Chaperones in hepatitis C virus infection

Khachatoorian, Ronik; French, Samuel W.

doi:10.4254/wjh.v8.i1.9

Cited by 21 publications

(17 citation statements)

References 326 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FKBP52 knockdown decreases NS1 secretion while viral release was not affected. HSP90 has been associated with viral replication of chikungunya virus, Arteriviridae viruses, and hepatitis C virus and has a minor effect on DENV replication (37)(38)(39)(40). However, our results indicate that HSP90 is not associated with NS1 secretion (Fig.…”

Section: Discussionmentioning

confidence: 62%

The Dengue Virus Nonstructural Protein 1 (NS1) Is Secreted from Mosquito Cells in Association with the Intracellular Cholesterol Transporter Chaperone Caveolin Complex

Rosales

Ludert

2019

J Virol

View full text Add to dashboard Cite

Dengue virus (DENV) is a mosquito-borne virus of the family Flaviviridae. The RNA viral genome encodes three structural and seven nonstructural proteins. Nonstructural protein 1 (NS1) is a multifunctional protein actively secreted in vertebrate and mosquito cells during infection. In mosquito cells, NS1 is secreted in a caveolin-1-dependent manner by an unconventional route. The caveolin chaperone complex (CCC) is a cytoplasmic complex formed by caveolin-1 and the chaperones FKBP52, Cy40, and CyA and is responsible for the cholesterol traffic inside the cell. In this work, we demonstrate that in mosquito cells, but not in vertebrate cells, NS1 associates with and relies on the CCC for secretion. Treatment of mosquito cells with classic secretion inhibitors, such as brefeldin A, Golgicide A, and Fli-06, showed no effect on NS1 secretion but significant reductions in recombinant luciferase secretion and virion release. Silencing the expression of CAV-1 or FKBP52 with short interfering RNAs or the inhibition of CyA by cyclosporine resulted in significant decrease in NS1 secretion, again without affecting virion release. Colocalization, coimmunoprecipitation, and proximity ligation assays indicated that NS1 colocalizes and interacts with all proteins of the CCC. In addition, CAV-1 and FKBP52 expression was found augmented in DENV-infected cells. Results obtained with Zika virus-infected cells suggest that in mosquito cells, ZIKV NS1 follows the same secretory pathway as that observed for DENV NS1. These results uncover important differences in the dengue virus-cell interactions between the vertebrate host and the mosquito vector as well as novel functions for the chaperone caveolin complex. IMPORTANCE The dengue virus protein NS1 is secreted efficiently from both infected vertebrate and mosquito cells. Previously, our group reported that NS1 secretion in mosquito cells follows an unconventional secretion pathway dependent on caveolin-1. In this work, we demonstrate that in mosquito cells, but not in vertebrate cells, NS1 secretion takes place in association with the chaperone caveolin complex, a complex formed by caveolin-1 and the chaperones FKBP52, CyA, and Cy40, which are in charge of cholesterol transport inside the cell. Results obtained with ZIKV-infected mosquito cells suggest that ZIKV NS1 is released following an unconventional secretory route in association with the chaperone caveolin complex. These results uncover important differences in the virus-cell interactions between the vertebrate host and the mosquito vector, as well as novel functions for the chaperone caveolin complex. Moreover, manipulation of the NS1 secretory route may prove a valuable strategy to combat these two mosquito-borne diseases. Volume 93 Issue 4 e01985-18 jvi.asm.org 2 on March 18, 2020 by guest http://jvi.asm.org/ Downloaded from plasma membrane, mediated by the CCC, to reach the extracellular space. In addition, data are presented suggesting that a similar pathway is used for the secretion of Zika virus NS1 protein in infected m...

show abstract

Section: Discussionmentioning

confidence: 62%

The Dengue Virus Nonstructural Protein 1 (NS1) Is Secreted from Mosquito Cells in Association with the Intracellular Cholesterol Transporter Chaperone Caveolin Complex

Rosales

Ludert

2019

J Virol

View full text Add to dashboard Cite

show abstract

“…[28] Hsp90 contributes to the maturation,f olding, and stability of severalp roteins required for HCV replication. [28] Hsp90 contributes to the maturation,f olding, and stability of severalp roteins required for HCV replication.…”

Section: Evaluation Of Mode Of Actionmentioning

confidence: 99%

“…The propagation of HCV in hepatocytes involves interaction with cellular chaperones through numerousp athways. [28] Hsp90 contributes to the maturation,f olding, and stability of severalp roteins required for HCV replication. [29] As shown in previouss tudies, targeting Hsp90 efficiently inhibitsH CV replication.…”

