E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Cyclophilins and Viruses"

Quicklinks

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 April 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Hengli Tang

Associate Professor, Department of Biological Science, Florida State University, 319 Stadium Dr., Tallahassee, FL 32304, USA
Website | E-Mail
Fax: +850 645 8447
Interests: virus-host cell interactions; antiviral drugs and resistance; cellular cofactors for viral infection; hepatitis C virus; HIV; stem cells and differentiation; cell culture models for viral infection

Special Issue Information

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs).

Keywords

  • hepatitis C virus
  • HIV/retroviruses
  • coronavirus
  • human cytomegalovirus
  • influenza virus
  • TRIM5-Cyp Fusion
  • cyclophilin Inhibitors
  • cyclosporine A
  • alisporivir
  • HIV capsid
  • viral replication
  • drug target
  • cellular cofactor chaperone
  • peptidyl-prolyl isomerase

Published Papers (5 papers)

View options order results:
result details:
Displaying articles 1-5
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle Correlation of Naturally Occurring HIV-1 Resistance to DEB025 with Capsid Amino Acid Polymorphisms
Viruses 2013, 5(3), 981-997; doi:10.3390/v5030981
Received: 1 March 2013 / Revised: 18 March 2013 / Accepted: 20 March 2013 / Published: 22 March 2013
Cited by 7 | PDF Full-text (407 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
DEB025 (alisporivir) is a synthetic cyclosporine with inhibitory activity against human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV). It binds to cyclophilin A (CypA) and blocks essential functions of CypA in the viral replication cycles of both viruses. DEB025 inhibits clinical
[...] Read more.
DEB025 (alisporivir) is a synthetic cyclosporine with inhibitory activity against human immunodeficiency virus type-1 (HIV-1) and hepatitis C virus (HCV). It binds to cyclophilin A (CypA) and blocks essential functions of CypA in the viral replication cycles of both viruses. DEB025 inhibits clinical HIV-1 isolates in vitro and decreases HIV-1 virus load in the majority of patients. HIV-1 isolates being naturally resistant to DEB025 have been detected in vitro and in nonresponder patients. By sequence analysis of their capsid protein (CA) region, two amino acid polymorphisms that correlated with DEB025 resistance were identified: H87Q and I91N, both located in the CypA-binding loop of the CA protein of HIV-1. The H87Q change was by far more abundant than I91N. Additional polymorphisms in the CypA-binding loop (positions 86, 91 and 96), as well as in the N-terminal loop of CA were detected in resistant isolates and are assumed to contribute to the degree of resistance. These amino acid changes may modulate the conformation of the CypA-binding loop of CA in such a way that binding and/or isomerase function of CypA are no longer necessary for virus replication. The resistant HIV-1 isolates thus are CypA-independent. Full article
(This article belongs to the Special Issue Cyclophilins and Viruses)
Open AccessArticle Subtype Specific Differences in NS5A Domain II Reveals Involvement of Proline at Position 310 in Cyclosporine Susceptibility of Hepatitis C Virus
Viruses 2012, 4(12), 3303-3315; doi:10.3390/v4123303
Received: 11 October 2012 / Revised: 17 November 2012 / Accepted: 20 November 2012 / Published: 22 November 2012
Cited by 11 | PDF Full-text (699 KB) | HTML Full-text | XML Full-text
Abstract
Hepatitis C virus (HCV) is susceptible to cyclosporine (CsA) and other cyclophilin (CypA) inhibitors, but the genetic basis of susceptibility is controversial. Whether genetic variation in NS5A alters cell culture susceptibility of HCV to CypA inhibition is unclear. We constructed replicons containing NS5A
[...] Read more.
Hepatitis C virus (HCV) is susceptible to cyclosporine (CsA) and other cyclophilin (CypA) inhibitors, but the genetic basis of susceptibility is controversial. Whether genetic variation in NS5A alters cell culture susceptibility of HCV to CypA inhibition is unclear. We constructed replicons containing NS5A chimeras from genotypes 1a, 2a and 4a to test how variation in carboxy terminal regions of NS5A altered the genotype 1b CsA susceptibility. All chimeric replicons including genotype 1b Con1LN-wt replicon exhibited some cell culture sensitivity to CsA with genotype 4a being most sensitive and 1a the least. The CypA binding pattern of truncated NS5A genotypes correlated with the susceptibility of these replicons to CsA. The Con1LN-wt replicon showed increased susceptibility towards CsA when proline at position 310P was mutated to either threonine or alanine. Furthermore, a 15 amino acid long peptide fused N terminally to GFP coding sequences confirmed involvement of proline at 310 in CypA binding. Our findings are consistent with CypA acting on multiple prolines outside of the previously identified CypA binding sites. These results suggest multiple specific genetic variants between genotype 1a and 1b in the C-terminus of NS5A alter the CsA susceptibility of replicons, and some variants may oppose the effects of others. Full article
(This article belongs to the Special Issue Cyclophilins and Viruses)

