex, which executes the replication process. Once the newly synthesized nascent RNA is packaged in the particle, the virion forms by budding into the ER and leaves the cell through the secretory pathway (4 -7).Among the HCV viral proteins, NS5A has been demonstrated to be multi-functional, which supports the replication and survival of HCV. The requirement for NS5A in HCV RNA replication has been supported by numerous lines of evidence (8 -17). The other important functions of NS5A lie in its potential to perturb the interferon responses and modulate the signaling pathways of host cells; those are mostly dependent on its interaction with cellular ...

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“…Hsc70 participates in several cellular processes, including viral replication (Watanabe et al 2006;Hayashi et al 2009), viral infection (Parent et al 2009), and autoimmune inflammation (Alam et al 2009). Hsc70 functions as a chaperone by trafficking proteins to different cellular compartments (Pilon and Schekman 1999) and is important in endocytosis (de Waegh and Brady 1989).…”

Section: Introductionmentioning

confidence: 99%

PKCι counteracts oxidative stress by regulating Hsc70 in an esophageal cancer cell line

Wang¹,

Yang²,

Yang³

et al. 2013

Cell Stress and Chaperones

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Using a glutathione S-transferase pull-down liquid chromatography-coupled tandem mass spectrometry approach and immunoprecipitation/immunoblot analysis, we found that heat shock cognate protein 70 (Hsc70) was involved in the complex formed by atypical protein kinase Cι (PKCι) and LC3 in the esophageal cancer cell line KYSE30. Further study indicated that Hsc70 was targeted by autophagic degradation, and knockdown of PKCι downregulated Hsc70 by promoting autophagy. PKCι knockdown sensitized cells to oxidative stress-induced apoptosis, whereas forced PKCι expression counteracted the oxidative stress-induced apoptosis via Hsc70.

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The heat shock cognate protein 70 is associated with hepatitis C virus particles and modulates virus infectivity†

Cited by 77 publications

References 37 publications

Hepatitis c virus and host cell lipids: An intimate connection

Hepatitis c virus and host cell lipids: An intimate connection

Heat Shock Protein 72 Is Associated with the Hepatitis C Virus Replicase Complex and Enhances Viral RNA Replication

PKCι counteracts oxidative stress by regulating Hsc70 in an esophageal cancer cell line

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