Section: Evaluation Of Mode Of Actionmentioning

confidence: 99%

Inhibition of Hepatitis C Replication by Targeting the Molecular Chaperone Hsp90: Synthesis and Biological Evaluation of 4,5,6,7‐Tetrahydrobenzo[1,2‐d]thiazole Derivatives

et al. 2019

View full text Add to dashboard Cite

Cellular chaperones that belong to the heat‐shock protein 90 (Hsp90) family are a prerequisite for successful viral propagation for most viruses. The hepatitis C virus (HCV) uses Hsp90 for maturation, folding, and modification of viral proteins. Based on our previous discovery that marine alkaloid analogues with a 4,5,6,7‐tetrahydrobenzo[1,2‐d]thiazole‐2‐amine structure show inhibition of HCV replication and binding to Hsp90, a series of twelve novel compounds based on this scaffold was designed and synthesized. The aim was improved Hsp90 affinity and anti‐HCV activity. Through structural optimization, improved binding to Hsp90 and specific HCV inhibition in genotype 1b and 2a replicon models was achieved for three compounds belonging to the newly synthesized series. Furthermore, these compounds efficiently inhibited replication of full‐length HCV genotype 2a in a reporter virus RNA assay with IC50 values ranging from 0.03 to 0.6 μm.

show abstract

“…Hepatitis C virus (HCV) is an enveloped positive‐strand RNA virus that belongs to the Hepacivirus genus of the Flaviviridae family; it is approximately 9600 nucleotides in length . Patients are most often infected through blood from an infected individual.…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, untreated HCV infection can lead to liver fibrosis, cirrhosis, portal hypertension, and even hepatocellular carcinoma over time . Each year, half a million deaths occur throughout the world due to HCV‐induced cirrhosis and hepatocellular carcinoma …”

Section: Introductionmentioning

confidence: 99%

Detection of HCV genotypes 1b and 2a by a reverse transcription loop‐mediated isothermal amplification assay

Zhao

Liu

Sun

2017

Journal of Medical Virology

View full text Add to dashboard Cite

Hepatitis C virus (HCV) genotypes 1b and 2a are the major cause of liver disease in northern China; however, conventional detection tools are labor-consuming, technically demanding, and costly. Here, we assessed the specificity, sensitivity, and clinical utility of reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detection of HCV genotypes 1b and 2a. Firstly, clinical samples were collected from HCV genotype 1b and 2a infected patients and the RNA were extracted. Secondly, specificity of RT-LAMP assay for detection HCV genotypes 1b and 2a were tested against viral genomes of other hepatitis viruses. Sensitivity of RT-LAMP assay was determined using serial dilutions of standard HCV genotypes 1b and 2a. The amplified products were detected by both electrophoresis and calcein/Mn -dependent visual methods. Finally, we compared the clinical detection rate of RT-LAMP to that of real-time PCR. RT-LAMP assay showed high specificity to detect HCV genotypes 1b and 2b since there was no cross-reactivity with other hepatitis viruses. Sensitivity of RT-LAMP was 100 IU/mL for both genotypes detected by either electrophoresis or calcein/Mn -dependent visual methods. The detection rate of RT-LAMP assay in clinical samples was also comparable to that of real-time PCR without significant difference between the both assays. This study proposes a newly developed RT-LAMP assay for detection of HCV genotypes 1b and 2a. RT-LAMP is highly specific, sensitive, and simple diagnostic tool which would be useful for screening and early diagnosis of HCV especially in resource-limited environments.

show abstract

Chaperones in hepatitis C virus infection

Cited by 21 publications

References 326 publications

The Dengue Virus Nonstructural Protein 1 (NS1) Is Secreted from Mosquito Cells in Association with the Intracellular Cholesterol Transporter Chaperone Caveolin Complex

The Dengue Virus Nonstructural Protein 1 (NS1) Is Secreted from Mosquito Cells in Association with the Intracellular Cholesterol Transporter Chaperone Caveolin Complex

Inhibition of Hepatitis C Replication by Targeting the Molecular Chaperone Hsp90: Synthesis and Biological Evaluation of 4,5,6,7‐Tetrahydrobenzo[1,2‐d]thiazole Derivatives

Detection of HCV genotypes 1b and 2a by a reverse transcription loop‐mediated isothermal amplification assay

Contact Info

Product

Resources

About