Targeting Extracellular Cyclophilin A via an Albumin‐Binding Cyclosporine A Analogue

ChemMedChem ◽  
2021 ◽  
Author(s):  
Si‐Yu Liu ◽  
Qing‐Zhou Zhang ◽  
Min‐Qiang Hu ◽  
Feng‐Xia Li ◽  
Jia‐Miao Fu ◽  
...  
Keyword(s):  
Cyclosporine A ◽  
Cyclophilin A ◽  
Albumin Binding

Clinical factors of cyclosporine A-induced gingival overgrowth and serum cyclophilin A in renal transplant recipients

2013 ◽  
Vol 33 (5) ◽  
pp. 515-520
Author(s):  
Lei JIANG ◽  
Ming-jin GAO ◽  
Jing ZHAO ◽  
Shu-wei ZHAO ◽  
Yun-fu ZHAO
Keyword(s):  
Renal Transplant ◽  
Cyclosporine A ◽  
Cyclophilin A ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Clinical Factors ◽  
Gingival Overgrowth

scholarly journals Human coronavirus NL63 replication is cyclophilin A-dependent and inhibited by non-immunosuppressive cyclosporine A-derivatives including Alisporivir

2014 ◽  
Vol 184 ◽  
pp. 44-53 ◽  
Author(s):  
Javier Carbajo-Lozoya ◽  
Yue Ma-Lauer ◽  
Miroslav Malešević ◽  
Martin Theuerkorn ◽  
Viktoria Kahlert ◽  
...  
Keyword(s):  
Cyclosporine A ◽  
Cyclophilin A ◽  
Human Coronavirus

scholarly journals Treatment of Human Immunodeficiency Virus Type 1 Virions Depleted of Cyclophilin A by Natural Endogenous Reverse Transcription Restores Infectivity

2003 ◽  
Vol 77 (7) ◽  
pp. 4431-4434 ◽  
Author(s):  
Mahfuz Khan ◽  
Minerva Garcia-Barrio ◽  
Michael D. Powell
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Cyclosporine A ◽  
Reverse Transcription ◽  
Cyclophilin A ◽  
Wild Type ◽  
Immunodeficiency Virus ◽  
Binding Loop ◽  
Cypa Binding

ABSTRACT We have previously shown that virions with nef deleted can be restored to wild-type infectivity by treatment to induce natural endogenous reverse transcription (NERT). Since Nef and cyclophilin A (CyPA) appear to act in similar ways on postentry events, we determined whether NERT treatment would restore infectivity to virions depleted of CyPA. Our results show that the infectivity of virions depleted of CyPA by treatment with cyclosporine A could be restored by NERT treatment, while mutants in the CyPA binding loop of capsid could only be partially restored. These results suggest that CyPA is involved in some aspect of the uncoating process.

Cyclosporine A-resistant human immunodeficiency virus type 1 mutants demonstrate that Gag encodes the functional target of cyclophilin A.

1996 ◽  
Vol 70 (8) ◽  
pp. 5170-5176 ◽  
Author(s):  
D Braaten ◽  
C Aberham ◽  
E K Franke ◽  
L Yin ◽  
W Phares ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cyclosporine A ◽  
Cyclophilin A ◽  
Immunodeficiency Virus

Cyclosporine A inhibits hepatitis C virus nonstructural protein 2 through cyclophilin A

Hepatology ◽  
2009 ◽  
Vol 50 (5) ◽  
pp. 1638-1645 ◽  
Author(s):  
Sandra Ciesek ◽  
Eike Steinmann ◽  
Heiner Wedemeyer ◽  
Michael P. Manns ◽  
Johann Neyts ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cyclosporine A ◽  
Nonstructural Protein ◽  
Cyclophilin A ◽  
Nonstructural Protein 2

scholarly journals Association of cyclophilin A with renal brush border membranes: Redistribution by cyclosporine A

2000 ◽  
Vol 57 (4) ◽  
pp. 1590-1598 ◽  
Author(s):  
Michel Demeule ◽  
Alain Laplante ◽  
Arash Sepehr-Araé ◽  
Gérard M. Murphy ◽  
Roland M. Wenger ◽  
...  
Keyword(s):  
Cyclosporine A ◽  
Brush Border ◽  
Cyclophilin A ◽  
Brush Border Membranes ◽  
Renal Brush Border Membranes ◽  
Renal Brush Border

scholarly journals Inhibition of HIV-1 Replication by Cyclosporine A or Related Compounds Correlates with the Ability to Disrupt the Gag–Cyclophilin A Interaction

