Different mechanisms of hepatitis C virus RNA polymerase activation by cyclophilin A and B in vitro

Weng, Leiyun; Tian, Xiao; Gao, Yayi; Watashi, Koichi; Shimotohno, Kunitada; Wakita, Takaji; Kohara, Michinori; Toyoda, Tetsuya

doi:10.1016/j.bbagen.2012.08.017

Cited by 8 publications

(6 citation statements)

References 66 publications

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“…However, CypA was the protein that exhibited the most significant p value (0.000000019). CypA has been found to participate in the replication of several viruses. − …”

Section: Results and Discussionmentioning

confidence: 99%

Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication

et al. 2017

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Yellow fever virus (YFV) replication is highly dependent on host cell factors. YFV NS4B is reported to be involved in viral replication and immune evasion. Here interactions between NS4B and human proteins were determined using a GST pull-down assay and analyzed using 1-DE and LC-MS/MS. We present a total of 207 proteins confirmed using Scaffold 3 Software. Cyclophilin A (CypA), a protein that has been shown to be necessary for the positive regulation of flavivirus replication, was identified as a possible NS4B partner. 59 proteins were found to be significantly increased when compared with a negative control, and CypA exhibited the greatest difference, with a 22-fold change. Fisher's exact test was significant for 58 proteins, and the p value of CypA was the most significant (0.000000019). The Ingenuity Systems software identified 16 pathways, and this analysis indicated sirolimus, an mTOR pathway inhibitor, as a potential inhibitor of CypA. Immunofluorescence and viral plaque assays showed a significant reduction in YFV replication using sirolimus and cyclosporine A (CsA) as inhibitors. Furthermore, YFV replication was strongly inhibited in cells treated with both inhibitors using reporter BHK-21-rep-YFV17D-LucNeoIres cells. Taken together, these data suggest that CypA-NS4B interaction regulates YFV replication. Finally, we present the first evidence that YFV inhibition may depend on NS4B-CypA interaction.

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“…However, CypA was the protein that exhibited the most significant p value (0.000000019). CypA has been found to participate in the replication of several viruses. − …”

Section: Results and Discussionmentioning

confidence: 99%

Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication

et al. 2017

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“…23,28,56,57 In particular, CypB induced integrin-mediated cell adhesion by its interaction with CD147, CD98, integrins, 58 which was dependent on protein kinase (PK) C-delta activation and was critical for ERK1/2-mediated signalling. CypB has been associated with osteogenesis imperfecta, 49,59 cancer, 55,60,61 CMV infection, 62,63 HIV, 64 neurodegeneration, 65 asthma, 34 and ageing. 66 A study by Kainer and Doris 67 suggested the importance of CypB in hypertension as they showed increased CypB levels in the renal proximal tubules of spontaneous hypertensive rats (SHR).…”

Section: Cyclophilin Bmentioning

confidence: 99%

Peptidyl-prolyl isomerases: a full cast of critical actors in cardiovascular diseases

Perrucci

Gowran

Zanobini

et al. 2015

Cardiovascular Research

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Peptidyl-prolyl cis-trans-isomerases are a highly conserved family of immunophilins. The three peptidyl-prolyl cis-trans-isomerase subfamilies are cyclophilins, FK-506-binding proteins, and parvulins. Peptidyl-prolyl cis-trans-isomerases are expressed in multiple human tissues and regulate different cellular functions, e.g. calcium handling, protein folding, and gene expression. Moreover, these subfamilies have been shown to be consistently involved in several cardiac and vascular diseases including heart failure, arrhythmias, vascular stenosis, endothelial dysfunction, atherosclerosis, and hypertension. This review provides a concise description of the peptidyl-prolyl cis-trans-isomerases and presents an incisive selection of studies focused on their relationship with cardiovascular diseases.

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“…Interestingly, one study reported the selection of NS5B mutants that were resistant to CsA; these mutations in NS5B conferred an increased ability for NS5B to bind RNA in the presence of CsA. Complementary studies supported these observations by showing that CypB increases RNA synthesis through binding to NS5B [ 67 ], although in vitro enzyme assays suggested that CypB may activate NS5B in a genotype-specific manner [ 68 ]. These findings are consistent with a role for Cyps in regulating HCV RNA replication.…”

Section: Cyclophilins and Hcv Infectionmentioning

confidence: 99%

Cyclophilins and Their Roles in Hepatitis C Virus and Flavivirus Infections: Perspectives for Novel Antiviral Approaches

Gallardo-Flores

Colpitts

2021

Pathogens

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Cyclophilins are cellular peptidyl-prolyl isomerases that play an important role in viral infections, with demonstrated roles in the replication of hepatitis C virus (HCV) and other viruses in the Flaviviridae family, such as dengue virus (DENV) and yellow fever virus (YFV). Here, we discuss the roles of cyclophilins in HCV infection and provide a comprehensive overview of the mechanisms underlying the requirement for cyclophilins during HCV replication. Notably, cyclophilin inhibitor therapy has been demonstrated to be effective in reducing HCV replication in chronically infected patients. While the roles of cyclophilins are relatively well-understood for HCV infection, cyclophilins are more recently emerging as host factors for flavivirus infection as well, providing potential new therapeutic avenues for these viral infections which currently lack antiviral therapies. However, further studies are required to elucidate the roles of cyclophilins in flavivirus replication. Here, we review the current knowledge of the role of cyclophilins in HCV infection to provide a conceptual framework to understand how cyclophilins may contribute to other viral infections, such as DENV and YFV. Improved understanding of the roles of cyclophilins in viral infection may open perspectives for the development of cyclophilin inhibitors as effective antiviral therapeutics for HCV and related viruses.

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Different mechanisms of hepatitis C virus RNA polymerase activation by cyclophilin A and B in vitro

Cited by 8 publications

References 66 publications

Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication

Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication

Peptidyl-prolyl isomerases: a full cast of critical actors in cardiovascular diseases

Cyclophilins and Their Roles in Hepatitis C Virus and Flavivirus Infections: Perspectives for Novel Antiviral Approaches

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