Review

Jump to: Research

Open AccessReview Cyclophilins as Modulators of Viral Replication
Viruses 2013, 5(7), 1684-1701; doi:10.3390/v5071684
Received: 22 May 2013 / Revised: 26 June 2013 / Accepted: 3 July 2013 / Published: 11 July 2013
Cited by 23 | PDF Full-text (223 KB) | HTML Full-text | XML Full-text
Abstract
Cyclophilins are peptidyl‐prolyl cis/trans isomerases important in the proper folding of certain proteins. Mounting evidence supports varied roles of cyclophilins, either positive or negative, in the life cycles of diverse viruses, but the nature and mechanisms of these roles are yet to be
[...] Read more.
Cyclophilins are peptidyl‐prolyl cis/trans isomerases important in the proper folding of certain proteins. Mounting evidence supports varied roles of cyclophilins, either positive or negative, in the life cycles of diverse viruses, but the nature and mechanisms of these roles are yet to be defined. The potential for cyclophilins to serve as a drug target for antiviral therapy is evidenced by the success of non-immunosuppressive cyclophilin inhibitors (CPIs), including Alisporivir, in clinical trials targeting hepatitis C virus infection. In addition, as cyclophilins are implicated in the predisposition to, or severity of, various diseases, the ability to specifically and effectively modulate their function will prove increasingly useful for disease intervention. In this review, we will summarize the evidence of cyclophilins as key mediators of viral infection and prospective drug targets. Full article
(This article belongs to the Special Issue Cyclophilins and Viruses)
Open AccessReview Suppression of Coronavirus Replication by Cyclophilin Inhibitors
Viruses 2013, 5(5), 1250-1260; doi:10.3390/v5051250
Received: 18 March 2013 / Revised: 2 May 2013 / Accepted: 8 May 2013 / Published: 22 May 2013
Cited by 7 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or
[...] Read more.
Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS), feline infectious peritonitis (FIP), mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA), could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication. Full article
(This article belongs to the Special Issue Cyclophilins and Viruses)
Open AccessReview Insights into the Roles of Cyclophilin A During Influenza Virus Infection
Viruses 2013, 5(1), 182-191; doi:10.3390/v5010182
Received: 22 November 2012 / Revised: 22 December 2012 / Accepted: 9 January 2013 / Published: 15 January 2013
Cited by 12 | PDF Full-text (274 KB) | HTML Full-text | XML Full-text
Abstract
Cyclophilin A (CypA) is the main member of the immunophilin superfamily that has peptidyl-prolyl cis-trans isomerase activity. CypA participates in protein folding, cell signaling, inflammation and tumorigenesis. Further, CypA plays critical roles in the replication of several viruses. Upon influenza virus infection, CypA
[...] Read more.
Cyclophilin A (CypA) is the main member of the immunophilin superfamily that has peptidyl-prolyl cis-trans isomerase activity. CypA participates in protein folding, cell signaling, inflammation and tumorigenesis. Further, CypA plays critical roles in the replication of several viruses. Upon influenza virus infection, CypA inhibits viral replication by interacting with the M1 protein. In addition, CypA is incorporated into the influenza virus virions. Finally, Cyclosporin A (CsA), the main inhibitor of CypA, inhibits influenza virus replication through CypA-dependent and -independent pathways. This review briefly summarizes recent advances in understanding the roles of CypA during influenza virus infection. Full article
(This article belongs to the Special Issue Cyclophilins and Viruses)

Journal Contact

MDPI AG
Viruses Editorial Office
St. Alban-Anlage 66, 4052 Basel, Switzerland
viruses@mdpi.com
Tel. +41 61 683 77 34
Fax: +41 61 302 89 18
Editorial Board
Contact Details Submit to Viruses
Back to Top