Virology ◽  
1996 ◽  
Vol 222 (1) ◽  
pp. 279-282 ◽  
Author(s):  
Ettaly Kara Franke ◽  
Jeremy Luban
Keyword(s):  
Cyclosporine A ◽  
Cyclophilin A ◽  
Related Compounds ◽  
Hiv 1

A Cyclophilin A-Independent Capsid Motif Renders HIV-1 Derived Vectors More Efficient at Transducing Human Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5531-5531
Author(s):  
Christina H. Swan ◽  
Udayan Chatterji ◽  
Philippe Gallay ◽  
Bruce E. Torbett
Keyword(s):  
Stem Cells ◽  
Amino Acid ◽  
Hematopoietic Stem Cells ◽  
Binding Site ◽  
Cyclosporine A ◽  
Cyclophilin A ◽  
Human Cells ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Hiv 1

Abstract We recently identified naturally occurring HIV-1 capsid (CA) motifs, which evade both cyclophilin A (CypA)-dependence in human cells and TRIM-5α-CypA (TRIM-Cyp) restriction in owl monkey kidney (OMK) cells (Chatterji, et al. JBC, In press). These HIV-1 capsid motifs contained either one (G89V) or four (V86P/H87Q/I91V/M96I) amino acid substitutions within the CypA binding site, but only the four amino acid mutant was able to bind CypA, yet does not require CypA incorporation to infect human cells. OMK cells are naturally resistant to HIV-1 infection due to TRIM-Cyp, a negative host factor, which efficiently targets incoming wild type HIV-1 capsid and thereby prevents the proper uncoating of the CA core. However, addition of cyclosporine A, which blocks the interaction of CypA and CA, or mutations within the CypA-CA binding site (G89V) yields OMK cells permissive to HIV-1. Interestingly, HIV-1 infection with the V86P/H87Q/I91V/M96I capsid mutant was able to achieve similar levels of infection in OMK cells as does wild type HIV-1 with the addition of cyclosporine A, emphasizing that this motif allows infection despite TRIM-Cyp-CA interactions. Alternatively, the interaction between HIV-1 CA and CypA, is considered as a positive host factor in human cells. It has been proposed that CypA either “protects” the virus from endogenous restriction factors or allows proper CA core uncoating. Human cells lacking CypA or treated with cyclosporine A are highly resistant to infection by wild type HIV-1. Virus is blocked during the early stage of infection, at the pre-reverse transcription step. An important goal of human gene therapy is to efficiently deliver genes to non-dividing or quiescent cells such as hematopoietic stem cells and T-cells, respectively. Improvements on vector design such as self-inactivating LTRs, VSV-G envelope pseudotyping, various viral capsids, and enhancer elements have improved both the safety and efficiency of gene delivery. To identify capsid motifs that enhance transduction, we assessed whether the G89V and V86P/H87Q/I91V/M96I capsid motifs increased transduction efficacy in primary human cells as compared to vectors packaged with wild type HIV-1 gag/pol. Preliminary studies, at low levels of transduction (2000 pg p24 input ~1 MOI) in 293T cells, showed a 3-fold increase in GFP expression using the V86P/H87Q/I91V/M96I-gag/pol packaged vectors as compared to wild type or G89V-gag/pol vectors. Studies with primary PBMC and CD34+ hematopoietic stem cells are underway and will address whether the V86P/H87Q/I91V/M96I capsid motif will allow for greater transduction efficiency for non-cycling, quiescent and/or partially activated cells. Providing a means to enhance uniform vector transduction efficacy should allow for lower levels of vector input during transduction, thereby reducing the probability for insertional mutagenesis.

Structural Similarity of the Binding Sites of Cyclophilin A-Cyclosporine A and FKBP-FK506 Systems

1993 ◽  
Vol 192 (2) ◽  
pp. 912-917 ◽  
Author(s):  
A.I. Denesyuk ◽  
M. Vihinen ◽  
J. Lundell ◽  
V.P. Zavyalov ◽  
T. Korpela
Keyword(s):  
Cyclosporine A ◽  
Binding Sites ◽  
Cyclophilin A ◽  
Structural Similarity
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